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Medicine, Nursing and Health Sciences
School of Biomedical Sciences
Annual Report 2011
Australia
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www.med.monash.edu/sobs
Contents
3
From the Head of School
4
Year in Review: Research
5
Year in Review: Awards
8
Year in Review: Events
10Overview
12Cancer
20
Cardiovascular Disease
26
Developmental Biology
36
Drug Design
40Immunology
School of Biomedical Sciences Annual Report 2011
Editor
Vicki Burkitt
Design, photography and production
44
Immunology and Stem Cells
50
Infectious Diseases
60
Medical Imaging and Radiation Sciences
62Neuroscience
70Obesity
MNHS Multimedia Services
76
Structural Biology
Communications contacts
86
Facilities and Centres
94
Grants and Funding
Telephone:+61 3 9902 9407
Email:
[email protected]
Web:
www.med.monash.edu/sobs
Mail
School of Biomedical Sciences
Building 77
Monash University
Clayton, Victoria 3800
Australia
Cover image: Lipid droplets containing fat (red) in an
adipocyte (fat cell). The protein adipose triglyceride
lipase (green), which breaks down fat, is also shown.
Image: Joanne Pagon.
100Education
108
Postgraduate Research
112Administration
116
Research Publications
129
Research Staff Index
From the Head of School
I congratulate all members of the School
of Biomedical Sciences for another
successful year in 2011. Researchers
in the School were awarded $49 million
of research income from national and
international funding sources, and our
scientists published 484 publications,
38 in high impact journals, including:
Nature, Nature Biotechnology, Cancer
Cell, Nature Immunology, Immunity and
Nature Methods.
Professor Christina Mitchell
Professor Jamie Rossjohn had a stellar year. He was awarded
a 2011 NHMRC Australia Fellowship and will receive $4 million
over five years to further his immunity research. He was also a
joint recipient of the prestigious Roche Organ Transplantation
Research Foundation Recognition Prize.
Professor Rob Pike has relinquished his role as Head of
Biochemistry and Molecular Biology, and I thank him for his
outstanding contribution over the last five years. He will be
replaced by Professor Rod Devenish in an acting capacity
until a new Head is appointed.
Associate Professor Martin Lackmann’s cancer research project
made the NHMRC top 10 grants for 2010. After his longstanding
work on the role of Eph receptors in cancer, a candidate drug is
now being tested for safety and anti-tumour effects in leukaemia
patients in hospitals in Australia and the US.
Congratulations go to Professor Wayne Hodgson, who is the
Faculty’s new Deputy Dean (Education). He has therefore stepped
down from his role as co-Head of Pharmacology.
Professor Michael Cowley, Director of the Monash Obesity and
Diabetes Institute, added another accolade to his list. The obesity
researcher was elected a Fellow of the Australian Academy of
Technological Sciences and Engineering.
Structural biology infrastructure at Monash will be boosted by
the establishment of The Clive and Vera Ramaciotti Centre for
Structural Cryo-Electron Microscopy. A group led by Professors
James Whisstock and Ian Smith, and including scientists from
Walter and Eliza Hall Institute, the University of Melbourne, La
Trobe University, Burnet Institute and Peter MacCallum Cancer
Centre, received $1 million from Ramaciotti Foundations and
$640,000 from the Australian Research Council.
The School continues to promote excellence in its teaching
programs. Highlights for the year include Dr Richard Loiacono
receiving the Dean’s Award for Excellence in Education (Quality)
and the introduction of Biomedical Science Scholars and
Biomedical Science Advanced Honours programs. In these
programs, high-achieving students are matched with academic
mentors within the School and attend research platform tours
and seminars.
We welcomed many new staff to the School: in particular,
Professor Christian Doerig, malaria researcher and our new
Head of Microbiology; former Governor of Victoria, Professor
David de Kretser, who continues his research on fertility; obesity
researchers Professors David Spanswick and Mark Sleeman;
neurodegenerative disease researcher Professor Zhi-Cheng Xiao;
and Dr Jose Polo, a stem cell scientist.
On a personal note, in October 2011 I took up the role of Dean
of Medicine, Nursing and Health Sciences after a five-year term
as Head of School. I am pleased to announce that following
a comprehensive recruitment process Professor John Carroll
from University College London has been appointed as my
replacement. John is an eminent scientist and leader who will
bring a wealth of experience to the School. The Deputy Head of
School Professor Phillip Bird will act as Head until John joins us in
September 2012.
I thank the School’s Executive team including the Department
Heads for their continuing support and leadership. I am
particularly grateful to the School Manager Doug McGregor and
his team, who keep the School functioning at a high level. I also
wish to thank staff in the HR and finance service hubs for their
work in 2011.
Finally, I gratefully acknowledge the contribution of colleagues in
the Monash senior leadership group: particularly, former Dean of
Medicine Professor Steve Wesselingh, Deputy Vice-Chancellor
(Research) Professor Edwina Cornish, Deputy Vice-Chancellor
(Education) Adam Shoemaker, and Vice-Chancellor Professor
Ed Byrne.
Professor Christina Mitchell
Dean, Medicine, Nursing and Health Sciences
Professor John Davies stepped down as Head of Microbiology in
preparation for retirement in 2013. As Head of Department and
former Deputy Head of School he has provided significant and
longstanding service for which we are all grateful.
3
Annual Report 2011
Year in Review
Year in Review: Awards
Year in Review: Research
Unravelling the natural killer within us
Making heart cells from stem cells
A team of scientists co-led by Professor Jamie Rossjohn
(Monash University) and Associate Professor Andrew Brooks
(University of Melbourne) has provided detailed structural insight
of how an innate immune cell receptor called KIR3DL binds to
its ligand HLA-B57. The KIR family of proteins are produced by
natural killer cells, which remove tumours and virus-infected cells,
including HIV. These findings, by J. Vivian et al., represent the first
study to determine the molecular basis of KIR3DL1 recognition
(Nature, 2011. Oct 23; 479 (7373): 401-405).
Professors Ed Stanley and Andrew Elefanty, together with national
and international collaborators, have successfully and reliably
generated human heart muscle cells from genetically modified
human embryonic stem cells expressing a fluorescent marker
under the control of the important cardiac gene NKX2-5.
They have also used these cells to identify new cardiac cell
surface proteins. These findings will allow researchers to use drug
screening and tissue engineering strategies to develop candidate
treatments for heart disease
(Nature Methods, 2011. 8(12): 1037-1040.
Nature Biotechnology, 2011. 29(11): 1011-1018).
Recognition of ß–linked self glycolipids
mediated by natural killer T cell activation
A team of scientists co-led by Professor Jamie Rossjohn
(Monash University), Professor Dale Godfrey (University of
Melbourne) and Associate Professor Laurent Gapin (National
Jewish Health and University of Colorado School of Medicine)
has shown how Natural killer T (NKT) cells recognise self-antigens
is similar to how microbial molecules are recognised. Here
they suggest a mechanism for NKT autoimmunity, where selfantigens are processed to resemble the conformation of foreign
microbial antigens. NKT cells are linked to microbial immunity,
autoimmunity, allergy and cancer, and represent an important
immunotherapeutic target with clinical potential
(Nature Immunology, 2011. Jul 31; 12(9): 827-833).
4
Structure of KIR3DL1 (magenta) in complex with HLA-B*57:01. The HLA heavy chain is coloured
green, the light chain is cyan, and the peptide presented by the HLA is orange.
Metabolic proteins and obesity
An international team of scientists, led by Professor Tony
Tiganis, has established for the first time how protein tyrosine
phosphatase, or TCPTP, regulates the hormone leptin, which
plays a key role in body weight maintenance and reproductive
health. They have also shown that increased levels of TCTP in the
brain region called the hypothalamus results in leptin resistance
and morbid obesity. These findings help explain how obesity
progresses, providing clues for future treatments
(Cell Metabolism, 2011. Nov 2; 14(5): 684-699).
Cryo-electron microscopy centre
for Victoria
Immunity and transplantation research
recognised
Victorian scientists are one step closer to having a dedicated
structural cryo-electron microscopy facility, with $1 million
committed by Ramaciotti Foundations and $640,000 from the
Australian Research Council. The Clive and Vera Ramaciotti
Centre for Structural Cryo-Electron Microscopy, which will be
built at Monash University, will help scientists answer difficult
structural biology questions. The centre, to be led by Professors
James Whisstock and Ian Smith (School of Biomedical Sciences),
and Associate Professor Mike Lawrence (Walter and Eliza Hall
Institute), will also include collaborators from the University
of Melbourne, La Trobe University, Burnet Institute and Peter
MacCallum Cancer Centre.
Professor Rossjohn, from the Department of Biochemistry and
Molecular Biology, was awarded a 2011 NHMRC Australia
Fellowship. He will receive $4.0 million of funding over five years
to further his research in immunity. Also, Professor Rossjohn
and Dr James McCluskey, from the University of Melbourne, are
joint recipients of the Roche Organ Transplantation Research
Foundation Recognition Prize. Professor Rossjohn received
a plaque at a ceremony in Philadelphia on 30 April. The two
scientists had previously been awarded a ROTRF research grant
worth $300,000 Swiss Francs over three years.
Obesity expert an Australian academy
fellow
Associate Professor’s Martin Lackmann’s cancer research project
was named one of the ten best research projects in 2010 by
NHMRC. The scientist from the Department of Biochemistry
and Molecular Biology studies Eph receptors, proteins that play
a critical role in the assembly of healthy tissues and organs,
and tumours. He has developed an antibody called KB004 that
recognises a specific Eph receptor on the surface of leukaemic
cells and on cells lining tumour blood vessels. This candidate
drug is being tested for safety and anti-tumour effects in
leukaemia patients in hospitals in Australia and the US.
Professor Michael Cowley, from the Department of Physiology
and Director of the Monash Obesity and Diabetes Institute, was
elected a Fellow of the Australian Academy of Technological
Sciences and Engineering. Professor Cowley joins other
technology and research leaders at Monash, including:
Dr Alan Finkel AM, Chancellor; Professor Edwina Cornish,
Senior Deputy Vice-Chancellor and DVC (Research); and
Professor Rod Hill, Pro-Vice Chancellor (Industry Engagement
and Commercialisation).
Cancer research project makes top ten
Green fluorescent protein expression in contracting human heart muscle cells grown from
genetically modified human embryonic stem cells.
Ramaciotti Biomedical Research awardees with Perpetual and Ramaciotti Foundation
representatives. Image: Nic Long.
2011 NHMRC Australia Fellow, Professor Jamie Rossjohn (right) with The Hon Mark Butler MP.
Image: NHMRC.
PTP1B and TCPTP decrease leptin signalling in obesity.
Professor Michael Cowley (right) receives his Fellowship certificate from Professor Robin
Batterham, ATSE President. Image: ATSE.
Associate Professor Martin Lackmann (left) with The Hon Mark Butler MP. Image: NHMRC.
5
Annual Report 2011
Year in Review
Year in Review: Awards
Infectious diseases award for Monash
physician and researcher
When images take centre stage
Reproductive biologists in the spotlight
Dr Ian Smyth, from the Departments of Anatomy and
Developmental Biology, and Biochemistry and Molecular Biology,
and Dr Kieran Short, from the Department of Biochemistry and
Molecular Biology, both won 2011 Wellcome Trust image awards
for their stunning medical images. They each received £200 and
a trophy. Also, Dr Ian Smyth was third-placed in the 2011 New
Scientist Eureka Prize for science photography. He received
$2000 prize money for his digital image showing how the fetal
lung of a mouse branches to form airways.
Professors Iain Clarke, Head of the Department of Physiology,
and Moira O’Bryan, from the Department of Anatomy and
Developmental Biology, were appointed fellows of the Society
for Reproductive Biology at the 2011 Annual Society for
Reproductive Biology meeting, in Cairns. Also at the same
conference, Dr Jeremy Smith, from the Department of Physiology,
was the joint winner of the 2011 Newcastle Reproduction
Emerging Research Leader Award, together with Associate
Professor Stephen Tong from the University of Melbourne.
Amgen award for stem cell research
Australian Group of Eight fellowship
supports international collaboration
Dean’s awards for research and education
Associate Professor Sharon Ricardo from the Monash
Immunology and Stem Cell Laboratories received the Amgen
Best Basic Science Award at the Australian and New Zealand
Society of Nephrology meeting for her research on the generation
of stem cells from patients with kidney disease. She received a
cash prize of $3,300 to develop patient-specific stem cell lines for
disease modelling and targeted drug treatments. Award finalists
were selected by abstract peer review prior to the meeting and
awards were judged on presentation and science by independent
judging panels.
Dr Branka Jelicic, from the Rudjer Boskovic Institute in Zagreb,
Croatia, received an Australian Group of Eight fellowship to
work with Dr Ana Traven at the Department of Biochemistry and
Molecular Biology. Dr Jelicic studied how the fungal pathogen
Candida albicans, which kills patients in hospitals, forms complex,
highly drug-resistant structures called biofilms. During her time
here, Dr Jelicic authored two manuscripts together with
Dr Traven, including a paper in press in the prestigious journal
PLoS Genetics. The fellowship is worth $20,000 AUSD and
provides support for a six-month visit.
Dr Anton Peleg, recipient of the Frank Fenner Award for Advanced Research in Infectious Diseases.
Drs Ian Smyth (left) and Kieran Short with a Wellcome award-winning image.
Dr Jeremy Smith (left), joint winner of the 2011 Newcastle Reproduction Emerging
Research Leader Award. Image: Society for Reproductive Biology.
Victoria Hewitt, Adam J. Berry Memorial Fund recipient.
Associate Professor Sharon Ricardo.
Dr Branka Jelicic, Australian Group of Eight University fellowship recipient.
Dean’s Award winners: Dr Stephanie Gras (left) and Professor David Jans.
Anthony Koelmeyer award recipients. From left to right: Jeffrey Moore, Sarah Haas Lockie
and Andrew Clarke.
Dr Anton Peleg received the Frank Fenner Award for Advanced
Research in Infectious Diseases at the Australasian Society of
Infectious Diseases Annual Scientific Meeting, in Lorne, Victoria.
The physician and scientist from the Department of Microbiology
was recognised for his pioneering infectious diseases research on
the hospital-acquired pathogens Acinetobacter baumannii and
Staphylococcus aureus, and infections in immunocompromised
patients. Dr Peleg received a certificate and $5,000. He also
presented a lecture.
6
Year in Review: Awards
Scientists from the Department of Biochemistry and Molecular
Biology received Dean’s Awards for Excellence in Research from
former Dean Professor Steve Wesselingh. Dr Stephanie Gras,
who studies how the T cell receptor recognises harmful viruses,
received an early career award jointly with Dr Kate Hoy from the
School of Psychology and Psychiatry. Professor David Jans,
who studies how proteins from Dengue, rabies and respiratory
syncitial viruses move into and out of the cell nucleus to evade
immune responses, received a distinguished career award.
Also, Dr Richard Loiacono from the Department of Pharmacology
received the Dean’s Award for Excellence in Education (Quality).
PhD student travels for mitochondrial
research
PhD student Victoria Hewitt received funding from the Australian
Academy of Sciences, National Institutes of Health and the
2011 Adam J Berry Memorial Fund to spend three months in
the laboratory of Dr Susan Buchanan, a leader in membrane
protein crystallography at the National Institute of Diabetes and
Kidney Diseases, in the US. Victoria, who conducts mitochondrial
research at the Department of Biochemistry and Molecular
Biology, learned new techniques in protein biochemistry and also
set up a research partnership between the two laboratories. The
international program was established in memory of Adam Berry,
a young Australian scientist.
Flying high for science
Three PhD students scored inaugural Anthony Koelmeyer
International PhD Excellence awards. They received $1,500 each
towards conference costs and research training in overseas
laboratories. Andrew Clarke, from the Department of Biochemistry
and Molecular Biology, attended an immunology conference in
Greece and visited labs in England, Scotland and Wales. Sarah
Haas Lockie, from the Department of Physiology, attended a
Society for Ingestive Behaviour meeting in Florida, and visited labs
in Michigan and Ohio, US. Jeffrey Moore, from the Department of
Pharmacology, attended the American Heart Association’s High
Blood Pressure Research Scientific Sessions in Florida and visited
colleagues at Emory University, in Atlanta.
7
Annual Report 2011
Year in Review: Events
Big 5-0 for biochemistry teaching
and research
Past and present members of the Department of Biochemistry
and Molecular Biology gathered together to celebrate 50
years at Monash University at the Melbourne Convention and
Exhibition Centre. During the mini-symposium that marked this
event, former Heads of Department Professors Robert Pike and
Christina Mitchell spoke about the development of biochemistry
here from its early beginnings to today, and Monash alumnus
Professor John Mattick AO discussed the role of non-coding
RNAs in the evolution and development of complex organisms.
Guests included former academic and professional staff, and
colleagues from other departments and institutes in Melbourne.
Golden anniversary for anatomy teaching
and research
The Department of Anatomy and Developmental Biology also
celebrated their 50th anniversary at the School of Biomedical
Sciences. Current and former staff and alumni discussed
directions in research and teaching during this period, as well
as plans for the future. Before and after the speeches, there were
opportunities for guests to tour the anatomy teaching, research
and histology laboratories and mingle informally.
Biochemistry anniversary guests. From left to right: Associate Professor Merrill Rowley, Dr Senga
Whittingham and Dr Marie-Paule van Damme. Image: Phillip Nagley.
8
Guests mingling at the anatomy anniversary event.
Public forum to raise stem cell awareness
As part of Stem Cell Awareness Day, Monash Immunology and
Stem Cell Laboratories hosted free public seminars at BMW
Edge, at Federation Square. Research leaders discussed stem
cell therapy approaches for osteoarthritis and neurological
disorders, including: Multiple Sclerosis, spinal cord injury and
Alzheimer’s Diseases. Guest speakers included MISCL director
Professor Richard Boyd; industry partner and Mesoblast CEO
Professor Silviu Itescu; stem cell researchers Professor Andrew
Elefanty, Professor Ed Stanley, Professor Colin Poulton and
Dr Martin Short; neurosurgeons Professor Jeff Rosenfeld and
Dr Tony Goldschlager; and North Melbourne Football Club doctor,
Dr Dan Bates.
The end of antibiotics public lecture
Among the public outreach programs for the year, the ARC
Centre of Excellence in Structural and Functional Microbial
Genomics organised a public lecture at BMW Edge, at Federation
Square, as part of National Science Week. Dr Paul Johnson
from Austin Health presented the lecture: The End of Antibiotics,
a topical theme given the rise of antibiotic resistant bacteria
worldwide. The lecture was followed by a panel discussion
comprising staff from the Monash Department of Microbiology.
Dr Martin Short speaking at Stem Cell Awareness Day.
Overview:
We conduct research within
these departments:
>> Anatomy and Developmental Biology
>> Biochemistry and Molecular Biology
>> Immunology Clayton
>> Medical Imaging and Radiation Sciences
>> Microbiology
>> Monash Immunology and
Stem Cell Laboratories
>> Pharmacology
>> Physiology
We study:
>> Cancer
>> Cardiovascular Disease
>> Developmental Biology
>> Drug Design
>> Immunology
>> Infectious Diseases
>> Medical Imaging and Radiation Sciences
>> Neuroscience
>> Obesity
>> Stem Cells
>> Structural Biology
Cancer
One in three men and one in four
women in Australia will develop
cancer by the age of 75*
>> H
ow do tumours develop and which
proteins are involved?
>> H
ow do cancer-susceptible cells respond
to environmental stresses?
>> W
hat role do stem cells play in breast
and prostate cancer?
>> What is the role of estrogen in
prostate cancer?
>> How do bacteria cause stomach cancer?
>> H
ow do cancer cells invade tissues
and spread?
>> W
hat biomarkers can we use to detect
early-stage colorectal cancer?
>> How can we develop new treatments that
target tumours and spare healthy tissues?
*Cancer Australia
www.canceraustralia.gov.au/affected-cancer/cancer-australia
Complex arrangement of prostatic stromal cells in experimental models
of prostate cancer. Image: Ms Hong Wang.
12
Annual Report 2011
Cancer
Microbial Oncogenesis Laboratory
Infection with the rod-shaped bacteria
Helicobacter pylori results in peptic ulcers.
Helicobacter pylori-infected persons have
a 2- to 8-fold increased risk of developing
gastric cancer compared with uninfected
individuals. Our laboratory uses Helicobacter
pylori infection as a model system to study
how bacteria can infect target cells and
cause them to become malignant.
Research Fellow
PhD Students
We investigate the molecular mechanisms by which
Helicobacter pylori 'inject' cancer-inducing proteins into
stomach cells and how host receptor proteins such as
integrins are co-opted by the bacteria to participate in
this process.
Honours Students
We also hope to understand how Helicobacter pylori
influence host signalling pathways during chronic
inflammation and gain novel insights into how healthy
tissue can become cancerous during chronic infection
and inflammation.
Dr Rebecca Gorrell
Research Assistant
Ms Jye Guan
Ms Paige Everingham
Mr Thai Son Nguyen
Ms Mona Anoushiravani Tafreshi
Mr Abolghasem Tohidpour
Mr Nicholas Clark
Ms Suzzane Huang
Mr Samuel Palframan
Dr Terry Kwok-Schuelein
NHMRC Equipment Grant
Faculty Strategic Grant
• Structural analysis of the Helicobacter pylori virulence
protein CagL for development of novel therapeutics
(2011–2012).
Research Fellows
Dr Degu Abebe
Dr Rae Farnsworth
Dr Nadia Harun
Dr Peter Janes
Dr April Tan
Dr Mary Vail
Research Assistants
Mr Chanly Chheang
Ms Aileen Hea
Ms Linda Hii
Ms Carmen Llerena
PhD Students
• Helicobacter pylori VacA toxin: modulation of human
mitochondrial function by a bacterial pathogen
(2011–2015).
Ms Lakmali Atapattu
Ms Eva Nievergall
Ms Catherine To
Dr Darius Lane
PhD Students
Mr Po-Hua Chang
Ms Samantha Fernandes
Ms Megan Kerr
Masters Students
Ms Joannah Cane
Ms Mun Joo Chuei
Mr Samuel Thompson
We are now developing candidate anti-cancer therapeutics
that can detect and destroy tumour cells and tumour blood
vessels in cancer patients. Our current drug candidate is a
monoclonal antibody that recognises a specific Eph receptor
on the surface of leukaemic cells and on cells lining tumour
blood vessels. As this antibody attacks these cancerous
cells and disrupts supporting blood vessels but not healthy
tissues, this molecule is now being tested for safety and
anti-tumour effects in leukaemia patients in hospitals in the
US and Australia.
Cancer Australia Priority-driven Collaborative Cancer
Research Scheme
• Preclinical and clinical evaluation of an antibody targeting
prostate carcinoma, Lackmann/Scott/Boyd (2008–2011).
KaloBios Pharmaceuticals Inc. Translational Research
and In-licensing Agreement and Research Support
• Molecular engineering of therapeutics targeting
disease-modulating cell surface receptors, Lackmann/
Scott/Boyd (2010–2012).
Awards and Achievements
Associate Professor Martin Lackmann
• Cancer research project awarded NHMRC Top Ten
by the Hon Mark Butler MP, February 2011.
• Treatment of first leukemia patient at the Moffit Cancer
Centre (Florida, US) with an anti-cancer antibody
developed in the Lackmann lab, March 2011.
• Colorectal cancer-molecular basis to targeted
therapeutics, Burgess/Scott/Simpson/Garrett/
Lackmann/Ernst/Ramsey/Heath/Caruso (2009–2013).
Human Frontiers Science Program Organisation
(Strasbourg, France)
• The molecular dynamics and imaging of Eph receptorguided cell positioning in tissue assembly, Pawson/Neel/
Lackmann/Bastiaens (2009–2011).
Intravital imaging of tumour vessels. Tumour vessels stained with
green fluorescent dye (vessel wall) and red fluorescent quantum dots
(blood), showing vessel leakiness. Image: Dr Mary Vail.
Dr Alfons Lawen
www.med.monash.edu.au/biochem/staff/lackmann.html
Iron is important for cellular survival: without
it, every cell will die. In its physiological form,
extracellular iron is complexed by chelators,
molecules that bind to metallic ions.
Research Fellow
We are interested in proteins that reside on the surface of
tumour cells, and control their interaction with surrounding
cells and tissues. Of particular interest in cancer are a family
of proteins called Eph receptors, which play a critical role
in the assembly of healthy tissues and organs and tumours.
We combine molecular engineering with imaging techniques
to study fluorescently-tagged cells in intact tumours, and
record the activity of Eph proteins and their partners on the
cell surface.
Associate Professor Martin Lackmann
NHMRC Program Grant
Rod-shaped Helicobacter pylori (blue) interacting with gastric epithelial
cells (yellow).
www.med.monash.edu.au/biochem/staff/kwok-schuelein.html
Plasma Membrane Electron Transport
and Iron Uptake
We study how tumours invade tissues by
recruiting new blood vessels and supporting
connective tissue. These insights help us
develop reagents that may lead to new
anti-cancer therapies.
• Tecnai Spirit 120kV Transmission Electron Microscope
(2011–2015).
NHMRC Project Grants
• Roles of integrin receptors and the Helicobacter pylori
protein CagL in gastritis and gastric cancer (2009–2012).
Protein Interaction and Cancer Research
The most important iron chelators are the protein transferrin
and the metabolite citrate. In order for iron from iron citrate
to be taken up by a cell, it has to be first reduced from iron
(III) to iron (II). For this reduction to occur, the electrons must
be supplied from inside the cell. Our lab’s main interest lies
in understanding how cells transport electrons across the
plasma membrane.
We have analysed the cellular uptake of iron from iron citrate
(Fe3+-Cit) in detail, and found that vitamin C is needed to
reduce iron and to take it up. Cells actively export reduced
vitamin C (ascorbate, Asc) for this purpose (in astrocytes
this process is regulated by neurotransmitters) and take up
oxidised vitamin C (dehydroscorbic acid, DHA). The cells
then reduce it back to ascorbate and release it for further
iron reduction (see figure). In this way, vitamin C supplies
electrons for this important reaction and the subsequent
uptake of iron.
Non-transferrin iron reduction and uptake are regulated by
transmembrane ascorbate cycling in K562 cells.
www.med.monash.edu.au/biochem/staff/lawen.html
14
15
Annual Report 2011
Cancer
Intracellular Signalling and Cancer
Scientific Executive
Assistant
Dr Jelena Becanovic
Research Fellows
Dr Michele Davies
Dr Jennifer Dyson
Dr Sandra Feeney
Dr Rajendra Gurung
Dr Meagan McGrath
Dr Lisa Ooms
Dr Parvin Rahman
Dr Absorn Sriritana
Cancer Council
Research Fellow
Dr Meredith Layton
Research Assistant
Ms Katherine Roan
PhD Students
Ms Micka Bertucci
Ms Sarah Conduit
Ms Colleen D’Arcy
Ms Sandra Hakim
Mr Jordan Kane
Ms Dharini Kethesparan
Ms Tina Liu
Ms Parvin Rahman
Ms Natalie Rynkiewicz
Dr David Sheffield
Mr David Vuong
Mr Brendan Wilding
Honours Students
Mr Matthew Eramo
Ms Sruti Pillai
Ms Hannah Ring
Professor Christina Mitchell
Head of School (to September 2011)
Dean (from October 2011)
Our major focus is to identify and characterise
novel genes and proteins that regulate cell
proliferation, death, migration and invasion.
ARC Discovery Project Grant
We study lipid phosphatases and adaptor proteins, which
inhibit signalling in the phosphoinositide 3-kinase (PI3K)
pathway. These lipid phosphatases are either expressed
at high or low levels in tumours, including breast, prostate
and cervical cancers. Our team investigates how these lipid
phosphatases regulate cancer cell growth, proliferation and/
or cell death. Cell motility and invasion are tightly regulated
to prevent the spread or metastasis of cancer cells from one
tissue to another. We are examining how lipid phosphatases
regulate cancer metastasis.
FSHD Global Research Foundation
In addition, we are investigating one of the kinases in the
PI3K pathway, which is mutated and activated in 20–30%
of breast, colon and endometrial tumours. Understanding
how mutation leads to activation will aid in the design of
strategies to switch off this pathway.
Cell Stress Response Laboratory
We study how cells that are susceptible to
cancer and neurodegenerative diseases
respond to different environmental stresses.
• Regulation of neurite outgrowth by an inhibitor of PI3K
signalling, Mitchell (2011–2013).
• Investigation into the role of FHL1, calcineurin and NFAT
in reducing muscle wasting in Fascioscapulohumeral
Muscular Dystrophy (2008-2011).
Muscular Dystrophy Association of USA
• The role of FHL1 in regulating skeletal muscle mass and
regeneration in Duchenne Muscular Dystrophy, Mitchell
(2008–2011).
Research Fellows
Mr Gavin Higgins
Ms Heling Ng
Awards and Achievements
Professor Christina Mitchell
• Appointed Monash Dean of Medicine, Nursing
and Health Sciences, October 2011.
NHMRC Project Grant
• Mitochondria: Molecular and cellular insights into their
diverse contributions to neuronal injury, Beart/Nagley
(2008–2011).
NHMRC Project Grants
• Characterisation of a novel regulator of angiogenesis,
Mitchell (2011–2013).
Composite death outcomes in mammalian cells. The death
outcomes may show a range of properties depending on what cells
look like and what occurs biochemically to drive cells to die. After a
stroke, some stressed nerve cells undergo alternative forms of cell death
called programmed necrosis and autophagic death. These types of cell
death differ from apoptosis, the ‘standard’ controlled death process, or
unregulated necrosis that is a rapid and messy destruction of cells.
www.med.monash.edu.au/biochem/staff/nagley.html
• Characterisation of a novel PI3-kinase signal terminating
enzyme in breast cancer, Mitchell (2011–2013).
• Identification of the molecular mechanisms by which
mutations in FHL1 lead to protein misfolding and skeletal
muscle disease, Mitchell/McGrath (2011–2013).
Clinical Biomarker Discovery and Validation
• Role of the 72 kDa 5-phosphatase in human diseases,
Mitchell/ Smyth/Dyson (2010–2012).
• MTMR4, regulator of PtdIns(3)P, Mitchell/Nandurkar
(2009–2011).
We are interested in the processes that determine the
fate of these stressed cells – whether they survive or die
– and how we can develop strategies to prevent or treat
diseases. In 2011, we studied several cellular models
of neurodegenerative diseases in neuronal cells. We
characterised the death responses in primary cultured
neurones (as a model of stroke) subjected to a range of
stresses that occur in the acutely damaged brain. We also
analysed the death responses in a motor neurone-like cell
line (as a model of motor neurone disease) where protein
aggregation has occurred. We collaborated with Professors
Phil Beart and Mal Horne at Florey Neurosciences Institute;
and Dr Julie Atkin at La Trobe University.
Also, as part of the ARC Centre of Excellence on Structural
and Functional Microbial Genomics, we are working with
Dr Ashley Mansell at Monash Institute of Medical Research
to uncover the role of a novel mitochondrial protein involved
in the cell’s defence against viral infection.
Our group also studies the role of the Four and Half LIM
(FHL) family proteins in skeletal muscle and cardiac muscle
function. Mutations in these proteins cause muscle disease
in humans, leading to muscle weakness.
• Role of the inositol polyphosphate 4-phosphatase type 2
in human breast cancer, Mitchell/McLean (2010–2012).
Professor Phillip Nagley
We develop, validate and measure novel
biomarkers for the early detection and
surveillance of colorectal cancer (CRC),
which represents almost 10 per cent of
cancers worldwide and is the second highest
cause of cancer-related death in Australia.
INPP4B is expressed in luminal epithelial cells (brown staining) in normal
human mammary tissue. Loss of INPP4B expression is a marker of an
aggressive subtype of breast cancer.
www.med.monash.edu.au/biochem/staff/mitchell.html
Research Fellows
Dr Robert Goode
Dr Zon Weng Lai
B. Med. Sci Student
Mr Jason Phung
Unfortunately, 30–50 per cent of CRC patients present with
advanced metastastic disease when prognosis is poor (five
year survival <10 per cent). There is therefore an urgent need
to develop more reliable, sensitive and specific screening
tests that detect CRC at the early stages when therapy is
most likely to be effective (five year survival >90 per cent). We
believe that tumour related products are shed into the faeces
which therefore represents a potential source of protein
biomarkers that indicate the presence of this cancer.
Professor Ed Nice
DIIRD Grant
• Proof of concept study to establish biomarker
translational development in Victoria, Nice/Simpson/
Fox/Thompson/Barlow (2009–2010).
Cancer Council of New South Wales
• A colorectal cancer 'Interactome' paradigm that
influences patient survival, Baker/Nice (2010–2012).
Using state-of-the-art mass spectrometry, we have generated
a library of over 1500 colorectal cancer-related peptides
present in human faeces. We are now developing and
validating sensitive and specific quantitative assays
to assess panels of candidate biomarkers to successfully
detect and monitor colorectal disease.
NHMRC Project Grants
• Colorectal cancer membrane protein interactomics,
Baker/Nice (2011–2013).
• Quantitative proteomic analysis of faecal biomarkers
for colon cancer, Nice (2010–2012).
NHMRC Development Grant
• Blood based diagnostic assay for colorectal cancer,
Cosgrove/Nice/LaPointe/Gibbs/McMurrick/Ruszkiewicz/
Adams/Lockett (2011–2012).
16
Protein biomarker identification and quantitation by Multiple
Reaction Monitoring (MRM). In shotgun proteomics the total protein
mixture is digested and analysed by LC MS/MS to identify as many
proteins as possible (left panel). In MRM a known precursor mass is
selected and only the signature fragmentation (MS/MS) ions selected
for analysis (right panel). This approach reduces both signal complexity
and time for clinical samples to be analysed. Ang and Nice, Biomedical
Chromatography, 2011. 25: 82-99.
17
Annual Report 2011
Cancer
Dr John Price
Cancer Biology and Metastasis Laboratory
The major cause of death among cancer
patients is the spread of cancer from its
primary site of growth to distant organs
– a process called metastasis. Our primary
goal is to increase our understanding of
metastasis and to identify more effective
treatments for advanced cancers.
Research Fellows
Dr Michelle Kouspou
Dr Reece Lim
Research Assistant
Mrs Jessica Vieusseux
PhD Students
Mr Ryan Chai
Mr Benjamin Lang
Miss Chau Nguyen
Currently, there are no effective treatments that combat
the spread of cancer. To better understand this process,
we use cell lines and mouse models to identify genes that
associate positively or negatively with metastasis. We have
identified a group of genes that can predict which patients
will develop metastasised tumours. Many of these genes
are controlled by a molecule called Heat Shock Factor-1,
which we have shown is involved in cancer cell migration,
growth, survival and breast cancer metastasis. We are
currently screening for compounds that inhibit this molecule
in cancer cells to determine if this is an effective antimetastatic treatment approach.
NHMRC Project Grants
• Insulin-like growth factor binding protein-2 in cancer
cells, Werther/Russo/Price/Newgreen (2011–2013).
• Heat shock transcription factors in bone remodelling
and disease, Price/ Quinn/Benjamin (2010–2012).
The Cancer Council of Victoria Grant-in-Aid
• Role of Heat Shock Factor 1 in breast cancer metastasis,
Price/Hunter/Wilce (2009–2011).
Research Fellows
Dr Reidun Aesoey
Dr Preetika Balanathan
Dr Kara Britt
Dr Stuart Ellem
Dr Luc Furic
Dr Mitchell Lawrence
Dr Renea Taylor
Clinical Research
Fellows
Dr Antonio de Sousa
Dr Paul Manohar
Dr David Pook
Another concern is that cancers can become resistant
to drugs. To better understand this process, we have
generated cancer cells that are resistant to drugs called
HSP90 inhibitors. We hope to identify pathways and genes
that play a role in drug resistance, which may inform future
drug design programs.
Clinical and
Visiting Fellow
Dr Itsuhiro Takizawa
Research Assistants
NHMRC Project Grant
• Characterisation of the Grb7 protein involved in cellular
stress and cancer, Wilce/Price/Gorospe (2011–2013).
Enhancement of invasive cancer cell growth of human mammary
epithelial cells (MCF10A) when both H-Rasv12 oncogene and activated
Heat Shock Factor-1 (HSF1) are produced at the same time.
Ms Genevieve Dall
Mr Samuel Hawthorne
Ms Shelley Hedwards
Ms Hayriye Hussein
Dr Brindi Niranjan
Mrs Michelle Richards
Mrs Hong Wang
Bio-Resource
Co-ordinator
www.med.monash.edu.au/biochem/staff/price.html
Dr Melissa Papargiris
PhD Students
Cellular Signalling and Human Disease
Laboratory
Our goal is to understand how cell
communication networks (cellular signalling)
are altered in obesity, type 2 diabetes, immune
diseases and cancer.
Research Assistants
Our laboratory uses rodent, fruit fly and cell-based
models to study the role of protein tyrosine phosphatases
(PTPs) in tyrosine phosphorylation-dependent signalling
pathways implicated in normal biological processes and
in the development of human disease. A key interest
of our laboratory is delineating the roles of PTPs in the
control of body weight and glucose homeostasis and in
the development of obesity and type 2 diabetes. We are
interested in the regulation of insulin signalling in peripheral
tissues, leptin and insulin signalling in the brain, and how
inflammation contributes to the development of diabetes
and obesity.
PhD Students
We also study the control of T cell signalling and how
PTPs can contribute to the development of auto-immune
disorders such as type 1 diabetes, rheumatoid arthritis and
inflammatory bowel disease.
Research Fellows
Dr Stephanie Decherf
Dr Esteban Gurzov
Dr Troy Merry
Dr Benjamin Shields
Dr Florian Weide
Dr Mary Zhang
Ms Sock Hui Chew
Ms Katja Lowe
Ms Teresa Tiganis
Ms Bree Buszard
Mr Kim Loh
Professor Gail Risbridger
Deputy Dean (Special Projects)
Prostate and Breast Cancer Research Program
Professor Tony Tiganis
• Regulation of insulin sensitivity by reactive oxygen
species (2010-2012).
• Regulation of insulin signalling and glucose homeostasis
by protein tyosine phosphatases (2009-2011).
• Regulation of T cell receptor signalling by TCPTP
(2009-2011).
Awards and Achievements
Professor Tiganis
• Loh et al., Elevated hypothalamic TCPTP in obesity
contributes to cellular leptin resistance. Cell Metabolism,
2011. Nov 2; 14(5): 684-699.
• Wiede et al., T cell protein tyrosine phosphatase
attenuates T cell signalling to maintain tolerance in mice.
The Journal of Clinical Investigation, 2011. Dec 1; 121(12):
4758-4774.
Ms Shirin Hussain
Ms Roxanne Toivanen
Ms Sarah Wilkinson
We conduct basic and clinical research into the
three conditions that affect the prostate gland:
prostate cancer, benign prostate hyperplasia
and prostatitis. We study stem cells in prostate
and breast cancer and the role that estrogen
plays in the onset of prostate disease.
Prostate Cancer Foundation of Australia Project Grant
Close affiliations with universities, hospitals and other
institutes complement the group’s research. We collaborate
with researchers and clinicians in consortia, including the
Prostate Cancer BioResource, Victorian Prostate Cancer
Research Collaboration and Andrology Australia.
Awards and Achievements
NHMRC Fellowship Grant
Ms Toivanen
• Male reproductive health including prostate cancer,
Risbridger (2011-2015).
NMHRC Enabling Grant, Australian Prostate Cancer
• Collaboration (APCC) Bio-Resource (currently known as
the Commonwealth Bank Australian Prostate Cancer
BioResource in partnership with Andrology Australia),
Clements/Tilley/Sutherland/Risbridger (2010-2014).
NHMRC Project Grants
• Defining the role of Activin C in gonadal and adrenal
tumorigenesis, Risbridger (2011-2013).
• New paradigm for external genitalia development,
Risbridger/Hutson (2011-2013).
• Novel estrogen therapy for advanced prostate cancer,
Risbridger (2010-2011).
Health Research Council of New Zealand
• Role of Activin C in prostate disease, Elspeth/Nicholson/
Risbridger (2009-2012).
Dr de Sousa
• 2010/2011 Marshall Prize in Surgical Training,
Department of Surgery, Faculty of Medicine, Nursing and
Health Sciences, Monash University.
• Finalist, Novartis Junior scientist competition.
• Recipient of Women in Endocrinology Young
Investigator award.
• Finalist, US ENDO 2011 Presidential Poster Competition,
Boston, US.
Ms Wilkinson
• Deakin University award: best oral presentation at the
2011 ASMR Victorian Student Research Symposium.
• Third prize, MBio Graduate School 3 Minute Thesis
Competition final.
• Defining stromal-cancer cell interactions for xenografting
human prostate cancer, Risbridger/Taylor/Berman
(2010-2012).
• Characterising the beneficial effects of estrogen on the
prostate gland, Risbridger (2011).
ARC Grant
• Keeping stem cells on track: maintaining organ and
tissue homeostasis, Risbridger/Taylor (2009-2011).
Australian Cancer Research Foundation Equipment
and Infrastructure
• The establishment of the ACRF Centre for Cancer
Genomic Medicine, Williams/Hertzog/Watkins/Jenkins/
Risbridger/Gillespie/Simpson/Fuller (2011).
Prostate Cancer Foundation of Australia and Cancer
Australia (co-funded)
• Mechanisms of abiraterone resistance in prostate cancer,
Davis/Risbridger/Nelson/Taylor/Mainwaring (2010-2012).
Complex arrangement of prostatic stromal cells in experimental models
of prostate cancer. Image: Ms Hong Wang.
Prostate Cancer Foundation of Australia and Cancer
Australia Concept Grants
• The potential of serine protease inhibitors to inhibit
cancer promoting affects of cancer associated
fibroblasts in prostate cancer, Pike/Britt/Risbridger
(2011-2012).
• Identifying progenitor cells in prostate tumour stroma,
Garget/Risbridger (2010-2011).
www.med.monash.edu.au/anatomy/research/prostate-breast-cancer.html
We are also interested in defining the roles of PTPs in tumour
development, in particular, in breast and colon cancers.
NHMRC Principal Research Fellowship
• Professor Tiganis (2011-2015).
NHMRC Project Grants
• Regulation of hypothalamic insulin and leptin signaling by
TCPTP (2011-2014).
• Characterisation of TCPTP as a tumour suppressor
(2010-2012).
18
www.med.monash.edu.au/biochem/tiganis-lab.html
PTP1B and TCPTP attenuate signalling in obesity.
19
Cardiovascular
Disease
Cardiovascular disease
kills one Australian every
11 minutes*
>> What causes hypertension, heart failure,
atherosclerosis, stroke and kidney disease?
>> How is blood pressure regulated?
>> How can we better treat cardiovascular
diseases, or prevent them from occurring?
*Heart Foundation
www.heartfoundation.org.au/information-for-professionals/
data-and-statistics/Pages/default.aspx
Annual Report 2011
Cardiovascular Disease
Associate Professor Kate Denton
Associate Professor Roger Evans
Dr Michelle Kett
Cardiovascular and Renal Physiology
Our group studies how the kidney, heart
and vascular systems are regulated.
NHMRC Senior Research Fellowship
Cardiovascular disease remains the greatest health challenge
facing society today. It significantly decreases quality of life
for millions of Australians. As integrative physiologists, we
study the complex interactions of body systems as a whole.
We use sophisticated multi-disciplinary approaches to better
understand normal physiology and disease processes. We
visualise the cardiovascular system and study its function
at all levels, from interactions between specific molecules
to the integrated organism. We aim to reduce the burden
of cardiovascular disease by identifying the mechanisms
causing hypertension, heart failure and kidney disease.
NHMRC Project Grants
In 2011, we achieved the following:
• Salt and cardiovascular disease: Does acute salt
sensitivity convey greater cardiovascular risk?
(2008–2011)
• Discovered new targets for the treatment of pregnancy
-induced hypertension, the most common complication
of pregnancy that threatens the health and well-being
of mother and child;
• Case-control study of hypertension in a disadvantaged
rural community in India (2011–2013).
• Renal AT2R’s are a therapeutic target for the treatment
of hypertension in women (2010–2012).
• Kidney tissue hypoxia: a common pathway to renal
failure (2010–2012).
• ACE-2 and diabetic complications (2009–2011).
• Underlying mechanisms of cardiovascular disease
(2009–2011).
National Heart Foundation of Australia Fellowship
• Dr Michelle Kett (2008–2013).
• Identified renal factors that make the blood pressure
of certain individuals sensitive to high salt intake
and obesity;
National Heart Foundation of Australia (Grants-in-Aid)
• Demonstrated that there are sex-differences in adult
heart function in offspring with intrauterine growth
restriction – even in the absence of hypertension;
• Glomerular number deficit does not, on its own, explain
the programming of hypertension (2010–2011).
• Role of the renin-angiotensin system vasodepressor
pathways in pregnancy (2011–2012).
Dr Amany Abdelkader
Dr Lucinda Hilliard
Dr Reetu Singh
Research Assistants
Ms Lisa Donnet
Ms Rebecca Flower
Dr Oded Kleifeld
Research Officers
Dr Sanjaya Kuruppu
Dr David Steer
Dr Rui Zeng
Research Assistants
Ms Iresha Hanchapola
Ms Josie Lawrence
Ms Shane Reeve
PhD Students
Dr Megan Rees
Ms Fei Tieng
Ms Kunkun Zhang
Our results indicate that peptidases play important roles
in blood pressure regulation: they are shed from the cell
surface, inactivate vasodilator peptides and also generate
vasoconstrictor peptides from inactive precursors. Therefore,
by manipulating the expression, cell surface location and
activities of these enzymes, we can potentially control
cardiovascular function.
ARC Centre of Excellence
• Structural and Functional Microbial Genomics, Adler/
Coppel/Meeusen/Hertzog/Whisstock/Rossjohn/Smith
(2009–2013).
ARC Discovery Grant
• Structural and functional alteration of red blood cells by
Babesia parasites, Cooke/Smith/McElwain/Narla
(2010–2012).
Victoria’s Science Agenda Strategic Project Fund
• Victorian biomedical imaging capability, Smith/Kirk/
Connelly/Duchesne/Szoeke/Egan/Whitten/Kyrios
(2010–2013).
Awards and Achievements
Professor Smith
• Member, Federal Government (DISSR) Expert Working
Group: Promoting and Maintaining Good Health,
Infrastructure Road Map 2011.
• Member, BioImaging External Advisory Board, ESFRI
Roadmap for Research Infrastructures, Euro-Bioimaging
Project, 2011-.
• Member, Advisory Board, South-East Asian Observatory.
NHMRC Enabling Grant
• Imaging and therapeutic medical beamline for the
Australian Synchrotron, Smith/Lewis/Pearson/
Hausermann (2009–2012).
• Melanocortin regulation of reproduction, Clarke/Smith
(2009–2011).
NHMRC Program Grant
• Control of proteases in infectious, degenerative and
cardiovascular disease, Whisstock/Bird/Buckle/
Bottomley/Pike/Smith (2008–2012).
• Developed a mathematical model of oxygen transport
in the kidney;
Research Officers
Research Fellow
We are especially interested in the peptidases that line
the blood vessels. These enzymes can generate and break
down peptide hormones which are involved in the regulation
of blood pressure. Our long-term goal is to understand
which physiological and disease-causing factors control
the expression and cell surface location of these peptidases.
We work with the structural biology group and medicinal
chemists to design and characterise specific enzyme
inhibitors of potential therapeutic value. We use
proteomics-based technologies to study both the type and
levels of enzymes that are expressed on the surface of the
cells lining blood vessels.
Professor Ian Smith
Pro Vice-Chancellor (Research and
Research Infrastructure)
NHMRC Project Grant
• Identified components of the renin angiotensin system
that contribute to diabetes-induced kidney damage;
Dr Russell Brown
Dr Gabriela Eppel
Dr James Pearson
Dr Niwanthi Rajapakse
We aim to characterise and better understand
how peptide metabolising enzymes control
cardiovascular function.
• Associate Professor Denton (2008–2012).
• Demonstrated that there are sex-differences in the way
in which the renin-angiotensin system, a major regulator
of arterial pressure, regulates kidney function, which may
protect women from developing cardiovascular disease;
Research Fellows
Peptide Biology and Proteomics Laboratories
• Showed how kidney oxygen levels are altered in
response to changes in oxygen delivery and oxygen
consumption;
• Determined what causes the kidney to be starved of
oxygen despite restoration of blood flow after kidney
transplantation; and
Distribution of α-MSH in the arcuate nucleus and pituitary gland
by in situ hybridization and immunohistochemistry. (A): Neurons
express POMC mRNA in the sheep arcuate nucleus; (B): MSH staining
in the pars intermedia, PI; (C): MSH cells in the pars distalis, PD, are
distributed in scattered clusters. PN: pars nervosa. 3V: third ventricle.
www.med.monash.edu.au/biochem/research/projects/petptidebiol.html
www.med.monash.edu.au/biochem/facilities/proteomics/index.html
• Identified a candidate growth factor that may help repair
damaged kidneys.
The normal decrease in blood pressure seen during pregnancy requires
the presence of the angiotensin type 2 receptor (AT2R).
PhD Students
Mr Xiaochu Cai
Mr Mathew Jenkins
Mr Yugeesh Lankadeva
Ms Katrina Mirabito
Ms Melissa Tjongue
www.med.monash.edu.au/physiology/research/bloodpressure
Honours Students
Ms Yi Ching (Peggy) Chen
Mr Vatche Douzmanian
Ms Debra Fong
Mr Sarabjit Hansra
Ms Priyadharshani
Kalaignanasundaram
Mr George Konstantinidis
Ms Fiona Lewis
Ms Kristen Moore
Ms Jennifer Ngo
Ms Pei Chen (Connie) Ow
Ms Laura Wirth
22
23
Annual Report 2011
Cardiovascular Disease
Vascular Biology and
Immunopharmacology Group
Heart attacks and strokes occur when cardiac
or brain tissue is deprived of blood due to the
blockage of an artery. We aim to identify the
disease pathways within the blood vessel wall
that lead to blockages, as well as inflammatory
mechanisms that cause cell death. We are
interested in whether the immune system can
be regulated by drugs, vaccines or stem cells,
to prevent or minimise damage from heart
attacks and strokes.
We have shown that the Nox2 oxidase protein makes
excess oxygen radicals in cardiovascular diseases. By
comparing the development of artery lesions in fat-fed mice
with mice deficient in Nox2 oxidase, we discovered that
oxygen radicals released by this protein contribute to artery
hardening before heart attacks occur. This free-radical
production is markedly increased in brain arteries, which
may limit blood flow – even in healthy blood vessels.
Research Fellows
Dr Brad Broughton
Dr Klaudia Budzyn
Dr Sophocles Chrissobolis
Dr Stephanie de Dios
Dr Courtney Judkins
Dr Barbara Kemp-Harper
Dr Alyson Miller
Dr Stavros Selemidis
Research Assistants
Mr Henry Diep
Ms Elizabeth Guida
Mrs Elizabeth Hooker
Mr Suresh Kaushik
Ms Kate Maxwell
PhD Students
Ms Vanessa Brait
Ms Michelle Bullen
Mr Michael De Silva
Mr Craig Harrison
Ms Jacqueline Ku
Ms Sandy Lee
Mr Jeffrey Moore
Ms Jennifer Ravera
Ms Ravina Ravi
We have discovered evidence to suggest that males are
less able to recover from brain damage following stroke
than females. This is because more oxygen radicals are
released by Nox2 oxidase in males in brain-affected
tissues. Therefore, it is important to develop new drugs
that inhibit Nox2 oxidase for patients at risk of heart
attacks or stroke.
NHMRC Senior Research Fellowships
• Associate Professor Sobey (2010–2014).
• Dr Drummond (2011–2015).
Associate Professor Chris Sobey
Dr Grant Drummond
NHMRC Project Grants
• Does a novel estrogen receptor worsen stroke outcome?
Sobey/Broughton (2011–2013).
• Role of a Down syndrome-related protein in stroke
outcome, Sobey/Pritchard (2010–2014).
• Are novel nitric oxide mimetics protective in vascular
disease? Kemp-Harper/Drummond/Ritchie/Miller
(2010–2012).
• Aberrant oligosaccharide processing of Nox2-oxidase
as a mechanism of vascular oxidative stress in
atherosclerosis, Drummond/Sobey (2009–2011).
Lecturer
• Regulation of vascular tone by kynurenine,
Stocker/Sobey (2009–2011).
Dr Tracey Gaspari
High Blood Pressure Research Council of Australia
Research Fellowship
• Dr Chrissobolis (2011–2013).
Heart Foundation Grants-in-aid
• Aldosterone and the mineralocorticoid receptor
in cerebrovascular disease, Sobey/Chrissobolis
(2011–2012).
• Pharmacological inhibition of Ly6Chi monocyte entry into
the artery wall as a novel treatment for atherosclerosis,
Drummond/Sobey/Ricardo (2010–2011).
Dr Emma Jones
Research Fellow
Larkins and Heart
Foundation Fellow
Dr Antony Vinh
Research Assistant
Ms Iresha Welungoda
Integrative Cardiovascular
Pharmacology Group
Professor Robert Widdop
Head (Research), Department of Pharmacolgy
We are interested in novel treatments for
hypertension, atherosclerosis and stroke,
with an emphasis on drug targets associated
with the renin-angiotensin system.
Therefore, our research shows that angiotensin II regulation is
a highly complex process. We have also identified novel drug
targets for cardiovascular diseases which oppose the view
that angiotensin II evokes only excitatory effects.
Excessive amounts of the hormone angiotensin II can over
stimulate unique binding sites in the heart and blood vessels
called AT1 receptors, causing high blood pressure. The AT1
receptor can be blocked by molecules in the ‘sartan’ family,
which are used to treat hypertension, heart disease and
other cardiovascular complications. However, our research
suggests that stimulating other angiotensin-related sites may
counteract the negative effects of high angiotensin II levels.
Other sites include AT2 and Mas receptors, and enzymes
such as ACE2 and IRAP. Indeed, the parent hormone
angiotensin II is metabolized in the body to smaller fragments
which may then act as endogenous activators at lessconventional sites.
NHMRC Project Grants
• Central AT2 receptor stimulation improves stroke
(2011–2013).
• Renal angiotensin type 2 receptor is a therapeutic target
for the treatment of hypertension in women (2010–2012).
Heart Foundation Grants-in-Aid
• Targeting insulin regulated aminopeptidase/AT4 receptor
in the treatment of cardiovascular disease (2011–2012).
• Novel AT2 receptor-selective peptides (2010–2011).
PhD Students
Ms Sanja Bosnyak
Ms Damie Phua
Ms Sonja Tesanovic
Honours Students
Mr Tyrone Barnes
Mr Antony Sutherland
Cancer Council of Victoria Project Grant
• Novel pharmacological targets for suppression
of tumour angiogenesis, Selemidis/Williams/Drummond
(2010–2012).
NHMRC Career Development Award
• Dr Alyson Miller (2009–2012).
NHMRC CJ Martin Overseas Postdoctoral
Training Fellowships
• Dr Budzyn (2007–2011).
• Dr Chrissobolis (2005–2011).
NHMRC Peter Doherty Australian Postdoctoral
Training Fellowship
• Dr de Dios (2008–2011).
MSc Student
Mr Janahan Dharmarajah
Honours Students
Mr Chris Chan
Ms Quynh Dinh
Mr Ian Harrison
Ms Rushita Kalidindi
Ms Shalini Krishnan
Ms Kim Taylor
24
Cellular localisation of Nox isoforms through a cross section of
artery. A zoomed view of a cell shows the subcellular localisation of
each enzyme complex. From Drummond, G.R. et al., Nature Reviews
Drug Discovery, 2011. 10: 453-471.
www.med.monash.edu.au/pharmacology/research/vbig.html
Summary of the regulatory mechanisms controlling the synthesis, metabolism and cardiovascular actions of angiotensin II and its related family
of peptides.
www.med.monash.edu.au/pharmacology/research/intergrative-cardio-pharm.html
25
Developmental
Biology
Understanding how
organisms grow and
develop from a single cell
>> What genes control embryonic, stem
cell, cancer and organ development,
and tissue repair?
>> How does a mother’s diet in pregnancy
affect her child’s long-term health?
>> What are the causes and consequences
of premature birth?
>> How do steroid hormones increase the
survival of premature babies?
>> How can we develop stem-cell based
treatments for lung-related diseases?
>> How do sperm develop and function,
and what are the causes of male infertility
and testicular cancer?
>> How do inflammation and the immune
system contribute to eye diseases?
>> How do genes contribute to brain and
immune system changes in individuals
with Down syndrome?
Newborn mouse heart, showing cell membranes (green), cell proliferation (red),
nuclei (blue) and proliferating cardiomyocyte nuclei (pink). Image: Ms Kom Yin
and Mr Jonathan Bensley.
Annual Report 2011
Developmental Biology
Epithelial Regeneration Laboratory
Research Fellow
Dr Katja Horvay
Research Assistants
Ms Helen Lescesen
Ms Emma Murphy
PhD Students
Ms Lisa Kass
Ms Genevieve Kerr
Mr Rui Liang
Honours Student
Ms Sivan Elishav
Dr Helen Abud
Our research centres on understanding
how stem cells control cellular growth and
differentiation in the epithelial lining of the
intestine, and how disruptions in this process
cause intestinal disease.
NHMRC Project Grants
The intestinal epithelium or bowel lining is a regenerative
tissue that is constantly renewed throughout life via a small
population of stem cells. We are interested in defining the
mechanisms controlling intestinal stem cell differentiation
and how a balance between cell division and the production
of specialised, differentiated cell types is normally established
in the intestine. Intestinal diseases and abnormalities are
common clinical problems that can lead to the loss of
epithelial tissue in infants and adults. In contrast, colorectal
or bowel cancer can develop when there is an
overproduction of epithelial tissue. The molecular and
cellular processes that control growth in the intestine
are crucial yet poorly understood.
• The Impact of Wnt signalling on spermatogenesis
(2011–2013).
Our laboratory is studying how several signalling molecules
regulate intestinal stem cells, including Snai-1 and DNp73.
The expression and function of Snai-1 and DNp73
are also being studied in bowel cancer tumour models.
• Building an intestine: manipulating regeneration of the
epithelium (2011–2013).
We study fetal kidney development, the
impact of suboptimal kidney development on
fetal and adult health, and kidney regeneration
following disease.
NHMRC Development Grant
• Nephron endowment: are more nephrons necessarily
better? Bertram/Kett/Armitage/Caruana (2010–2011).
Ms Rebecca Douglas-Denton
In 2011 we: (1) studied the effects of gestational diabetes
on kidney development; (2) developed a new magnetic
resonance imaging method for visualising and quantifying
glomerular number and size in whole kidneys; (3) investigated
the relationship between body size and podocyte number in
humans; (4) studied the effects of specific genes and
feto-maternal environmental factors on urinary tract
development; and (5) investigated how risk factors for
chronic kidney disease impact on kidney microanatomy,
including glomerular number and size.
PhD Students
NHMRC Project Grants
• Functional studies on the role of DNp73 in stem cells
and cancer (2011–2013).
Research Fellows
Dr Georgina Caruana
Dr Luise Cullen-McEwen
Research Officer
Dr Reetu Singh
Research Assistant
The intestinal epithelium is a monolayer of cells that is constantly
renewed throughout life via a small population of stem cells. This image
shows a crypt from the small intestine where all nuclei are stained (blue)
and stem cells highlighted (green).
Ms Sarah Henry
Ms Stacey Hokke
Dr Victor Puelles
Mr Kenneth Walker
Mr Ryan Wood-Bradley
Honours Student
Ms Shughla Satari
Summer Student
www.med.monash.edu.au/anatomy/research/epithelial-regeneration/index.html
Developmental Origins of Obesity Related
Hypertension
PhD Students
Mr Benjamin Barzel
Ms Sarah Henry
Ms Stacey Hokke
Mr Ryan Wood-Bradley
Masters Student
Ms Aurora Elisaia
The prevalence of obesity and related diseases
are rising worldwide due to a combination
of adult risk factors. The environment
encountered in utero may also affect the
way that fetuses grow, making them more
susceptible to developing obesity and
hypertension in later life. We study the role of
the brain, sympathetic nervous system and
kidney in the development of obesity-related
hypertension in adulthood. We also examine
how being born to a diabetic mother or one
who consumed a diet high in fat or folic
acid in pregnancy affects fetal kidney
development and adult disease.
National Heart Foundation Grants-In-Aid
Monash Fellowship
• How might exposure to maternal fat rich diets during
development ‘programme’ the development obesity
related hypertension? (2007–2012)
• Hypoxia is the common pathway to renal disease, Evans/
Bertram/Schlaich/Gardiner/Smith/Phillips (2010–2012).
• New insights into the role of renal endothelial dysfunction
in the pathogenesis of glomerular injury and renal
fibrosis, Li/Bertram (2010–2012).
Research Assistants
Ms Anna Dick
Ms Kom Yin
PhD Students
Mr Jonathan Bensley
Ms Oksan Gezmish
Ms Vivian Nguyen
Mr Paul Lombardo
Ms Megan Sutherland
Ms Vladislava Zohdi
www.med.monash.edu.au/anatomy/research/devorigins-obesityrelatedhypertension.html
Associate Professor Mary Jane Black
We study how exposure to adverse factors
in early life (such as maternal malnutrition,
vitamin D deficiency and premature birth)
can increase disease risk in adulthood. We
study how these factors influence the growth
of the baby whilst in the mother’s womb and
then subsequently how they affect long-term
renal and cardiovascular health.
• Nephron endowment: Are more nephrons necessarily
better? (2010–2011)
Optical projection tomographic image of a kidney from a 14 day old
fetus of a diabetic mouse. This kidney is abnormal, with two ureters
(pink shaded) and ureteric trees (silver shaded) developing within the
one kidney.
Human kidney glomerulus, showing podocytes (green), endothelial
cells (red) and nuclei (blue). Image: Dr Victor Puelles.
Cardiovascular and Renal
Developmental Programming
• How does maternal diet during pregnancy programme
offspring obesity related hypertension?: A pivotal role for
the sympathetic nervous system (2011–2012).
• A neurogenic basis of obesity hypertension: Role
of adipokines and ghrelin in regulating sympathetic
vasomotor activity (2009–2011).
Heart Foundation
www.med.monash.edu.au/anatomy/research/kidneydevelopment.html
Dr James Armitage
• Ocular perfusion pressure: A modifiable risk factor
for glaucoma (2009–2011).
• Novel methods for promoting organ development and
growth, Ricardo/Bertram/Wallace (2010–2012).
• Human podocyte depletion, glomerular hypertrophy and
glomerulosclerosis, Bertram/Hoy (2010–2013).
Ms Georgina Taylor
NHMRC Project Grants
Professor John Bertram
Head, Department of Anatomy and
Developmental Biology
Kidney Development, Pathology
and Regeneration
Honours Student
Ms Danica Vojisavljevic
It is important to understand how these early life insults
affect heart and kidney growth, since the functional units
of these organs (the cardiomyocytes and nephrons,
respectively) are only formed during early development.
A reduced complement of these functional units at birth
is likely to adversely impact on cardiac and renal health.
NHMRC Grants
• Does maladaptive remodelling of the heart and
vasculature in response to preterm birth lead to long-term
cardiovascular risk? Black/Polglase (2011–2013).
• Why is the kidney vulnerable to preterm birth?
Black/Hoy (2011–2014).
Newborn mouse heart, showing cell membranes (green) cell proliferation
(red), nuclei (blue) and proliferating cardiomyocyte nuclei (pink).
Image: Ms Kim Yin and Mr Jonathan Bensley.
www.med.monash.edu.au/anatomy/research/cardio.html
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Annual Report 2011
Developmental Biology
Developmental and RNA Biology
Pulmonary Development and
Programming Group
Dr Peter Boag
We are interested in the role of gene regulation
in reproduction. Specifically, we study how
specific pathways and molecular machines
drive RNA metabolism and development.
Research Fellow
Dr Lloyd Low
PhD Students
Mr Gregory Davis
Ms Madhu Sharma
Masters Student
Ms Tasha Mendes
Our group studies how early life factors
such as the intra-uterine environment and
premature birth can affect the developing
lungs and increase the risk of childhood and
adult respiratory illnesses such as asthma and
chronic obstructive lung disease.
Recently, there has been a fundamental shift in the way
biologists think about the role of RNA. No longer is RNA
considered an intermediary between gene and protein
synthesis. Instead, it is now clear that RNA is an extremely
important point of complex regulation of gene, which
significantly affects cellular function.
Research Fellows
We use the non-pathogenic roundworm C. elegans as our
model system to discover conserved pathways that regulate
mRNA translation, which are relevant to mammals.
Dr Robert DeMatteo
Dr Takushi Hanita
Dr Foula Sozo
NHMRC Project Grant
Ms Natasha Blasch
Ms Judy Ng
Research Assistants
• Post-transcriptional gene regulation in RNA-granules
(2010–2012).
PhD Students
Dissected C. elegans gonad stained for DNA (blue) and two proteins
(red and green) involved in RNA regulation. Image: Ms Madhu
Sharma Sengupta.
Ms Anzari Atik
Ms Sheen Bouch
Ms Nadine Brew
Ms Noreen Ishak
Ms Megan O’Reilly
Honours Student
Ms Danica Vojisavljevic
www.med.monash.edu.au/biochem/staff/boag.html
Environmental factors that can persistently alter lung
structure and function include: the fetus receiving inadequate
nutrients via the placenta, maternal cardiovascular disease,
maternal smoking and alcohol consumption, and respiratory
infections during infancy. Preterm birth affects 10% of all
pregnancies and can also affect lung development as a result
of ventilator-induced lung injury and inhalation of high oxygen
levels. Therefore, we are studying how these environmental
factors alter lung development and increase the risk of
respiratory illness following preterm birth, and how they
can be prevented.
NHMRC Program Grant
We study specific steroid and growth factor
hormones in the developing human lung, which
are important in extremely premature babies.
Steroids and other endocrine hormones help to maintain
the normal function of bodily organs and tissue systems.
Their inappropriate action can lead to common adult human
diseases such as hypertension, heart failure and metabolic
syndromes.
Research Fellow
Dr Daniel Bird
Research Assistant
Ms Judy Ng
PhD Students
Ms Nisha Antony
Ms Kirstyn Carey
Ms Sasha Firsova
Mr Fredrik Olsson
Honours Students
Ms Tiffany Choo
Ms Teresa Le
Steroid hormones exert their effects through intracellular
steroid protein receptors and are members of the nuclear
receptor super-family of ligand-dependent gene regulators.
We are studying their signalling pathways in the developing
lung (underdeveloped in preterm babies), liver, immune
system (leukaemia) and brain (depression). We are also
assessing their potential use in stem-cell based treatments
for a range of lung-related diseases. The development of
lung-like cells would be a major advance for the treatment
of injured lungs both in preterm babies and in adults with
respiratory disorders. We are also investigating how these
hormones regulate genes expressed in the lung, liver, fat
and brain.
NHMRC Research Fellowship
• Senior Principal Research Fellow (2011–2015).
Associate Professor Timothy Cole
NHMRC Project Grant
• Does caffeine affect the development of the very
immature brain: Dose response relationship? (2010–2012)
Cerebral Palsy Foundation Grant
• Can erythropoietin treatment provide long-term
protection against inflammation-induced brain injury?
(2010–2012)
We are also interested in how the developing brain, heart,
blood vessels and kidney are affected by intra-uterine
conditions and premature birth. By understanding how
organs develop and are affected by early life factors, our
aim is to develop strategies that could prevent or treat
serious respiratory diseases and related disorders.
• Improved respiratory support and outcomes for very
preterm babies (2011–2015).
Steroid Endocrinology and Respiratory
Development Laboratory
Professor Richard Harding
Small conducting airway (bronchiole) from an adult mouse exposed
to a high level of oxygen for 7 days after birth. The bronchioles of
adult mice briefly exposed to high oxygen levels in infancy have
greater amounts of airway smooth muscle and fewer bronchiolaralveolar attachment points. These changes may help explain why
impaired lung function is common in children and adults born
prematurely. Image: Megan O'Reilly.
www.med.monash.edu.au/anatomy/research/pulmonary.html
NHMRC Program Grant
• Improved respiratory support and outcomes for very
preterm babies, Hooper/Davis/Doyle/Harding/Cole/Moss
(2011–2015).
Endothelial Cells and Kidney Regeneration
Dr Jinhua Li
We study the role of endothelial cells in
kidney injury and regeneration in different
disease settings.
We have generated an endothelial cell-labelled mouse line
to study how endothelial cells become fibroblasts, cells that
cause kidney scarring. We are also testing the efficacy of a
candidate new drug to treat kidney scarring.
Research Assistants
Ms Xinli Qu
Mr Jun Yao
Regulation of the lung surfactant protein D gene (Sftpd) by the Creb1
transcription factor in the developing mouse lung and skin. Sftpd
expression is nearly totally absent in Creb1-deficient (-/-) mice.
In another project, we are investigating how a novel and
potent fat molecule plays critical roles in kidney repair and
endothelial cell regeneration. Our research into TGF-β/Smad
signalling indicates that protein modification triggers the
development and progression of kidney disease, suggesting
its therapeutic potential in kidney, liver, lung and heart fibrosis.
NHMRC Project Grants
• Resolvin E1 is a novel anti-inflammatory and anti-fibrotic
lipid mediator for the treatment of chronic kidney disease
(2010-2012).
• New insights into the role of renal endothelial dysfunction
in the pathogenesis of glomerular injury and renal fibrosis
(2010-2012).
Normal (green) and damaged (red) kidney cells.
NHMRC Career Development Award
• (2010–2013)
www.med.monash.edu.au/anatomy/staff/fellows/jinhuali.html
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Annual Report 2011
Developmental Biology
Testis Growth and Germ Cell
Development Laboratory
We study how sperm develop normally from
pluripotent precursor cells during fetal and
juvenile life, what molecules are involved in this
process, and what factors reduce fertility and
cause testicular cancer in humans.
Research Fellows
Dr Catherine Itman
Dr Yoichi Miyamoto
Dr Guillaume Morin
Dr Wendy Winnall
Dr Julia Young
Research Assistants
Ms Elizabeth Richards
Ms Penny Whiley
Mr Chin Long Wong
PhD Students
Mr Arash Arjomand
Dr Badia Barakat (PhD
awarded August 2011)
Ms Genevieve Kerr
Mr Andrew Major
Ms Laura Tubino
Honours Students
Ms Hoey Koy
Ms Jessica van Gent
Ms Anmei Vuong
Visiting Scientist
Dr Shi-feng Li
We investigate how growth factors, including activin,
hedgehog and Wnt proteins, signal to drive development
of sperm precursors, and promote the growth of somatic
cells that form the testis. We discovered that the activin A
protein acts to creates a balance between the number of
spermatogonial cells and the size of their niche in the growing
testis. In this way, activin A controls events that establish the
potential for sperm production in adult life and thereby
determines adult fertility.
Professor Kate Loveland
The Ocular Immunomorphology Group
• Nuclear roles for importin alpha proteins, Loveland/
Miyamoto/Hecht/Yoneda (2008–2012).
We study the development of the eye, and
how inflammation and the immune system
contribute to eye diseases.
Awards and Achievements
Projects currently underway in our laboratory include:
ARC Discovery Project
Professor Kate Loveland
• Co-convenor of TGFβ Down Under 2011, Melbourne
Australia.
Monash Early Career Grant
• Are nanotubes a novel means of cell-cell communication
in the immune system? Chinnery/McMenamin (2011).
• The role of monocyte-derived cells in corneal
inflammation;
• The role of microglia in diabetic retinopathy;
• American Society for Andrology Council member,
2011–2014.
Research Fellows
Dr Catherine Itman
• Society for Reproductive Biology – University of
Newcastle Early Researcher Award semi-finalist.
PhD Students
With increasing rates of human infertility and testicular
cancer, there is worldwide concern that exposure of the
developing testis to endocrine disruptor chemicals in our
environment interferes with the events required for normal
sperm formation. Cross-talk between these key growth
factors and reproductive hormones is now an important
focus of our studies which will uncover how genetics and
environment influence male health. Our recent discoveries
have revealed that altered activin signalling can also govern
the pace of puberty onset, with precocious puberty an
increasing concern in human populations.
Professor Paul McMenamin
Dr Holly Chinnery
Dr Jelena Kezic
Mr Kevin Su Men Chang
Ms Xiangting Chen
Mr Yashar Razavi
Dr Nina Vagaga (Lions Eye
Institute)
Research Assistants
Dr Aaron Magno (LEI)
Ms Manpreet Sidhu
• The role of macrophages in age-related retinal
degeneration;
• How membrane nanotubes improve cell-cell
communication in the immune system;
• Eye evolution in marsupials to better understand
the structure and function of the eye; and
• Eye development and how macrophages (white
blood cells) remodel the retina and lens.
We also collaborate with research partners at the Lions Eye
Institute, in Perth; University of Western Australia; and The
Centre for Eye Research Australia, Melbourne.
NHMRC Project Grants
• Do resident immune cells cause retinal damage
in diabetes? (2010-2012)
• Role of Toll-like receptors in corneal inflammation
(2009-2011).
We also study the importin family of proteins that ferry other
proteins into the cell nucleus and thereby control cellular
maturation. We have recently discovered that importins also
work inside the nucleus to control gene expression, both in
normal cells under stress, and in sperm precursors.
A fundus picture of the retina in a mouse whose microglia express
Green Fluorescent Protein. The vessels are made visible by the
intravenous injection of a red fluorescent dye.
www.med.monash.edu.au/anatomy/research/ocular.html
NHMRC Senior Research Fellowship
• Professor Loveland (2009–2013).
NHMRC Project Grants
• The impact of Wnt signaling on spermatogenesis,
Loveland/Abud (2011–2013).
Sperm producing tubules of mouse testis, showing SPC1 (red), importin
alpha 2 (green) and chromatin (blue). Image: Andrew Major.
• Development of specific activin antagonists for
therapeutic applications, Harrison/Loveland (2011–2013).
• Activin in testis development and disease, Loveland/
Meachem/Hedger (2009–2011).
www.med.monash.edu.au/biochem/staff/loveland.html
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Annual Report 2011
Developmental Biology
Male Infertility and Germ Cell Biology
Laboratory
We study sperm development and function
and the causes of human male infertility.
Dr Kathleen DeBoer
Dr Duangporn Jamsai
Dr Adam Koppers
Approximately 1 in 20 Australian men are infertile and for the
majority of these individuals there is no specific diagnosis.
Sperm development is a fascinating process that requires
the co-ordinated activation of thousands of genes. It involves
stem cell renewal, meiosis, cell changes and complex posttranslational mechanisms, which regulate sperm function.
We use models of infertility and cell biology assays to define
key proteins and pathways for fertility. This research has
direct implications for the diagnosis of human infertility,
and the development of therapies and contraceptives.
Research Assistants
NHMRC Senior Research Fellow
Post-doctoral Fellows
Mr Brett Clark
Mr Francesco Marino
Ms Jo Merriner
Ms Anne O’Connor
Ms Stephanie Smith
PhD Student
Ms Jennifer Lo
Honours Students
Ms Rebecca D’Sylva
Ms Danielle Rhodes
• (2009–2013)
NHMRC Project Grants
• A new model of asthenospermia and a candidate gene
for multiple ciliopathies (2010–2012).
• The mechanism of spermatid differentiation – A link to
tumour suppression (2010–2012).
• The Australian Phenome Bank (2010–2011).
• Australian Centre for Vertebrate Mutation Detection
(2007–2011).
Victorian Government Department of Innovation and
Regional Development
• Partner Institutions: Monash University, Walter and Eliza
Hall Institute Institute of Medical Research, The University
of Melbourne (2007–2011).
Department of Education of Education, Science
and Technology
• Institutions: The Australian National University, Monash
University, Walter and Eliza Hall Institute of Medical
Research, Menzies Institute, Queensland Institute
of Medical Research, The University of Melbourne
Centenary Institute, Hanson Institute and Animal
Research Centre (2007–2011).
• Human sperm-oocyte interaction (2009–2011).
Dr Koppers
• 2011 International Society of Andrology Travel Award.
• Upgrade of the Clayton SP5 multiphoton microscope
to an upright configuration suited to small animal, organ
and whole-mount tissue imaging, Harper/Marcelle/
Lackmann/Bourne/Currie/McMenamin/Loveland/
O’Bryan/Verkade/Bowman/Burke/Warr (2011).
Research Fellow
Dr Alicia Corlett
PhD Students
Ms Katherine Martin
Mr Yong Yu
• Role of a Down syndrome-related protein in stroke
outcome, Sobey/Pritchard (2010–2014).
• The role of the Down syndrome-related gene DSCR1/
RCAN1 in learning and memory, Pritchard (2010–2011).
www.med.monash.edu.au/biochem/staff/pritchard-melanie.html
• 2011 Outstanding Trainee Award, American Society
of Andrology.
Organogenesis Laboratory
• A novel DNA damage repair protein as a regulator of
DNA double strand break repair and genome integrity,
O’Bryan/Jamsai/Ormandy/Handel (2011–2013).
Monash IVF Research Grant
• Studies on the genetic basis of male and idiopathic
infertility, and the trans-generational health of children
conceived through ART, O’Bryan/McLachlan/Jamsai
(2010–2011).
Deutsche Forschungsgemeinschaft International
Training Group Funding
www.med.monash.edu.au/anatomy/moiraobryan.html
Adult neurogenesis in the mouse brain. The dentate gyrus in the
hippocampus of an adult mouse brain is shown, with neurones (blue)
and newly formed neurones (green).
Fondation Jérôme Lejeune Project Grant
ARC Discovery Project
• Male Reproductive Health and Disease. German
participants: Meinhardt/Bergmann/Chakraborty/Fijak/
Linn/Middendorff/Steger/Weidner/ Baumgart-Vogt/
Paradowska/Schagdarsurengin. Australian participants:
Loveland/Allan/Hedger/McLachlan/O’Bryan/O’Donnell/
Stanton/Risbridger/Sinclair (2011).
We use genetically-modified mice to study the functions
of the DSCR1 and ITSN1. Both proteins regulate important
cellular signalling pathways. By studying mice that either
over-express the gene (as a model of Down syndrome) or
have the gene ‘turned off’, we are building a picture of how
DSCR1 and ITSN1 contribute to brain and immune changes
associated with Down syndrome.
NHMRC Project Grant
Awards and Achievements
Professor O’Bryan
• Appointed fellow of the Society for Reproductive Biology.
Dr Melanie Pritchard
We aim to determine how over-expression
of the genes DSCR1 and ITSN1 cause
abnormalities associated with Down syndrome.
We primarily focus on the brain, but also
study how elevated levels of DSCR1 lead to
abnormal immune function in Down syndrome.
In addition, we examine how DSCR1 protects
against brain damage during stroke.
The Australian Phenomics Network Infrastructure Grants
NHMRC Enabling Grants
• Cysteine-rich secretory protein regulation of ion channels
in male fertility and prostate cancer (2010–2012).
NHMRC Equipment Grant
Down Syndrome Research Laboratory
Professor Moira O’Bryan
Research Officer
Dr Kieran Short
Research Assistant
Ms Lynelle Jones
The mouse testis, showing microtubules (green), microtubuleprocessing enzyme (red) and nuclei (blue).
PhD Students
Ms Sally Ip
Ms Cecilia Naranjo-Golborne
Ms Tia Di Tommaso
Dr Ian Smyth
Our laboratory studies the developmental
cues important for the development of the
skin and kidney.
Human Frontier Science Project Grant
Using a number of animal models of human disease
such as Fraser syndrome and Harlequin ichthyosis, we
are investigating the biochemical processes which cause
these conditions. At a fundamental level we utilise an imaging
technique called Optical Projection Tomography to study the
mechanisms which drive branching of the developing kidney.
Together with our international and local colleagues, we
are modelling this process spatially and mathematically.
We also collaborate with the Wellcome Trust Sanger Institute
to identify novel mouse models of skin and kidney disease.
Awards and Achievements
• Modelling kidney development over space and time,
Little/McMahon/Smyth/Byrne (2011–2013).
Dr Ian Smyth
• Wellcome Trust Image award.
• Eureka Science Photography finalist.
Dr Kieran Short
• Wellcome Trust Image award.
NMRHC Project Grants
• Role of the 72 kDA 5-phosphatase in developmental
disease, Mitchell/Smyth/Dyson (2010–2012).
• The role of the transporter ABCA12 in lipid metabolism
and atheroclerosis, Smyth/Kile/Sviridov (2009–2011).
ARC Future Fellowship
• Using mouse genetics to understand skin development
and cell biology (2011–2014).
ARC Discovery Project Grant • A knockout approach to identifying genes involved in
epidermal development and homeostasis, Smyth/
Bradley/Watt/Jackson/Martin/Headon/Ramiro-RamirezSolis (2010–2012).
Imaging the developing mouse lung using Optical Projection Tomography.
www.med.monash.edu.au/anatomy/research/cutaneous.html
34
35
Drug Design
Understanding how hormones,
drugs, venoms and other
molecules act on cells
This information can be used to:
>> Design drugs that target specific receptors
>> Test drug action
>> Test the harmful effects of venoms
and toxins
Annual Report 2011
Drug Design
Professor Patrick Sexton
Professor Arthur Christopoulos
Professor Roger Summers
Professor Nigel Bunnett
Drug Discovery Biology Laboratory
We study how drugs, hormones and natural
chemicals act at the surface of human cells.
The optimum functioning of living cells, and consequently
the health of the entire organism, depends on how cells
respond to physical and chemical stimuli such as hormones
and neurotransmitters, which bind to specific cell surface
receptor proteins. G protein-coupled receptors (GPCRs)
are the largest superfamily of all receptors – about 2% of
the human genome and are the targets for nearly
40% of therapeutic drugs currently used.
We aim to understand how GPCRs are modulated, so
we can identify novel approaches for drug discovery.
We investigate GPCR structure and function, including
naturally occurring receptor variants; signaling via G
proteins and downstream messenger systems; interaction
of receptors with regulatory proteins; novel allosteric
GPCR interactions; biased signalling and modelling of
GPCR-ligand interactions.
We use relevant GPCR models to understand treatment
of metabolic, cardiovascular, inflammatory and central
nervous system disorders.
NHMRC Fellowships
• Australia Fellowship, Professor Bunnett (2011–2016).
• Principal Research Fellowship, Professor Sexton
(2009–2013).
Monash Venom Group
ARC Discovery Grants
We study the mode of action of venoms
and toxins from Australasian and overseas
reptiles, snakes and jellyfish.
• Understanding allosteric modulation and functional
selectivity at G protein-coupled receptors (GPCRs),
Christopoulos (2011–2013).
• Predictive modelling of ligand binding pockets in
G protein-coupled receptors, Sexton (2009–2011).
ARC Linkage Grant
• Relaxin: molecular mechanisms of cardioprotection,
Summers (2011–2013).
Research Fellow
Associate Professor Geoff
Isbister (Adjunct)
Research Officer
Monash Fellowship
Dr Nicki Konstantakopoulos
• Dr Canals (2010–2015).
PhD Students
NIH RO1 Grants
• Regulation of cellular responses to neuropeptides,
Bunnett (2011–2012).
• Protease signaling to the nervous system, Bunnett
(2011–2012).
VENI Fellowship
• Dr Lane (2010-2012).
Awards and Achievements
Professor Summers
• Honorary Professorial Research Fellow, Florey
Neuroscience Institutes (2009–2012).
Professor Wayne Hodgson
Head (Teaching and Research Training,
Department of Pharmacology (to November 2011)
Deputy Dean (Education) (from December 2011)
Ms Carmel Barber
Mr Janeyuth Chaisakul
Mr Andrew Hart
Ms Rachelle Kornhauser
Mr Usswin Santiphanpithaks
Mr Jure Skejic
Honours Students
Mr Steven Fernandez
Mr Kaijun Lin
Ns Nami Nagar
Mr Daryl Yang
We determine how venoms and toxins affect vital
physiological processes and how to counteract these
effects using antivenoms or novel therapeutic approaches.
We also identify venom components which may be used for
the development of new drugs to treat human diseases.
ARC Grants
• Molecular toxinology of Australia’s lesser
known venomous snakes (2010–2012).
• Evolutionary venomics: venom system
diversification in the animal kingdom (2007–2011).
The Hermon Slade Foundation
• Box jellyfish toxins: investigating novel protein
structure and function (2010–2012).
A comparison of the fangs from the Australian Coastal taipan, Oxyuranus
scutellatus (left) and the West African gaboon viper, Bitis rhinoceros (right).
Images: Venom Supplies, Tanunda.
• Cephalopod venom evolution (2008–2011).
www.med.monash.edu.au/pharmacology/research/venoms-toxins.html
• British Pharmacological Society Fellow (2005–).
• Senior Research Fellowship, Professor Christopoulos
(2008–2012).
• CJ Martin Fellowship, Dr Gregory (2011–2014).
• CJ Martin Fellowship, Dr van der Westhuizen
(2011–2014).
• CJ Martin Fellowship, Dr Sato (2010–2013).
• CJ Martin Fellowship, Dr Halls (2008–2012).
• CJ Martin Fellowship, Dr May (2008–2012).
• CDA Fellowship, Dr Hutchinson (2009–2012).
NHMRC Program Grant
• Understanding G protein-coupled receptors: accelerating
discovery from concept to clinic, Sexton/Christopoulos/
Summers (2009–2013).
NHMRC Project Grants
• Molecular characterisation of the glucagon-like peptide
1 receptor, Sexton/Simms/Canals (2011–2013).
• Bitopic ligands as a novel approach to G protein-coupled
receptor selectivity, Lane (2011–2013).
• Understanding new drug paradigms at M1 muscarinic
receptors, Canals (2011–2013).
Distinct transmembrane domain interactions govern selective
signalling of GPCRs. Mutation of the polar serine residues S155 or
S186 of the GLP-1 receptor to Ala leads to distinct effects on agonist
promoted signalling via cAMP accumulation, intracellular Ca2+
mobilisation or phosphorylation of ERK (left panels). Molecular models
of the transmembrane region of the receptor indicate that each residue
is likely to be involved in interactions in different subdomains of the
receptor, resulting in unique conformational changes upon mutation
(right panels). These data are helping us unravel how GPCRs translate
extracellular signals to intracellular responses.
• Understanding the pharmacoregulation of the
extracellular calcium sensing receptor, Christopoulos
(2009–2011).
www.pharm.monash.edu.au/research/mips/ddb/index.html
Personal Assistant
Ms Jessica Richardson
Senior Lecturer
Dr Richard Loiacono
Research Fellows
Dr Meritxell Canals
Dr Chris Choy
Dr Bronwyn Evans
Dr Sebastian Furness
Dr Karen Gregory
Dr Michelle Halls
Dr Caroline Hick
38
Dr Dana Hutchinson
Dr Martina Kocan
Dr Rob Lane
Dr Katie Leach
Dr Lauren May
Dr Masaaki Sato
Dr David Thal
Dr Celine Valant
Dr Emma van der
Westhuizen
Dr Denise Wootten
Research Assistant
Mr George Christopoulos
Technical Assistants
Mr Thomas Coudrat
Mr John Merlin
Dr Anne Stewart
Ms Christine Yeo
PhD Students
Ms Anna Davey
Ms Briana Davie
Mr Peter Keov
Ms Cassandra Koole
Ms Vindhya Nawaratne
Ms Kavita Pabreja
Mr Mohsin Sarwar
Ms Emilia Savage
Ms Su Suratman
Ms Georgina Thompson
Mr Adriel Wen
Masters Students
Ms Stephanie Catus
Ms Alla Abdul-Ridha
Honours Students
Mr Sam Dentry
Ms Linzi Lim
Mr Nathan Ryan
Mr Christopher Siwek
39
Immunology
Understanding how the body
defends itself from pathogens,
and how this defence sometimes
goes wrong and causes allergies,
asthma and autoimmune diseases
>> How do diet and microorganisms in the gut
contribute to autoimmune diseases and
cancer?
>> How can we develop anti-inflammatory drugs
for asthma and autoimmune diseases?
>> How can we harness the immune system to
treat cancer and autoimmune diseases?
The formation of germinal centres (white) in the spleen after immunisation.
Germinal centres are specialised lymphoid structures that produce high affinity
antibodies and generate B cell memory, which are the basis of vaccination.
Image: Louis Tsai.
Annual Report 2011
Immunology
Immunology and Biotechnology
Autoimmune diseases and asthma are
increasing in developed countries, and we
seek to understand and treat these conditions
based on new approaches, including the
manipulation of diet and composition of
gut microbes. We are also developing new
anti-inflammatory drugs that target new
molecules or cells involved in asthma
and autoimmune diseases.
Research Fellows
Dr Lauren Binge
Dr Nina Chevalier
Dr Laurence Macia
Dr Eliana Marino
Dr Remy Robert
Dr Alison Thorburn
Research Assistant
Mr Laurent Juglair
Honours Students
Ms Caroline Ang
Ms Josepha-Marie Cox
Ms Kate Rogers
Ms Megan Splittgerber
Diet affects the make up of gut flora. We found that a
metabolic product from the fermentation of fibre – short
chain fatty acids – has a marked anti-inflammatory effect
on inflammatory responses. It does this by binding to a
receptor expressed on immune cells called GPR43.
We have uncovered how GPR43 affects immune responses.
It interacts with chemoattractant receptors, macrophages
and dendritic cells and plays a role in epithelial cell integrity.
We have developed new monoclonal antibodies to treat
human inflammatory diseases. These are in various stages
of preclinical development. Promising new drugs under
development target the chemoattractant receptor molecules
CXCR7, CXCR3, CCR6, GPR43 and BAFF receptors. For
this work, we collaborate extensively throughout Monash,
including the Australian Regenerative Medicine Institute.
We have developed an extensive capability around antibody
engineering and hope to develop three additional antibodies
for human clinical trials.
NHMRC Australia Fellowship
• Professor Mackay (2010–2015).
Molecular Immunomodulation Laboratory
Professor Charles Mackay
We study the molecular mechanisms of
immune responses and how the immune
system can be harnessed to treat autoimmune
diseases and cancer.
NHMRC Project Grant
• Regulation of immune and inflammatory responses
by short chain fatty acids and GPR43 (2010–2013).
NHMRC Development Grant
• Development of anti-CXCR7 mAbs for the treatment
of fibrosis, Mackay/Sierro (2010–2012).
NHMRC Program Grant
• Cellular and molecular studies of the adaptive immune
response in health and disease, C Mackay/Sprent/
Goodnow/Basten/Cook/F Mackay/Vinuesa/Tangye/
Brink (2007–2011).
Research Assistant
Mr Yew Ann Leong
PhD Student
Mr Louis Tsai
International Honours
Students
Mr Anthony Chen
Ms Crystal Chen
Murine bone marrow derived neutrophils were plated onto glass
coverslips and stained for mouse beta-catenin (green), F-actin (red)
and the nucleus (blue).
www.med.monash.edu.au/immunology/research/imm-inflammation.html
Antibodies are used by the immune system to identify
and destroy pathogens. Generation of pathogen-specific
neutralising antibodies are the basis of most successful
vaccines. However, self-reactive antibodies (autoantibodies)
bind self-antigens, interfere with normal cellular functions
and cause autoimmune disease.
We and others have identified a new subset of immune
cells, called follicular helper T (Tfh) cells, which drive
antibody maturation and memory formation. Therefore,
Tfh cells are crucial for antibody-based vaccination and
play an important role in antibody-mediated autoimmune
diseases. We study how these cells differentiate and
function in genetically-modified mice, and hope to
design strategies to either promote antibody responses
or suppress autoantibody responses.
Dr Di Yu
NHMRC Career Development Award
• The biology of follicular helper T cells, Yu (2011–2014).
ARC Discovery Project Grant
• MicroRNAs and the control of T lymphocyte
differentiation, function and malignant transformation,
Yu (2011–2013).
Ramaciotti Establishment Grant
• A novel strategy of regulating follicular helper T cell
function to promote antibody responses (2011).
Larkins Fellowship (formerly known as Monash
Fellowship)
• Dr Yu (2011–2015).
For tumour cells to be rejected, several immune cells need
to be activated: T lymphocytes, dendritic cells and Natural
killer cells. Interleukin IL-21 (IL-21) is emerging as a key
molecule in this process, regulating specific cells. Preclinical
research indicates that IL-21 has antitumour effects, an
approach that is being tested in human clinical trials. Here,
we study genetically-modified mice that have IL-21 and IL-21
receptor replaced with human IL-21 and its receptor. We
hope to develop new approaches to boost anti-tumour
immunity through the IL-21 pathway for clinical application
NHMRC Project Grants
• Cytokine structure and mechanisms of a superagonist
antibody, Yu/Beddoe (2011–2013).
• Specialised subsets of T follicular helper cells in the
control of infection and immune pathology, Vinuesa/
Yu/Liston (2011–2013).
The formation of germinal centres (white) in the spleen after
immunisation. Germinal centres are specialised lymphoid structures that
produce high affinity antibodies and generate B cell memory, which are
the basis of vaccination. Image: Louis Tsai.
www.med.monash.edu.au/immunology/research/molecular-immunomodulation.html
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Immunology and
Stem Cells
How can stem cells
>> Form medically relevant cells?
>> Be delivered to sites of injury,
inflammation and disease?
>> Regenerate damaged tissue?
>> Be used as a model for
Huntington’s disease?
>> Avoid immune rejection?
What role does the thymus
play in automimmunity,
immunodeficiency,
and tissue and stem
cell rejection?
Kidney cells in culture.
Annual Report 2011
Immunology and Stem Cells
Neuroimmunology
Research Fellows
Dr Sara Litwak
Dr Leon Moussa
Dr Chris Siatskas
Dr Bi Song
Dr Guizhi Sun
Research Officers
Ms Noami Canpanale
Ms Daniella Herszfeld
Research Assistants
Mr Ashley Emerson-Webber
Ms Aude Sylvan
Ms Nadege Veron
Ms Kerry Webber
PhD Students
Ms Sally Cain
Ms Courtney McDonald
Ms Natalie Payne
Dr Martin Short, MBBS, FRACP
Professor Claude Bernard
Multiple sclerosis (MS) is a debilitating disease
that affects the central nervous system (CNS).
Although the precise triggers remain elusive,
the ultimate end point of the disease is the
destruction of nerve axons and myelin, two key
cellular components of the CNS involved in the
conduction of nerve impulses. At present, there
is no cure for this severe neurodegenerative
condition. Therefore, there is an urgent need
to understand the causes of this and other
central nervous system disorders, so that more
effective treatments can be developed.
California Institute for Regenerative Medicine and
Victorian Government
As an important first step, we have developed a novel
approach to detect harmful cerebrospinal fluid molecules and
brain proteins from patients with multiple sclerosis. Using
this assay, we have identified novel reactive CSF proteins
in the brain and tested their effects in experimental models
of chronic-active MS. A variety of new therapeutics could
possibly emerge from these studies.
Awards and Achievements
We have also manipulated adult skin cells from MS patients
and converted them into stem cells, using a technique
called induced-pluripotent stem cells. We showed that these
MS stem cells could differentiate into neurons and myelinproducing cells. By reprogramming cells from patients with
MS into nerve cells, we may increase our understanding of
this debilitating disease.
Immune Regeneration Laboratory
Associate Professor Ann Chidgey
Deputy Laboratory Head
• Engineering immune tolerance by stem cell-derived
thymic regeneration (2010–2012).
The Eva and Les Erdi AUSiMED Fellowship in
Neurological Diseases
The Immune Regeneration Laboratory
studies the structure, development and
function of the thymus under normal and
pathological conditions, including age- and
drug-induced degeneration. We aim to use
this knowledge to overcome clinical conditions
such as autoimmunity, immunodeficiency and
transplant rejection, including rejection of stem
cell therapies.
• Generation of induced pluripotent stem cell lines
from multiple sclerosis patients (2009–2013).
The Cure MS Fellowship in Neurological Diseases
• Cell therapy for neurodegenerative diseases by
progenitor cells derived from induced pluripotent
stem cells (2010–2012).
Professor Bernard
• Guest Professor, BaYi Brain Hospital, Beijing, China.
The thymus is the site of T cell production, and plays a vital
role in educating the immune system to distinguish between
‘self’ tissue and foreign invaders. However, the thymus
undergoes profound age-related atrophy, linked to the rise of
sex steroids in puberty, as well as chemotherapy, radiation,
HIV infection and environmental factors.
• Guest Professor, Kunming Medical University,
Beijing, China.
• Keynote speaker at the 2011 Life Science Symposium,
Kunming, China.
• Keynote speaker, 2011 China-Australia Symposium
on Stem Cell Research, Beijing General Hospital,
Beijing, China.
• Invited speaker, Grantee Meeting of the California
Institute of Regenerative Medicine, San Francisco, US.
NHMRC Program Grant
• Invited speaker, Australasian Autoimmunity Workshop,
Brisbane, Australia.
• Innovative stem-cell based strategies to establish
immune tolerance (2007–2011).
• Invited speaker, California Institute of Regenerative
Medicine/Australia Workshop, Melbourne.
Professional Officer
Mr Mark Malin
Personal Research
Assistant/Senior
Research Officer
Ms Samantha Harris
Personal Assistant/
Technical Assistant
ARC Discovery Grants
Ms Luciana Thompson
• Nerve regeneration using light responsive hydrogels and
stem cells (2010–2012).
Research Fellows
Dr Tracy Heng
Dr Natalie Seach
• Molecular characterisation of stem cell differentiation and
oocyte maturation using synchrotron infared
spectroscopy and atomic force microscopy/Raman
imaging (2008–2012).
ARC Linkage Grant
The Baker Foundation
AussiMed
• Stem cell therapies for neurological diseases
(2009–2013).
Biogen Idec Clinical Fellowship
• The fate of bone marrow derived cells following acute
inflammation of the central nervous system (2009–2011).
Californian Institute for Regenerative Medicine/
Victorian Government Department of Innovation,
Industry and Regional Development
• Thymus based tolerance to stem cell therapies
(2010–2013).
• Neural stem cells as a developmental candidate to treat
Alzheimer’s disease (2009–2012).
CSIRO-OCE Grant
• Combinatorial assembly of bioactive peptides to generate
selective biofunctional materials (2011–2013).
Neo Stem Cell (Hong Kong) Contract Research
Funding
• Research and development of neonatal stem cells (2011).
Taif University, Kingdom of Saudi Arabia Collaborative
Research Program
• Training TAIF scientists in stem cell research (2011).
Awards and Achievements
• Stem Cell Awareness Day public seminars, Federation
Square, Melbourne.
NHMRC Overseas-based Biomedical Fellowship
• (2011–2014)
NHMRC Program Grant
Ms Maree Hammett
Ms Lisa Spyroglou
• Innovative stem cell-based strategies to establish
immune tolerance and tissue repair (2007–2011).
Technical Officers
ARC Linkage Grant
PhD Students
• Application of direct protein transduction of stem cell
factors to reprogram mouse and human somatic cells
into pluripotent stem cells (2009–2011).
Mr Marco Barsanti
Ms Adrienne Calder
Ms Danika Khong
Ms Louisa Layton
Ms Joanna Lim
Ms Jessica Morison
Mr Anthony Park
Ms Chew-Li Soh
Ms Kahlia Wong
• The use of neural stem cells as a therapeutic tool
in neurological disorders (2007–2011).
In 2011, we studied the following research projects:
pathways involved in thymic and bone marrow ageing and
sex-steroid withdrawal-mediated regeneration; identification
and analysis of a putative adult thymic stromal progenitor cell;
differentiation of human embryonic stem cells to form thymic
stromal cells; isolation of mesenchymal stem cells (MSC)
from clinically viable sources; the application of isolated MSC
to treat asthma; and development of a clinically relevant
approach to improve the success of transplantation with
foreign cells and tissues.
Research Assistants
Ms Jade Barbuto
Ms Jade Homann
• Proteomic analysis of central nervous system
inflammation in multiple sclerosis (2010–2012).
Professor Richard Boyd
Director, Monash Immunology
and Stem Cell Laboratories
Australian Stem Cell Centre – Adult Stem Cell
Collaborative Stream (4)
• Adult thymic stem cells (2010–2011).
Australian Stem Cell Centre – Collaborative Stream (3)
• Characterisation of respiratory and thymic epithelium
derived from the in vitro differentiation of pluripotent stem
cells (2009–2011).
Distribution of Pax9 (green) in the thymus of an embryonic mouse at day
14 of gestation. Pax9 is a protein that activates genes involved in the
formation of the thymus. Image: Mr Marco Barsanti.
Honours Students
Adult skin cells taken from an MS patient, which have been converted
into stem cells, can become myelin-producing cells. These cells have on
their surfaces two common CNS myelin proteins: CNPase (green) and
myelin basic protein (red). The stem cell nucleus is stained light blue.
Ms Michelle Burns
Mr Michael Hun
www.med.monash.edu.au/miscl/research/immune-regeneration.html
www.med.monash.edu.au/miscl/research/neuroimmunology.html
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Annual Report 2011
Immunology and Stem Cells
Embryonic Stem Cell
Differentiation Laboratory
Professor Andrew Elefanty
Professor Ed Stanley
We study the directed differentiation of human
embryonic stem cells (hESCs) into medically
relevant human cells, including blood cells
(blood disorders), blood vessel cells (cancer
and hypertension), respiratory epithelium (lung
diseases) and pancreatic beta cells (type 1
diabetes).
ARC Special Research Initiative in Stem Cells (Stem
Cells Australia)
To assist us, we have generated geneticallymodified hESCs that express green or red
fluorescent proteins when they form cell types
of interest. We then isolate these fluorescent
cells and study their function.
• Methods for detection and elimination of residual human
embryonic stem cells in a differentiated cell product
(2009–2012).
Cardiac Stem Cell Laboratory
We aim to isolate and expand cardiac cells
derived from human embryonic stem cells, then
simulate heart disease in the laboratory and
improve our understanding of this disorder.
• Program 2: Directed differentiation of pluripotent stem
cells, Hilton/Elefanty/Stanley/ Nielsen/ Haylock/Nilsson/
Little (2011–2018).
CIRM-Victorian Government Early Translational
Research Award
Research Assistants
Ms Deevina Arasaratnam
Ms Kathy Koutsis
Mr Rhys Skelton
• Stem cell derived cardiomyocytes: tools for investigating
cardiac disease, Elliott/Kaye/Pouton/Haynes
(2009–2011).
• Professor Elefanty (2011–2015).
Ms Lisa Azzola
Ms Freya Bruveris
Ms Sonia Holland
Mr Roy Lee
Ms Robyn Mayberry
Ms Koula Sourris
NHMRC Project Grant
• Characterisation of human embryonic stem cell
differentiation to haematopoietic progenitors and stem
cells, Elefanty/Stanley/Nilsson/Haylock (2011–2013).
Human cardiomyocytes derived from embryonic stem cells. Cells
express green fluorescent protein (green), the transcriptional regulator
NKX2-5 and have a functional contractile apparatus (blue).
Qatar National Research Fund Project Grant
• Stanley/Tabrizi/Elliott/Elefanty/Costa (2010–2012).
NHMRC/JDF Special Program Grant in Type 1 Diabetes
• Derivation of pancreatic beta cells from embryonic stem
cells (2008–2012).
www.med.monash.edu.au/miscl/staff/david-elliott.html
ARC Discovery Grant
• Developing the basis for a quality control platform for
human pluripotent stem cells and their differentiated
derivatives, McNaughton/Stanley/Elefanty/Tobin
(2011–2013).
Panel of images showing differentiated hESC lines carrying lineage
specific fluorescent markers. The indicated genes mark differentiating
mesoderm (MIXL1), blood (ErythRED and RUNX1c), heart (NKX2.5),
pancreas (INSULIN), lung (NKX2.1) and nerve (NKX2.1).
Kidney Stem Cell and Regeneration Laboratory
www.med.monash.edu.au/miscl/research/embryonic-stem-cell.html
PhD Students
Ms Julie Cao
Ms Jennifer Durnall
Mr Rob Jenny
Ms Jacqueline Schiesser
Ms Chew-Li Soh
Mr Michael Wong
Ms Cissy Yu
• Isolation, expansion and characterisation of human
cardiac progenitor cells (2010–2012).
Australian Stem Cell Centre
Module 8: Pluripotent Stem Cell Stream
• Professor Stanley (2009–2013).
Research Assistants
NHMRC New Investigator Award
• The role of micro-RNAs in human cardiac specification,
White/Elliott (2011–2013).
NHMRC Research Fellowship Grants
Dr Magdaline Costa
Dr Antonietta Giudice
Ms Tanya Hatzistavrou
Dr Claire Hirst
Dr Andrew Holland
Dr Vanta Jokubaitis
Dr Sue Mei Lim
Dr Suzanne Micallef
Ms Elizabeth Ng
Dr Katerina Vlahos
We have generated a genetically-modified human embryonic
stem cell line that expresses green fluorescent protein in
heart muscle cells. Using this line, we have isolated earlyprecursor heart cells as well as more mature cardiomyocytes.
These cells allow us to study how heart cells behave and
cardiac diseases develop.
NHMRC Project Grant
We also collaborate with Dr David Elliott, who generates
heart muscle cells, and with Professor Richard Boyd, who
studies how hESCs can differentiate into thymic epithelium.
Research Fellows
Dr David Elliott
We aim to develop new stem cell-based
therapies that may offer alternatives for patients
with end-stage kidney disease undergoing kidney
transplantation and long-term dialysis.
NHMRC Development Grant
We are working on the following projects:
• Postnatal therapy for organ growth and repair
(2011–2013).
Generation of stem cells from patients with
kidney disease
Research Fellow
Dr Bi Song
Research Assistant
Ms Emerald Surrao
Mr Junli Zhuang
PhD Students
Ms Maliha Alikhan
Mr Adrian D'Arcy
Ms Christina Jones
Mr Timothy Williams
Ms Andrea Wise
Associate Professor Sharon Ricardo
We recently published the first report showing that stem
cells, called iPS cells, can be generated from human
kidneys. In the future, these patient-specific iPS cell lines
could potentially be used for drug testing and personalised
medicine, where treatment decisions are based according
to an individual patient’s disease profile. These stem
cells will also help us to better understand how kidney
disorders develop.
• Novel methods for promoting organ development
and growth (2010–2012).
NHMRC Project Grant
Awards and Achievements
Associate Professor Ricardo
• Amgen Basic Science Award, Australia and New Zealand
Society of Nephrology 2011.
A novel therapy for babies with kidney defects
There is growing evidence that genes involved in kidney
development also play a role in kidney regeneration,
‘switching on’ kidney repair following injury. We are testing
a protein for clinical trials that can promote kidney growth
and maturation. If successful, this protein could potentially
treat unborn babies with kidney defects when currently
there is no cure. We also hope to develop strategies that
promote kidney ‘self-repair’ and study blood-derived
immune cells, which play an important role in this process.
Kidney cells in culture.
www.med.monash.edu.au/miscl/research/renal-regeneration.html
48
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Infectious
Diseases
Understanding how
microorganisms cause
human or animal diseases
>> How do parasites, bacteria, viruses and fungi
cause diseases?
>> How do immune cells respond to infection?
>> How can we produce better drugs or
vaccines against infectious organisms?
>> How can we better treat asthma and other
respiratory diseases?
Malaria parasites bursting out of a human red blood cell.
Image: Professor Brian Cooke.
Annual Report 2011
Infectious Diseases
Biology of Granzymes and
Granzyme Inhibitors
We are interested in the killing mechanism
of cytotoxic lymphocytes, immune cells that
eradicate virus-infected or cancer cells from
the body.
Professor Phillip Bird
Acting Head of School
NHMRC Project Grant
• The impact of granzyme B on cytotoxic T cell migration
through tissue (2011–2013).
To kill abnormal cells, cytotoxic lymphocytes release two
key factors: a pore-forming protein called perforin and a
protease called granzyme B. Perforin mediates entry of
granzyme B into the interior of the target cell, causing death.
Research Fellows
Dr Dion Kaiserman
Dr Alexandra Rizzitelli
Research Assistants
Ms Cathy Bird
Ms Corinne Hitchen
Ms Jennii Luu
PhD Students
Also, these immune cells contain a granzyme B inhibitor,
PI-9, which protects them from being killed by granzyme B.
Some cancer cells overproduce PI-9, which may be a way to
evade the immune system, ensuring their survival. Currently,
we are studying the distribution and function of PI-9 within
cytotoxic cells in mice lacking this key protein.
Honours Student
www.med.monash.edu.au/biochem/staff/bird.html
Dr Lakshmi Wijeyewickrema
Research Assistant
Mrs Usha Koul
PhD Students
Ms Nicole Drentin
Ms Renee Duncan
Ms Rebecca Fitzpatrick
Mr Tang Yongqing
• Intracellular survival of Burkholderia pseudomallei and
the evasion of autophagy (2009–2011).
• Molecular and genetic basis of colistin resistance
in Acinetobacter baumannii (2009–2011).
• The vaccine potential of live, attenuated
leptospiral mutants;
ARC Centre of Excellence in Structural and Functional
Microbial Genomics
• The genetic and structural roles of cell surface molecules
of the pathogen Pasteurella multocida, which causes
numerous livestock infections, and their role in disease;
Australian Poultry CRC
• Professor Adler – Director (2005–2013).
• Rapid multiplex PCR assay for differentiating Pasteurella
multocida serovars (2011–2013).
• How LPS loss in Acinetobacter baumannii affects the
host immune system;
Research Fellows
Human cytotoxic lymphocytes migrating through extracellular matrix
(Matrigel) produce granzyme B.
Dr Elizabeth Allwood
Dr Thanatchaporn Bartpho
Dr Xenia Gatsos
Dr Marina Harper
Dr Rebekah Henry
Dr Renee Marcsisin
Dr Gerald Murray
Research Assistants
Ms Deanna Deveson
Ms Marietta John
Ms Kate Rainczuk
Research Fellow
In 2011, we investigated the following:
• Analysis and regulation of leptospiral virulence factors
(2009–2012).
• The mechanisms by which the multi-drug resistant,
hospital acquired pathogen Acinetobacter baumannii
develops resistance to colistin, a ‘last resort’ antibiotic;
Ms Aimee Parker
Protease Laboratory
NHMRC Project Grants
• How virulence genes of Pasteurella multocida
are regulated;
NHMRC Program Grant
• Control of proteases in infectious, degenerative and
cardiovascular disease (2008–2012).
We study how bacteria cause human and
animal diseases, and how the body’s immune
system responds to infection.
• The role of lipopolysaccharide (LPS) and other surface
components of Leptospira in leptospirosis infection of
animals and humans;
How granzyme B is released from cytotoxic lymphocytes
and enters target cells is unclear. However, we have identified
regions of granzyme B that are required for cell entry, and
have shown that its role extends beyond initiating cell death
in compromised cells. Our recent results indicate that the
enzyme allows cytotoxic lymphocytes to migrate through
tissue, and control blood clotting.
Mr Jamshaid Ahmad
Ms Susan Berkowitz
(with James Whisstock)
Mr Michael d’Angelo
Ms Aminah Giousoh
(with James Whisstock)
Mr Matthew Mangan
Mr Anthony Matthews
Ms Monica Prakash
Ms Sarah Stewart
Ms Sonia Teoh
Ms Evelyn Yip
(with Steve Bottomley)
Dr John Boyce
Professor Ben Adler
Bacterial Pathogenesis and Immunity
Professor Robert Pike
Head, Department of Biochemistry
and Molecular Biology
We study how proteases from bacteria and the
human immune system are involved in disease
processes. One major focus is the complement
system of immunity, which is the first line of
defence against pathogens. We also conduct
research on periodontal (gum) disease, which
is a major cause of tooth loss worldwide and
is also associated with other diseases.
ARC Linkage Grant
The complement system is vital to our immune system,
but unregulated complement activation has been linked to
many diseases, including cardiovascular and degenerative
diseases. We have shown how proteases that initiate
complement activation interact with their targets and
regulators. This information will help us design molecules
that inhibit key processes and combat disease.
• The potential of serine protease inhibitors to inhibit
cancer promoting effects of cancer associated
fibroblasts in prostate cancer, Pike/Britt/Risbridger
(2011–2012).
• Characterisation of plant cysteine proteases with
therapeutic potential, Pike/Whisstock/Song/Mynott
(2011–2014).
Oral Health Cooperative Research Centre
• Antagonists of host receptors and gingipains to prevent
progression of periodontal disease (2011–2013).
Prostate Cancer Foundation of Australia
The oral bacterium Porphyromonas gingivalis is a major
causative agent of periodontal disease. It makes proteases
that regulate many of the pathogenic activities of the
bacterium. We have shown how these enzymes interact
with the immune system to cause gum disease. We aim
to block key disease-causing molecules with candidate
inhibitors.
• How Burkholderia pseudomallei, which causes the
tropical disease melioidosis, interacts with and evades
defence mechanisms inside host cells; and
• Potential vaccine candidates for footrot, a serious
infection affecting sheep.
Shadowed electron microscope image of bacterial cell of pathogenic
Leptospira. Image: Annabella Chang.
www.med.monash.edu.au/microbiology/staff/boyce.html
www.microbialgenomics.net
Technical Officers
Mr Mark Edmunds
Ms Vicki Vallance
PhD Students
Ms Priyangi Alwis
Ms Sadia Deen
Ms Deanna Deveson
Ms Amy King
Ms Jennifer Moffatt
Ms Puthayalai Treerat
Mr Timothy Witchell
Ms Kunkun Zhang
Honours Students
Ms Hedieh Aklaghi
Mr Tim Fitzsimons
Ms Cara Nethercott
Undergraduate
Research Students
Ms Bethany Crane
Ms Sanvir Maharaj
Mr Luke Southey
Mr Stephen Watts
Academic Visitor
Dr Isabelle da Piedade
NHMRC Program Grant
• Control of proteases in infectious, degenerative and
cardiovascular disease, Whisstock/Bird/Bottomley/
Buckle/Pike/Smith (2008–2012).
Crystal structures of the catalytic and adhesin domains of a gingipain
(upper panel), together with the domain structure of the enzyme
(lower panel).
www.med.monash.edu.au/biochem/staff/pike.html
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53
Annual Report 2011
Infectious Diseases
Molecular Parasitology
Research Fellows
Dr Svenja Günther
Dr Nicholas Proellocks
Research Assistants
Ms Donna Buckingham
Mr Charles Ma
PhD Students
Ms Rimi Chakrabarti
Ms Sejal Gohil
Ms Ghizal Siddiqui
Undergraduate Student
(MIC3990)
Mr Kit Kennedy
Autophagy Laboratory
Professor Brian Cooke
Our group studies how parasites of red blood
cells (particularly malaria and babesia) cause
disease and death in humans and animals, with
the aim to develop new drugs or vaccines.
ARC Discovery Project Grant
Malaria is central to our research activities because it
affects over half of the world’s population, and still kills
about 1 million people each year. We also study babesia
parasites as these cause a malaria-like disease in cattle,
which results in huge economic losses to the beef and
dairy industries worldwide.
• Malaria and red blood cells (2008–2012).
• Structural and functional alteration of red blood cells by
Babesia parasites (2010–2012).
NIH Program Grant
Research Fellows
Eukaryotic cells degrade unwanted parts
of their internal structure by the process
of autophagy (“self eating”).
ARC Project Grant
In yeast, autophagy acts to remove unwanted or damaged
components of these cells and this helps them adapt to
starvation or other stresses.
• Design and fabrication of molecular machines: the
nanomachines of the future, Lithgow/Rossjohn/Devenish/
Martin/Strugnell (2011-2014).
Dr Lan Gong
Dr Dalibor Mijaljica
In 2011, we worked on the following projects:
Visiting Scientist
Removal of organelles by autophagy
Dr Xuelei Li
Autophagy in bacterial infection of mammalian cells
NHMRC Senior Research Fellowship
PhD Students
We are studying how the bacterium Burkholderia
pseudomallei can successfully survive in infected cells
without being destroyed by autophagy.
• Function of parasite proteins in malaria infection
(2009–2013).
Research Assistant
Malaria parasites bursting out of a human red blood cell.
Ms Tanya D’Cruze
Mr Alexander May
NHMRC Project Grants
Masters Student
• Exported malaria kinases and red blood cell
remodeling (2010–2012).
Honours Student
Ms Shu-chin (Alicia) Lai
Ms Alexandra Dimitropoulos
• SBP1 and altered structure and function of
malaria-infected red blood cells (2010–2012).
• Autophagy and the nucleus (2009-2011).
ARC Super Science Fellowship
In mammalian cells defects in autophagy can be linked
to pathological conditions, including: microbial and viral
infections, neurodegenerative and muscle tissue diseases,
and some forms of cancer.
Our group has shown that these parasites make red blood
cells stiff and sticky, which allows them to lodge in vital
organs such as the brain. We identify proteins that cause
these changes in red blood cells, so that new prevention
and treatment strategies can be developed. Our work is
recognised and supported both nationally and internationally.
Dr Xiao-Hong Liu
Professor Rod Devenish
We are trying to better understand how the nucleus is
degraded when yeast cells are starved of nutrients.
NHMRC Project Grant
• How Burkholderia evades autophagy, Boyce/Devenish/
Prescott (2009–2011).
ARC Centre of Excellence Grant
• Centre of Excellence in Structural and Functional
Microbial Genomics, Adler/Coppel/Devenish/Hertzog/
Meeusen/Rood/Rossjohn/Smith/Whisstock (2010–2013).
Transmission electron micrograph of RAW264.7 cells six hours
after infection with Burkholderia pseudomallei (magnification
x600). Intracellular bacteria are observed within single-membrane
compartments and not double-membrane autophagic compartments.
www.med.monash.edu.au/microbiology/staff/cooke.html
www.med.monash.edu.au/biochem/staff/devenish.html
Professor John Davies
Head, Department of Microbiology
(to October 2011)
Molecular Analysis of Bacterial Pathogens
By studying bacteria that cause infectious
diseases in humans and animals, we are
working to understand how bacteria and
their hosts respond to each other during
infectious processes.
Research Fellow
Dr Catherine Ryan
Research Assistant
Ms Chen Ai Khoo
PhD Students
Mr David Allen
Ms Ya-Hsun Lin
Ms Dervilla McGowan
Ms Jessica Phillipps
• Regulation of pilus biogenesis in Neisseria (2009–2011).
Research Assistant
Ms Kher Shing Tan
PhD Students
Mr. Jhih-Hang Jiang
Ms Janette Tong
Honours Students
Ms Dilini Alankarage
Mr Nicholas Clark
Mr Sam Palframan
www.med.monash.edu.au/microbiology/research/davies.html
54
Mitochondria are essential for the function of our cells.
These structures are the powerhouses of the cell, providing
the ‘cellular fuel’, ATP. In human cells, mitochondria also
regulate other processes, including controlling when a cell
self destructs and dies. Failure in mitochondrial processes
can cause cancer, and metabolic and neurodegenerative
disorders.
• Characterisation of Neisserial cell surface adhesins and
their role in infection (2009–2011).
Neisseria gonorrhoeae.
Dr Kip Gabriel
We study how mitochondria are impaired
during disease.
NHMRC Project Grants
Disease-causing or pathogenic bacteria inhabit specific sites
in the body. They may then invade the host tissue and enter
the bloodstream, where they continue to multiply. At each
stage, bacteria need to alter the cell surface by switching
specific genes on or off. For instance, bacteria produce
surface structures to initially latch onto their host, which they
may later discard when invading tissues. Also, other bacterial
surface components must be present in the bloodstream for
bacteria to avoid immune detection.
Complete DNA sequences of many pathogenic bacterial
genomes are now known. From this information, we can
identify genes present in given species, monitor their levels at
specific infection stages and understand how these genes
are controlled. We can also monitor how the immune system
responds to changes on the bacterial cell surface.
By understanding these complex interactions, it may be
possible to identify new and innovative ways of interfering
with infection processes.
Mitochondrial Functional and Disease Biology
It is now clear that many human pathogens have evolved
to ‘hijack’ or ‘disrupt’ mitochondrial processes during
infection by sending toxic proteins to these structures.
Together with our collaborators, we are investigating
how mitochondrial function is regulated by bacteria that
cause stomach ulcers and meningococcal disease.
We also study mitochondrial dysfunction in early and
late-onset Parkinson’s disease.
NHMRC Project Grants
• Helicobacter pylori VacA toxin: modulation of human
mitochondrial function by a bacterial pathogen, Gabriel/
Kwok-Schuelein (2011–13).
A mammalian cell showing the endoplasmic reticulum (green) and
mitochondria (red).
• How does inactivation of PINK1 cause Parkinson’s
disease? Cheng/Culvenor/Gabriel (2009–2011).
www.med.monash.edu.au/biochem/staff/gabriel.html
55
Annual Report 2011
Infectious Diseases
Nuclear Signalling Lab
We study the movement inside cells of proteins
from viruses that cause Dengue fever, rabies,
respiratory disease and AIDS, as well as
molecules that play a role in cancer.
We are interested in how these medically relevant proteins
move into and out of the cell nucleus, the control centre of
the cell, how this can be controlled, and how drugs can be
targeted to the cell nucleus to combat cancer or correct
genetic defects.
Research Fellows
Dr Mohammad Aljofan
Dr Leon Caly
Dr Johanna Dean
Dr Greg Moseley
Dr Stephen Rawlinson
Dr Kylie Wagstaff
Research Assistants
Ms Rebecca Davies
Mr Steve Heaton
Mr Bevan Hirst
PhD Students
Ms Arelia Aguilar (visiting)
Ms Michelle Audsley
Ms Shadma Fatima
Ms Henna Kuusisto
Ms Kim Lieu (completed)
Mr Ivan Ng
Ms Sibil Oksayan
Ms Caitlin Rowe
Ms Linda Wiltzer
Honours Students
Mr Aaron Brice
Mr Callum Lawrence
In 2011, we showed that particular nuclear transport proteins
play a key role in embryonic stem cell development and drive
germ cell differentiation in the testis. We also determined the
mechanism that cancer related molecules and some viral
components use to be transported into the cell nucleus.
Importantly, we developed a strategy to identify new
inhibitors of nuclear transport, showing that they can inhibit
the replication of viruses such as HIV, the causative agent of
AIDS, and Dengue.
• Novel technology platform for gene delivery into intact
cells, Wagstaff (2011–2013).
• New targets for antiviral therapies, Jans/Moseley/Wang
(2011–2013).
ARC Postdoctoral Fellowship
• Dr Wagstaff (2011–2013)
Bill and Melinda Gates Foundation Grand
Challenges Grant
• Viral self-destruct sequences: a novel live-vaccine
technology, Moseley/Rawlinson/Jans (2010–2011).
Recently, we discovered the following:
Senior Collaborator
Professor Julian Rood
Research Fellows
Dr Milena Awad
Dr Glen Carter
Research Assistants
Ms Anjana Chakravorty
Ms Michelle Kelly
Technical Officers
Ms Pauline Howarth
Ms Julie Singleton
• Professor Jans (2011–2015).
PhD Student
NHMRC Project Grants
• Regulation of subcellular localisation of respiratory
syncitial virus M protein: Implications for pathology,
Jans/Ghildyal/Bardin (2010–2012).
We have developed novel ways to genetically
modify the bacterial pathogens Clostridium
difficile and Clostridium sordellii of both human
and animal origin. We are using this approach
to understand how these micro-organisms
harness regulatory and virulence factors to
cause disease.
ARC Discovery Grants
NHMRC Senior Principal Research Fellowship
• Subcellular trafficking of P proteins of human pathogenic
viruses: roles in viral pathogenicity and targeting for
therapeutics, Moseley (2011–2013).
Clostridial Genetics Laboratory
Professor David Jans
Mr Edward Rose
Honour Students
‘Fast-track’ nuclear transport by the cancer protein PTHrP.
PTHrP moves rapidly along microtubules until it reaches the microtubule
organising centre (MTOC), where the importin β (β) transporter takes
over, and moves PTHrP through the nuclear pore (NPC) into the nucleus.
Ms Bliss Cunningham
Ms Darshani Jayawardena
Ms Lucy Li
Ms Rebecca Rabi
Laboratory Associate
Dr Priscilla Johanesen
• Nuclear function of Dengue NS5 protein: Role in disease,
Jans/Akkina (2010–2012).
• Novel microtubule association sequences from rabies
virus: Subversion of antiviral responses and use in drug
delivery, Jans (2009–2011).
Our lab studies how protein molecules are
precisely transported to their correct location
within cells.
Professor Trevor Lithgow
Research Fellows
Dr Matthew Belousoff
Dr Denisse Leyton
Dr Thomas Naderer
Dr Hsing-Hui Shen
Dr Miguel Shingu-Vasquez
Dr Chaille Webb
PhD Students
Ms Khatira Anwari
Ms Nermin Celik
Mr Srgjan Čivčiristov
Mr Rhys Dunstan
Ms Victoria Hewitt
Mr Joel Selkrig
Professor Trevor Lithgow
ARC Super Science Fellowship
• Design and fabrication of molecular machines:
The nanomachines of the future (2011–2013).
56
Research Fellows
Dr Rob Bischof
Dr Melissa Burke
Dr Michael de Veer
Dr David Piedrafita
Dr Jill Pleasance
Protein transport is central to understanding how diseasecausing microbes build their outer membranes and how they
direct toxic proteins into human cells. Protein targeting and
transport are both driven by complex molecular machines.
Research Assistants
Mr Chris Hosking
Mr Gary Nguyen
Our research addresses how these specialised protein
transport machines evolve and the mechanisms by which
these transport machines function.
PhD Students
NHMRC Program Grant
• NHMRC program in cellular microbiology (2011–2015).
NHMRC Project Grant
• Determining how the ability to secrete proteins assists
E. coli to cause disease (2009–2011).
ARC Federation Fellowship
• Molecular machines that drive microbial pathogens
(2008–2013).
www.med.monash.edu.au/biochem/staff/lithgow.html
• We have developed methods by which a pathogen
of post-abortive and postpartum females and
transplant patients, Clostridium sordellii, can be
genetically manipulated. We have shown that the
bacterium contains a lethal toxin, TcsL, that is the
primary cause of severe disease symptoms; and
• Regulation of toxin production in Clostridium difficile,
Rood/Lyras (2009–2011).
• Virulence mechanisms in hypervirulent epidemic strains
of Clostridium difficile, Lyras/Rood/Johnson/Gerding
(2009–2011).
ARC Discovery Grant
• The role of virulence factors of Clostridium difficile
in food production animals, Lyras/Rood/Riley/Songer
(2010–2012).
ARC-Linkage Grant
• The development and evaluation of colostrum-derived
antibodies for the prevention and treatment of
Clostridium difficile infections, Lyras/Rood/Rawlin
(2011–2014).
• Spores of epidemic hypervirulent strains of bacteria
have different surface properties compared to
non-epidemic strains, which may play important
roles in infection and disease since spores are
responsible for infection initiation.
NHMRC Project Grants
• Host-pathogen interactions in gas gangrene,
Rood/Lyras/Awad (2011–2014).
Transmission electron microscopy image of Clostridium difficile spores.
Biotechnology Research Laboratories
A major global issue is the rise of antibiotic resistance in
bacterial pathogens. In response to this threat, new drug
targets need to be identified and new vaccines need to be
developed. Fundamental aspects of bacterial cell biology
need to be understood if we are to take creative approaches
to defeating these 'new' bacterial pathogens.
ARC Federation Fellow
• Mutations in a regulatory gene encoding TcdC are
important in development of the hypervirulent phenotype
in Clostridium difficile and Clostridium sordellii;
• How does Clostridium sordellii cause disease in
post-abortive, post-partum and transplant patients?
Lyras/Rood/Aronoff (2010–2012).
www.med.monash.edu.au/microbiology/research/lyras.html
www.med.monash.edu.au/biochem/research/projects/nuclearsig.html
Protein Targeting Laboratory
• Toxin B from Clostridium difficile plays an essential
role in antibiotic-associated infections in hypervirulent
strains of bacteria;
Dr Dena Lyras
After some controversy, our model (the 'inside view') is now accepted as
the mechanism that human mitochondrial cells have used to evolve from
distant bacteria. The major innovations that drove this development took
place within the bacterial genome. Reproduced with permission from
Alcock et al. Science. 2010. 327: 649–650.
Ms Jenna Van Gramberg
Mr Chris Hosking
Mr Michael Lees
Mr Hamish McWilliams
Ms Jacqueline Melville
Ms Sarah Preston
Masters Students
Ms Bahar Liravi
Ms Trine Meldgaard
Honours Students
Mr Jibril Ibrahim
Mr David Lewis
Mr Minh Hung Nguyen
Professor Els Meeusen
We conduct basic and applied research in
infectious and allergic diseases with the aim
to develop new vaccines, diagnostics and
treatments.
ARC Centre of Excellence Grant
Helminth (worm) parasites cause debilitating diseases
in people living in developing countries and significant
production losses in livestock worldwide. However, there are
no vaccines that target these parasites. We have identified a
key parasite molecule (antigen) that can provide protection
against infection. In collaboration with a major industry
partner, we have shown that a vaccine based on this antigen
can be used in sheep under farm conditions, and are further
developing this vaccine for commercial application.
ARC Discovery Grant
Vaccines also need to be delivered effectively and generate
immune responses following injection. By using a unique
lymphatic cannulation model, we can now study how
antigens flow and are taken up from the injection site
by different adjuvants - immune-enhancing agents. By
understanding how these adjuvants work, we can design
vaccines to treat infectious diseases and allergies.
• ARC Centre of Excellence in Structural and Functional
Microbial Genomics, Adler/Coppel/Devenish/Hertzog/
Meeusen/Rood/Rossjohn/Smith/Whisstock (2010-2013).
• Molecular determinants of an allergic response,
Meeusen/O’Hehir (2009-2011).
ARC Linkage Grants
• Characterisation and development of adjuvants for new
generation veterinary and human vaccines, Meeusen
(2009-2011).
• Development of proto-type vaccine against
gastrointestinal nematode larvae, Meeusen (2006-2011).
Ministry of Science and Education, SPAIN – National
Grant
• In vivo depletion of γδT cells and eosinophils and its
effects on the resistance of the Canaria Hair Breed sheep
against Haemonchus contortus, Gonzalez/Piedrafita/
Meeusen/Molina/Rodriguez/Hernandez (2009-2011).
With our collaborators at the Alfred Hospital and Faculties of
Engineering and Pharmacy, we are testing new formulations
and delivery devices, and developing new diagnostics for the
treatment of asthma and other respiratory diseases.
NHMRC Development Grant
• The Respire™ system: Portable pulmonary delivery
platform for rapid, flexible and highly efficient treatment of
elderly, paediatric and physically-compromised patients
with chronic respiratory diseases, Yeo/ Friend/Morton/
McIntosh/Meeusen (2010-2011).
www.med.monash.edu.au/physiology/brl/
Uptake of antigen by different cell types (coloured) after vaccination.
57
Annual Report 2011
Infectious Diseases
Molecular Virology
We develop modified virus-like particles
as vaccination tools and assess their mode
of action.
Virus-like particles (VLPs) have emerged as successful
devices for developing modern vaccines. They are
non-infectious multi-protein complexes which elicit
highly effective immune responses.
Senior Research Fellow
Dr Gholamreza Haqshenas
Research Fellow
Dr Wan-Shoo Cheong
PhD Student
Ms Michiko Hyakumura
Honours Students
Mr Minh Gau
Ms Natalie Kingston
We design modified viral structural proteins containing
immune system-stimulating sequences derived from
foreign sources. We assess how these recombinant
proteins assemble into highly structured multi-protein
complexes (VLPs), and study mechanisms of immunogen
processing and how long-acting immune responses can
be achieved. We have successfully generated VLPs that
induce immune responses against the viruses: hepatitis
C (HCV), HIV and influenza.
We have also identified genetic interactions that occur
between key proteins during HCV synthesis. As these
protein-protein interactions are attractive targets for antiviral
compounds, we are developing screening assays to identify
inhibitors which interfere with HCV synthesis.
• Recombinant virus-like particles for the delivery of HIV-1
neutralising epitopes arrayed at high density (2010–2011).
• High throughput screening assays for the examination of
potential inhibitors of hepatitis C virus p7 (2010–2011).
Research Fellow
Equity Trustees, Harold and Cora Brennen
Benevolent Trust
PhD Students
• Particles with modified structural features as optimised
delivery platforms for HIV neutralising sequences (2011).
We use molecular genetics to understand how virulence
factors are regulated, and how virulence and antibiotic
resistance genes move between bacteria. We aim to
understand bacterial evolution and pathogenesis, and
develop new methods to control and treat bacterial
infections in both humans and animals.
Senior Collaborator
Recently, we discovered the following:
Research Fellows
• The crystal structure of four proteases from the footrot
pathogen, a hoof infection in sheep, goats and cattle;
Visiting Scientists
A/Prof. Xiang-Dang Du
Dr Marianne Gilhuus
PhD Students
Mr Daniel Andrews
Ms Shalini Narayanan
Mr Abolghasem Tohidpour
The peptidoglycan-binding domain of Helicobacter pylori motility protein
B, a component of the bacterial flagellar motor.
Department of Innovation, Industry, Sciences and
Research, Australia-India Biotechnology Collaborative
Fund Project Grant
Cancer Council Victoria
• Clostridium-directed enzyme prodrug therapy
(2010–2012).
• Molecular recognition between alkane hydroxylase and
rubredoxin in alkane degrading bacteria (2010–2013).
Australian Poultry CRC
• Vaccine against Clostridium perfringens to protect birds
from necrotic enteritis (2010–2012).
www.med.monash.edu.au/microbiology/staff/roujeinikova.html
US National Institutes of Health
Norwegian Research Council
Fungal Pathogenesis Laboratory
Dr Ana Traven
We study how the hospital-acquired human
pathogen Candida albicans makes its cell
surface, which plays a key role in the
disease process.
NHMRC Project Grants
• Host-pathogen interactions in Clostridial myonecrosis,
Rood/Lyras/Awad (2011–2014).
• Role of regulatory genes in the control of toxin production
in Clostridium perfringens (2009–2011).
• Regulation of toxin production in Clostridium difficile,
Rood/Lyras (2009–2011).
Research Fellows
Dr Branka Jelicic
(European Group of Eight fellow)
Dr Yue Qu
• Virulence mechanisms in hypervirulent epidemic strains
of Clostridium difficile, Lyras/Rood/Johnson/Gerding
(2009–2011).
PhD Students
Mr Farkad Bantun
(with Dr Anton Peleg)
Ms Tara Quenault
Ms Nathalie Uwamahoro
• (2006–2013)
• The role of virulence factors of C. difficile in food animals
Lyras/Rood/Riley/Songer (2010–2012).
We are also interested in the mechanisms that Helicobacter
pylori use to cause gastric disease. In collaboration with
Dr Terry Kwok-Schuelein, we are analysing the structure of
CagA and its role in stomach cancer formation.
• Understanding the molecular mechanism of force
generation in the bacterial flagellar motor (2010–2014).
• The toxin that causes the poultry disease necrotic
enteritis is encoded on a conjugative plasmid.
ARC Discovery Grant
We investigate structure-function relationships in motility
protein B, the component of the bacterial flagellar motor
(BFM). Many pathogenic bacteria use motility as a
mechanism to spread in the host organism and cause
disease. However, there is limited structural information
about motility proteins that control flagellum rotation, which
we hope to address. We have recently established how
the power-generating part of the BFM anchors itself to the
cell wall. We are now working to understand the molecular
mechanism of force generation.
ARC Discovery Project (linked with Australian
Research Fellowship)
• The development and evaluation of colostrum-derived
antibodies for the prevention and treatment of
Clostridium difficile infections, Lyras/Rood/Rawlin
(2011–2014).
• Ovine footrot and contagious claw diseases in Norway
(2010–2014).
ARC Centre of Excellence in Structural and Functional
Microbial Genomics
Associate Professor Roujeinikova
• Japan Society for the Promotion of Science Fellowship.
• (2010–2014)
ARC Linkage Grant
• A novel regulatory gene that modulates virulence in the
bacterium that causes gas gangrene; and
Honours Students
Awards and Achievements
ARC Australian Research Fellowship
Professor Julian Rood
• Clostridium perfringens type B, C, D toxins (2009–2014).
• The pathogenesis of infections caused by Clostridium
sordellii Lyras/Rood/Aronoff (2010–2012).
Associate Professor Anna Roujeinikova
Bacterial stress response also plays a role in disease.
Together with Professor John Davies, we aim to understand,
at both the molecular and structural levels, how the stress
response is initiated in Neisseria gonorrhoeae.
• These proteases are important virulence factors in
ovine footrot;
Ms Rachel Adamson
Ms Radhika Bantwal
Ms Anjana Chakravorty
Ms Jocelyn Choo
Mr Thomas Hiscox
Ms Lee-Yean Low
Ms Kate Mackin
Mr C. Benjamin Wade
Ms Lakmini Weeramantri
Ms Jessica Wisniewski
Ms Xu-Xia Yan
Ms Chai Yee Kua
Ms Shelley Lyon
Mr Christopher Stubenrauch
Dr Hernan Alonso
www.med.monash.edu.au/microbiology/research/netter.html
We study how bacterial pathogens, particularly
anaerobic bacteria, cause disease in humans
and animals.
Dr Vicki Adams
Dr Luminita Badea
Dr Trudi Bannam
Dr Jackie Cheung
Dr Xiaoyan Han
Dr Ruth Kennan
Dr Versha Rai
We use a structural biology approach to
understand how medically-important bacteria
cause disease.
Australian Centre for HIV and Hepatitis Virology
Research
Functional Biology of Bacterial Pathogens
Dr Dena Lyras
Structural Biology of Bacterial
Virulence Factors
Associate Professor Hans Netter
Structure of AprV2 protease from Dichelobacter nodosus, reproduced
from Kennan et al., PLoS Pathogens, 2010. 6: e1001210.
The cell wall is a structure on the surface of C. albicans’
cells, which is required for adherence to indwelling medical
devices such as catheters, pacemakers and prosthetic
devices, leading to the formation of drug-resistant fungal
biofilms. Biofilms are highly resistant to antifungal therapy,
resulting in high death rates in infected individuals. In addition
to making biofilms, the cell wall also interacts with, and
evades the patient’s immune system.
We have identified a new system network that links cell
wall integrity and antifungal drug resistance in C. albicans
with the function of the mitochondria, the powerhouse of
eukaryotic cells. This discovery has allowed us to identify
new factors which are implicated in the resistance of C.
albicans to existing antifungal drugs, and which could
therefore be targeted for future drug discovery programs.
We have also discovered new C.albicans’ genes that are
involved in biofilm development.
Scanning electron microscopy image of C. albicans biofilms formed on
serum-coated silicone disks.
ARC Discovery Project Grant
www.med.monash.edu.au/microbiology/research/rood.html
58
• RNA-binding proteins regulate protein targeting and
membrane biosynthesis, Traven/Lithgow (2010–2012).
www.med.monash.edu.au/biochem/staff/traven.html
59
Medical Imaging and Radiation Sciences
Diagnostic Imaging and Radiation Therapy
Medical Imaging
and Radiation
Sciences
>> Diagnostic imaging: X-Ray,
Ultrasound, CT, MRI and PET
>> Functional imaging of cancer
Research Assistant
Ms Dianne Luc
MPhil Students
Dr Jeremy Graham
Mr Mark Ngo
Mr Richard Oates
Mr David Robinson
PhD Students
Mr Nigel Anderson
Mr Jason Callahan
Ms Shawna Farquharson
Mr Brian Lee
Mr Paul Lombardo
Mr Jonathan McConnell
Ms Erica Sturm
Dr John Troupis
Ms Caroline Wright
Dr Michal Schneider-Kolsky
Our group collaborates with clinical and
academic centres to develop and test new
applications in medical imaging and radiation
therapy techniques, including X-Ray, CT, MRI,
PET and ultrasound. We focus on anatomical
and functional cancer detection (breast, lung,
head and neck and prostate), musculo-skeletal
ultrasound, developing new contrast materials
for use in ultrasound, and study biological
effects of neonatal cranial ultrasound.
In 2011, the group initiated various research studies utilising
infra-red thermal imaging for applications in human and
animal models.
Projects are also ongoing in education, occupational
burnout, professionalism and role extension of
radiographers and radiation therapists.
Awards and achievements
Mr Jason Callaghan
• CRC Biomedical Imaging Scholarship (2011-2012).
FDG PET/CT scans in a patient with a suspected liver tumour. The top
row shows a 4D PET/CT scan compared to the standard PET/CT scan
on the bottom row. The 4D PET/CT scan shows a large metabolically
active tumour indicated by the cross-hairs. This large tumour was not
visible on the standard PET/CT scan. This example shows that 4D
scanning can successfully correct for a significant artefact caused by
respiratory motion.
www.med.monash.edu.au/radiography/research
Radiation therapist Sarah Everitt treating a patient with radiation therapy.
61
Neuroscience
Understanding how the brain
interacts with the environment
and how it communicates with
and controls the tissues and
organs of the body
>> What changes occur in the brain after
a stroke?
>> How does the brain interact with hormones
in fertility, obesity and stress?
>> How do adverse events during pregnancy
and birth affect a child’s long-term health?
>> How does the brain respond to vision
and sound?
Nerve cell projections expressing the peptides kisspeptin (green/yellow),
neurokinin B (red/yellow) and gonadotrophin releasing hormone (blue)
converge at the median eminence, at the base of the brain.
Image: Dr Jeremy Smith.
Annual Report 2011
Neuroscience
Sensory and Cognitive Neuroscience
Laboratory
Sensory Neuroscience
Dr Kathleen Burman
We are interested in understanding the nature
of the plastic changes that occur in the adult
brain after a stroke.
Research Assistant
Ms Karyn Richardson
When a stroke occurs, blood supply to part of the brain is
blocked (ischemia), and affected brain cells die from oxygen
and glucose starvation. Many stroke victims recover, either
partially or completely, suggesting that changes occur that
allow undamaged parts of the brain to control function by
compensating for the damaged regions.
With our stroke research, we study the structural changes
that occur in the neural pathways connecting parts of the
brain that receive sensory information and the motor areas
that then use this information to plan and execute motor
commands, after focal ischemic lesions of the primary motor
cortex. We are restricting the lesions to this part of the brain
because it is the principal region that sends nerve impulses
to the spinal cord to accomplish movement.
Since there is evidence to suggest a relationship between
anatomical changes and functional recovery after stroke, we
are also studying whether rehabilitative training can improve
physical recovery.
Research Fellow
Dr Leo Lui
Research Officers
As part of a study on changes in the motor control pathways
following stroke, anatomical tracers are injected into motor areas
to track reorganisation of the normal pathways. Here we see cells
in the non-lesioned primary motor cortex labelled following injection
of a fluorescent tracer in a secondary motor area.
Research Fellows
Dr Jessica Jacobi (50%)
Dr Qun Li (33%)
Dr Rui Zeng
Research Assistants
Ms Teena George
Ms Alda Pereira (50%)
Ms Alix Rao (50%)
Ms Sofie Saleh (50%)
PhD Students
Dr Kevin Kwok-Lee (MBBS)
Dr Matthew Maiden (MBBS)
(Co-supervisor, Adelaide
University)
Mr Steven Yau
(Co-supervisor, University
of Melbourne)
The brain controls hormone secretion from the pituitary
gland. In turn, pituitary hormones regulate the function of
the endocrine organs: ovaries, testes and adrenal glands.
The part of the brain that communicates to the pituitary
is the hypothalamus, which also plays a major role in
controlling body weight.
Dr Markus Hietanen
Dr Lauretta Passarelli
A/Prof Vahid Sheibani
Ms Claire Annunziata
Mr Tristan Chaplin
Mr Greg Egan
Ms Karyn Richardson
Ms Amanda Worthy
Ms Katrina Worthy
• Plasticity of sensorimotor representations in adult
primate cortex (2009–2011).
Neuroendocrinology is a discipline that relates
to the way that the nervous system interacts
with and controls the endocrine (hormonal)
system of the body. We study how the brain
controls reproduction and food intake. This
has relevance to fertility and obesity.
Visiting Scientists
Research Assistants
NHMRC Project Grant (New Investigator)
Systems Neuroendocrinology
Dr Vladimir Dubaj
Dr Saman Haghgooie
Dr David Reser
Dr Richa Verma
Dr Hsin-Hao Yu
Professor Iain Clarke
Head, Department of Physiology
United States Department of Agriculture
We study how the brain processes sensory
information, and how this changes as result
of experience. We hope to generate a
comprehensive series of ‘circuit diagrams’ of
the sensory regions of the mammalian brain,
which will help us understand how nerve
cells communicate, via electrical signals,
what we feel from moment to moment. By
understanding these basic brain functions,
there is the potential to develop environmental
sensors in machines and prosthetic devices
that can restore or enhance sensory functions
in humans.
ARC Discovery Grants
• Computational neuroanatomy: Analysis of neural
connections in the primate brain, Rosa/Mitra (2011-2013).
• Colour visual processing in honeybees: Solutions for
decision making in complex environments, Dyer/Rosa
(2008-2012).
• Understanding how the primate brain processes visual
information (2008-2010).
ARC Special Research Initiative Grant (Research in
Bionic Vision Science and Technology)
• Direct stimulation of the visual cortex: A flexible strategy
for restoring high-acuity pattern vision, Lowery/Rosa/
Rosenfeld/Rajan et al., (2010-2013).
In 2011, we used electrophysiological techniques to obtain
the first recordings of neuronal activity in prostriata, a
phylogenetically ancient area of the primate cerebral cortex,
about which very little is known. Our results demonstrate
that this structure ‘fast-tracks’ information from the eyes
to brain regions involved in movement, emotions, memory
and hearing. It appears that prostriata works as an ‘alert
system’, focussing the brain on new and unexpected events
occurring in the periphery of the visual field.
NHMRC Project Grants
• A visual pathway through the limbic cortex (2011-2013).
• Physiological bases of audiovisual integration,
Rosa/Rajan (2009-2011).
PhD Student
Dr Yin Yang
• Saccadic eye movements and the neural basis of visual
perception, Ibbotson/Rosa (2009-2011).
Honours Students
• Plasticity of the primate cerebral cortex (2008-2010).
Ms Amanda Davies
Mr Thomas Wicaksono
Professor Marcello Rosa
NHMRC Enabling Grant (Model Biological Systems)
• National non-human primate breeding and research
facility, Phelps/Borg/Rosa/Smith (2007-2011).
Computer graphic ‘unfolded’ reconstruction of the cerebral cortex of
the macaque, showing the spatial distribution of neurones that send
connections to area V6Av, a part of the brain that provides visual
information for the control of hand movements towards objects. Area
V6Av receives most of its inputs from visual areas (V2, V3, V4/DP and
MST), and from other areas involved in visual-motor coordination (MIP,
PGm, FEF, area 46). The insert is a dorsal view of the intact macaque
brain. This study was conducted in collaboration with researchers from
the University of Bologna, Italy.
• Hypothalamic site of action of kisspeptin in the regulation
of growth hormones release in ruminants, Clarke (2011).
German Research Community (DFG)
www.med.monash.edu.au/physiology/staff/rosa.html
• Characterisation of the skeletal effects of the
disconnection between the hypothalamus and the
pituitary gland in sheep, Clarke/Amling/Pogoda/Beil
(2010–2011).
Awards and Achievements
Professor Clarke
• Appointed fellow of the Society for Reproductive Biology.
We study two neuropeptides that regulate both energy
homeostasis and reproduction: Kisspeptin and gonadotropin
inhibitory hormone. In other work, we are examining how the
brain controls the expenditure of energy by fat and muscle to
overcome obesity.
NHMRC Project Grant
• Melanocortin regulation of reproduction, Clarke/Smith
(2009–2011).
ARC Project Grant
• Dissecting the impact of stress on reproduction: Novel
peptide mediates as inhibitory effects of stress on female
reproduction, Tilbrook/Clarke/Hemsworth (2009–2011).
University of Mexico Fellowship
• Dr Jessica Jacobi (2009–2011).
Horizon Science Contract
Model showing how cells in the brain interact to regulate appetite and
reproduction. From Backholer et al., Endocrinology, 2010. 150: 5488.
• Beneficial effects of LoGiCane sugar on glycemic index
adiposity and insulin sensitivity in maturing piglets:
Implications for human childhood obesity, Clarke
(2010–2011).
www.med.monash.edu/physiology/staff/clarke.html
64
65
Annual Report 2011
Neuroscience
Cell Systems Physiology
We focus on understanding how adverse
events during pregnancy and birth give rise
to diseases in the baby, which remain
throughout life.
NHMRC Project Grants
We investigated the effects of maternal alcohol
consumption during pregnancy on the function of blood
vessels in the offspring, using a sheep model. Alcohol use
alters cardiovascular function significantly, affecting arteries
and blood pressure control mechanisms (Image: Panel A).
• Understanding local and regional determinants of EDHF
and NO dysfunction in resistance arteries in diabetes
(2009–2012).
We also study how smooth muscle contraction in the
ureter is controlled. Problems in pregnancy can result in
obstructed urine flow from the kidney to the bladder in
new-born infants. We are interested inhow prostaglandins
influence pacemaker ion channels, which are responsible
for these contractions (Image: Panel B).
Research Fellows
Dr Jessica Jacobi (50%)
Dr Kelly Kenna
Dr Qun Li (33%)
Research Assistants
Ms Meagan Davies
Ms Mary Tonta
PhD Students
Mr Justin Bourke
Mr Shane Chaisakul
Ms Melissa Tjongue
Oxygen deprivation can occur during the process of
birth and result in cognitive and motor deficits in children.
The hippocampus is a brain region critical for memory
and learning, and is very vulnerable to hypoxia. We found
that oxygen deprivation in marmosets had no effect on
hippocampal function in females, but function in males
was significantly impaired (Image: Panel C).
Sensory Neuroscience
Associate Professor Helena Parkington
Dr Richard Lang
Dr Harold Coleman
Dr Marianne Tare
• How neurosteroid hormones may protect the brain
following compromised pregnancy and preterm birth
(2011–2013).
• How amyloid causes neurodegeneration: The role of
transthyretin in familial amyloidotic polyneuropathy
(2009–2011).
Postdoctoral Fellow
Dr Scott Kolbe
Research Assistants
Ms Gemma Edwards
Ms Danielle Prescott
ARC Linkage Grant
Our lab investigates the neuronal activity
in the brain that underlies conscious visual
perception.
NHMRC Project Grant
We record the activity of single neurons in parts of the brain
that respond to visual stimuli. By recording data in awake
subjects, who can indicate what they perceive, we are
able to understand how the brain encodes and assesses
the external environment, and how brain activity leads to
conscious perception.
Human Frontier Science Program: Career
Development Award
• Neuronal sensitivity and variability underlying perception
and action (2011–2013).
• Changing sensitivity in a changing world: How do
neuronal populations encode dynamic environments?
(2010 –2012).
In 2011 we investigated how visual perception is affected
by recently seen stimuli. We have shown that judgments
of motion direction at any point in time are affected by the
speed and direction of stimuli seen in the previous few
seconds. This indicates that our basic visual sensations are
highly malleable and subject to ongoing calibration.
The lab is also part of the Monash Vision Group,
a cross-faculty initiative involving industry partners that
aims to develop a bionic eye. We are pre-clinically testing
prostheses to determine how to optimally stimulate the
brain’s visual cortex to recreate vision in blind patients.
• Novel anti-ageing peptides in the vascular system.
NHF Grants-in Aid
• Alcohol in pregnancy leads to artery disease in the
offspring (2009–2011).
University of Mexico Fellowship
• Dr Jessica Jacobi (2009–2011).
www.med.monash.edu.au/physiology/staff/price.html
Premature labour results in the baby being born early
and predisposes to complications in later life. We record
uterine contractions and electrical activity in tissue obtained
from women undergoing caesarean delivery. We have
discovered that a particular potassium channel that is
involved in suppressing uterine contractions is turned
off during labour (Image: Panel D).
Sensory Neuroscience
Honours Students
Mr Wilfred Angkawijawa
Mr Jibriil Ibrahim
Ms Rushita Kalidindi
Mr Michael Nguyen
Ms Anabella Reaper
Mr Victor Suturin
Research Officers
Dr Vladimir Dubaj
Dr Saman Haghgooie
Dr Chun Wang
Visiting Scientists
Prof Gunter Ehret
Prof Peter Thorne
Research Assistants
Mr Justin Bourke
Ms Kahli Cassells
PhD Students
Ms Emma Brunton
Ms Duwage Dasuni Alwis
Ms Collette Mann
Mr Nathan Smith
www.med.monash.edu.au/physiology/research/smoothmuscle/index.html
66
Dr Nicholas Price
Associate Professor Ramesh Rajan
We examine different aspects of sensory
processing in the brain using animal and
human models.
NHMRC Project Grant
We record electrical signals of nerve cells in animal models
to examine what happens to the brain’s sensory areas
when there is traumatic brain injury as occurs following
car or sporting accidents. We have shown that brain injury
causes specific brain sensory processing deficits, which
could explain why affected individuals have cognitive and
movement problems.
ARC Special Research Initiative Grant (Research in
Bionic Vision Science and Technology)
• Physiological bases of audiovisual integration,
Rosa/Rajan (2009–2011).
• Direct stimulation of the visual cortex: A flexible strategy
for restoring high-acuity pattern vision, Lowery/Rosa/
Rosenfeld/Rajan (2010–2013).
In human models we study how the brain extracts
information from 'noise', in both normally developing
people and those with Autism spectrum disorders.
We showed that time of language acquisition impacts on
academic performance and how developmental setbacks
can be overcome. Our findings will impact on the design
of assessments for diverse student populations in tertiary
institutions. We have also linked speech processing
difficulties in high-functioning autistic people to hearing
problems.
We continue to participate in the Monash Vision Group,
a University initiative focussed on developing bionic
technologies to restore vision in blind patients. Currently,
we are testing in animal models the first prototypes of
a 'bionic eye' based on direct stimulation of the
cerebral cortex.
www.med.monash.edu.au/physiology/staff/rajan.html
67
Annual Report 2011
Reproductive Neuroendocrinology
Dr Jeremy T Smith
We study the mechanisms and pathways
within the brain that control fertility. Our group
is also aiming to develop new strategies for
the treatment of infertility.
Research Fellow
Dr Qun Li (33%)
Research Assistants
Ms Alda Pereira (50%)
Ms Alix Rao (50%)
Ms Sophie Saleh (50%)
Honours Student
Ms Julie-Ann De Bond
Reproduction is complex process, which is controlled by
three key ‘players’: the brain, pituitary gland and testis or
ovaries. At the top of this hierarchical regulatory system
is gonadotrophin-releasing hormone (GnRH), which is
produced and secreted from the preoptic area of the brain.
This molecule is a chemical master switch that triggers the
onset of puberty and regulates key reproductive hormones:
luteinising hormone and follicle stimulating hormone. These
hormones (also called gonadotrophins) circulate in the
peripheral blood to stimulate the gonads (testis or ovaries).
The precise mechanisms that control GnRH secretion were,
until recently, unknown.
We have demonstrated that a novel protein in the
brain, Kisspeptin, is a critical regulator of GnRH, the
gonadotrophins and fertility.
NHMRC Project Grant
• Kisspeptin and its receptor mastermind reproduction
(2010–2012).
ARC Future Fellowship
• Masterminding reproduction: Kisspeptin and
RFamide-related peptide (2009–2013).
Monash Researcher Accelerator Program
• (2011–2012)
Kisspeptin neurons (red) and neurons labelled with a neuronal tracer
dye (BDA, green) in the arcuate nucleus of the brain. Insert shows
a higher magnification image of kisspeptin, GnRH (blue) and BDA
labelled neuronal terminals in the exterior zone of the median
eminence ‘on route’ to the pituitary gland.
Awards and Achievements
Dr Smith
• Joint winner of the 2011 Newcastle Reproduction
Emerging Research Leader Award, Society for
Reproductive Biology.
Behavioural Neuroendocrinology
Research Assistant
Ms Sara Drew
PhD Students
Ms Joanna Engle
Mr Adam Morrissey
Mr Cameron Ralph
Ms Bronwyn Stevens
We investigate how stress impacts body
function and behaviour in animals and humans,
and the effect of environmental factors on milk
production in goats and sheep.
NHMRC Project Grant
In collaboration with researchers at the University of
Michigan, in the US, we have shown that social stress
suppresses the secretion of reproductive hormones and
sexual behaviour in sheep. We have also established that
the stress hormone cortisol plays an important role, where
it acts both within the brain, and externally, in the pituitary
gland. In collaboration with researchers at the University of
Melbourne, we have discovered that the amount of cortisol
in blood does not reflect its actual concentration in cells.
• Dissecting the impact of stress on reproduction: Novel
peptide mediates the inhibitory effects of stress on
female reproduction, Tilbrook/Clarke/Hemsworth
(2009–2011).
In addition, we have shown the amount of fat on animals
affects how they respond to stress. Higher stress
responses occur in obese animals.
Australian Pork Limited Project Grant
We have shown that daylight affects milk production
in goats and sheep. As a result, we are developing
approaches to improve milk production.
We have also identified factors that affect animal welfare
and are developing recommendations to improve the
wellbeing of pigs and laying hens.
From a human perspective, we are collaborating with
researchers at the Baker IDI Heart and Diabetes Institute
and Monash Alfred Psychiatry Research Centre, exploring
the effect of stress on mental illness and metabolic
syndrome. We have shown how stress affects patients with
major depression who are taking antidepressants.
68
Professor Alan Tilbrook
• Gonadotropin inhibitory hormone, Clarke/Tilbrook
(2009–2011).
Australian Research Council Discovery Grant
Rural Industry Research and Development
Corporation Project Grant
• Improving milk yield in dairy sheep, Tilbrook/Cameron/
Dunshae/Leury (2009–2012).
• Usefulness of preference for resources and biological
functioning to assess animal welfare, Tilbrook/
Hemsworth (2010–2013).
Australian Pork Limited Project Grant
• Effects of aggressive characteristics of individual sow
and mixing strategies on the productivity and welfare of
group-housed gestating sows Hemsworth/Tilbrook
(2010–2012).
Australian Egg Corporation Limited Project Grant
• The effects of time off food and water on the welfare of
spent laying hens, Tilbrook/Hemsworth (2010–2011).
Obesity
In 2007/2008, 61% of the
Australian population were
overweight or obese.*
>> How does the brain regulate food intake,
energy use and body weight?
>> How does early-life nutrition affect weight
regulation throughout life?
>> How is fat metabolism regulated in fat
and muscle?
>> How is obesity linked to type 2 diabetes?
*Australian Bureau of Statistics 2008, National Health
Survey 2007-2008
Annual Report 2011
Obesity
Neuronal Metabolism and Degeneration
We study how the brain regulates appetite,
body weight and glucose balance during
different metabolic states and in response to
various hormones. We are interested in how
high fat or calorie restriction diets affect how
the brain regulates energy metabolism.
Research Assistants
Ms Debbie Arena
Ms Moyra Lemus
Mr Alex Reichenbach
PhD Student
Ms Dana Briggs
Honours Student
Ms Jacqueline Bayliss
We showed for the first time that the brain becomes resistant
to the effects of ghrelin, a metabolic hormone that stimulates
appetite, during diet-induced obesity. A select group of nerve
cells in the brain called NPY cells stop responding to ghrelin
so ghrelin no longer increases food intake. In the context of
obesity, we believe the brain no longer processes the basic
‘need to eat’ function, as the body has sufficient energy
stores. Excessive eating during diet-induced obesity is
most likely controlled by the rewarding properties of food
and food cravings.
Dr Zane Andrews
Metabolic Neuroendocrinology
We aim to discover novel ways of altering
energy expenditure to prevent or treat obesity.
ARC Future Fellowship
• How appetite-suppressing brain cells maintain normal
function and prevent the development of obesity
(2011–2014).
We focus on understanding how the body expends
energy. We are particularly interested in the process
of thermogenesis, a form of cellular heat production.
Awards and Achievements
Dr Andrews
• Organising chair: ESA Neuroendocrinology
Australasia symposium.
• Monash Researcher Accelerator Program.
Research Assistant
Ms Elaine Chase
PhD Students
Mr Scott Clarke
Dr Kevin Lee
Honours Students
Mr Demunu Sakda Galamulage
Mr Jared Mamrot
Our observations have significant implications for body
weight control as diet-induced weight loss would gradually
restore ghrelin’s ability to increase appetite. This makes it
difficult for most people to maintain a lower body weight
after diet-induced weight loss.
Dr Belinda Henry
Thermogenesis occurs in specialised tissues in the body
including brown fat and skeletal muscle. We have shown
that a lower rate of thermogenesis may lead to an increased
susceptibility to weight gain and obesity. We study the cellular
and molecular mechanisms that underpin thermogenesis
and hope to identify candidate targets for new anti-obesity
therapies.
NHMRC Project Grant
Do you feel hot and sleepy after lunch? Skeletal muscle heat
production increases in response to eating. This is a novel means by
which the body expends energy. The grey box illustrates meal time.
• Skeletal muscle thermogenesis in models of
predisposition to obesity, Henry/Clarke/Andrews
(2011–2013).
Awards and Achievements
Dr Henry
• Councillor, Endocrine Society of Australia.
• Program organising chair for the Endocrine Society
of Australia, Basic Science Weekend.
NHMRC Project Grants
• Our paper, published in Endocrinology, was selected
as Editor’s choice in July 2011. Henry BA et al., Central
leptin activates mitochondrial function and increases heat
production in skeletal muscle. Endocrinology, 2011.
152: 2609-2618.
• Diet-induced obesity causes ghrelin resistance, Andrews/
Spencer (2011–2013).
• Physical exercise restores energy homeostasis in obesity
through hypothalamic neurogenesis, Watt/Andrews/
Oldfield (2011–2013).
• Skeletal muscle thermogenesis in models of
predispostion to obesity, Henry/Clarke/Andrews
(2011–2013).
www.med.monash.edu.au/physiology/staff/henry.html
Ghrelin activates appetite-induced NPY brain cells (green, top panel)
and Fos protein (red, centre panel). Co-expression of Fos and NPY
neurons after ghrelin treatment (bottom panel) illustrates that ghrelin
activates NPY neurons.
• Ghrelin-induced neuroprotection is mediated by AMPK
(2009–2011).
Metabolic Neuroscience Laboratory
Professor Brian OIdfield
www.med.monash.edu.au/physiology/staff/andrews.html
Professor Michael Cowley
Director, Monash Obesity and
Diabetes Institute
Metabolic Neurophysiology
Research Fellows
Dr Pablo Enriori
Dr Maria Cecilia Garcia-Rudaz
Dr Sara Litwak
Research Assistant
Ms Joanne Pagnon
PhD Student
Ms Stephanie Simonds
Project Officer
Dr Daphne Vogiagis
Honours Students
Mr Weiyi Chen
Ms Jenny Wilson
We are mapping the pathways in the brain
that sense stored fat, stomach contents and
blood sugar. Our aim is to understand how
information is relayed throughout the brain
to balance energy intake and use, and to
control body weight.
NHMRC Project Grants
We are particularly interested in obesity, diabetes and
metabolic disease. Recently, there has been a dramatic
worldwide increase in the incidence of these conditions.
In Australia, over 13 million people are overweight or
obese and almost one million people have diabetes.
Pfizer Australia Senior Research Fellowship
Specifically, we focus on how signals from the body,
such as leptin, lose the ability to control weight once
a person becomes obese. We seek to understand how
and why the brain becomes resistant to sensing information
that would otherwise convey that the body has sufficient
stores of energy.
We have recently discovered that nerve cells in the brain
called POMC neurons detect blood sugar levels and also
regulate metabolism. In addition, we have made progress
in understanding how certain hormones regulate glucose
production and uptake, independent of insulin. We have
also applied for a patent based on these methods of
regulating blood glucose levels.
• The role of brain inflammation in leptin resistance,
Cowley (2011–2014).
• Does loss of melanocortin glucose sensing contribute
to diet induced diabetes? Cowley/Enriori/Tiganis
(2010–2013).
• Re-establishing glucose sensing in α-MSH cells to treat
diabetes, Cowley (2009–2014).
Research Fellows
Dr Juliane Kampe
Dr Aneta Stefanidis
Dr Aaron Verty
Research Assistant
Ms Erika Ortiz
PhD Students
• Does leptin cause hypertension? Cowley/Brown
(2010–2012).
Ms Elaine Adler
Ms Sarah Haas Lockie
Ms Nilanka Hertioga
Dr Cathy Jensen
(completed August 2011)
Awards and Achievements
Masters Student
Heart Research Foundation Project Grant
Professor Cowley
• Toured Australia during National Science Week.
He visited major and regional centres, where he gave
interviews and presentations about his research.
• Elected Fellow of the Australian Academy of
Technological Sciences and Engineering.
Mr Neil Forrest
This group aims to understand the role of the
brain in controlling food intake and the burning
of energy, which ultimately lead to changes in
body weight and possibly obesity.
Awards and Achievements
Recently, a number of pharmaceutical treatments have
been withdrawn because of adverse side effects, which
limits the options available to overweight or obese individuals.
Furthermore, there are no effective drugs for extreme (morbid)
obesity other than lap band and gastric bypass surgery.
Dr Aneta Stefanidis
• Recipient of a 2011 MODI travel grant.
Ms Haas Lockie
• Recipient of the inaugural Anthony Koelmeyer
International PhD Excellence award.
Our laboratory studies the mechanisms that the brain uses to
reduce hunger in certain forms of bariatric surgery and how it
curbs hunger and possibly increases energy expenditure
We hope to explain the brain mechanisms underlying the
efficacy of surgeries such as the adjustable gastric band,
which will in turn help to identify targets in the brain for antiobesity therapies.
NHMRC Fellowship
• Professor Oldfield (2006-2011).
NHMRC Project Grants
• The differential innervation of fat – potential to target
visceral adiposity, Oldfield/Clarke (2011–2013).
Neurons in the hypothalamus (green) surrounded by orexin containing
nerve fibres (red), part of the neural circuitry in the brain controlling
hunger.
• Physical activity restores energy homeostasis in obesity
through hypothalamic neurogenesis, Watt/Andrews/
Zane/Oldfield (2011–2013).
ARC Linkage Grant
• Use of an animal model to understand mechanisms
underlying reductions in body weight associated with the
use of the laparoscopic adjustable gastric band, Oldfield/
Dixon/Raven (2010–2012).
www.med.monash.edu.au/physiology/staff/oldfield.html
72
www.med.monash.edu.au/phusiology/staff/cowley.html
73
Annual Report 2011
Perinatal Programming of Stress and
Metabolism
Research Assistants
Ms Lauren Bulfin
Ms Melanie Clarke
Dr Sarah J. Spencer
We are investigating the long-term metabolic,
neuroendocrine and behavioural effects of
overfeeding during early life; the mechanisms
by which this can program obesity; and how
perinatal overfeeding can affect an individual’s
ability to combat psychological stress and
infections.
We have shown that neonatally overfed animals become
overweight during infancy and remain obese into adulthood.
We have also seen that these neonatally overfed animals
have exaggerated responses to psychological stress and to
an immune challenge. Our research helps explain how early
life overfeeding can program these responses. Our work has
important health implications for obese individuals trying to
overcome stress and improve immune responses.
The early life environment is crucial in establishing an animal’s
long-term physiology. As such, over- or under-nutrition
in infancy can significantly affect the ability to regulate
metabolism and body weight throughout life.
NHMRC Peter Doherty Postdoctoral Fellowship
We are therefore investigating:
• How early life nutrition programs the brain to regulate
weight; and
• What are the long-term metabolic, neuroendocrine, and
behavioural effects of early nutrition on the stress and
immune systems?
• Neuroendocrine mechanisms for stress
hyporesponsiveness in lactating females (2007-2011).
NHMRC Project Grant
• Diet-induced obesity causes ghrelin resistance, Andrews/
Spencer (2011-2013).
Australia Research Council Discovery Project Grant
• Early life overfeeding: Mechanisms for programming
obesity and long-term immune dysfunction (2010-2012).
Monash Research Accelerator Program Award
• (2011–2012)
www.med.monash.edu.au/physiology/staff/spencer.html
Biology of Lipid Metabolism
This group is working to develop preventative
strategies to overcome obesity, while also
investigating the link between obesity and
type 2 diabetes.
Postdoctoral Fellows
Dr Andrew Hoy
Dr Ruth Meex
Dr Romana Stark
Research Assistants
Ms Emma Brunton
Ms Maria Matzaris
Ms Joanne Pagnon
PhD Students
Mr James Boon
Ms Melissa Borg
Ms Vanessa Haynes
Ms Rachael Mason
Honours Student
Ms Alice Barnett
Associate Professor Matthew Watt
Monash Fellowship
• Arresting the obesity epidemic: Molecular and cell
biology of lipid metabolism in chronic metabolic
disease, Watt (2008–2012).
Obesity is a serious medical condition that has doubled in
prevalence over the past 20 years, and affects one in every
three Australian adults. We study the molecular and cellular
regulation of fat metabolism in fat and skeletal muscle, and
how defects in fat metabolism lead to insulin resistance,
a precursor to type 2 diabetes. We aim to influence the
development of preventative and therapeutic strategies
for obesity and related disorders.
NHMRC Senior Research Fellowship
• Associate Professor Watt (2010-2014).
NMHRC Project Grants
• Physical activity restores energy homeostasis in
obesity through hypothalamic, Watt/Andrews/Oldfield
(2011–2013).
• Regulation of insulin sensitivity by reactive oxygen
species, Tiganis/Watt (2010–2012).
• Identifying a novel role for pigment epithelium-derived
factor in obesity-related metabolic dysfunction, Watt
(2010–2012).
• Circulating ceramides, inflammation and insulin
resistance, Watt (2009–2011).
Image showing lipid droplets containing fat (red) in an adipocyte
(fat cell). The protein adipose triglyceride lipase (green), which breaks
down fat is also shown. Image: Joanne Pagnon.
ARC Discovery Project Grant
• Regulation of lipolysis: New players, new paradigms
(2009-2011).
www.med.monash.edu.au/physiology/research/bolm.html
74
Structural Biology
Understanding the molecular
basis of biology and disease
>> Infection
>> Immunity
>> Malaria
>> Anti-cancer agents
>> Alzheimer’s disease
>> Huntington’s disease
>> Cardiovascular disease
>> HIV
>> Virus biology
>> Toxin biology
>> Developmental biology
>> RNA biology
>> Bioinformatics
Structural biology also plays
a central role in the design of
therapeutic drugs and novel
vaccines, and tools for
biomedical applications.
A molecular model of a non-fluorescent GFP-like protein isolated from a marine
coral. This cut-away representation of the 11 stranded ß–barrel reveals the
protected light absorbing chromophore, with water molecules (green spheres)
and surfaces (mesh). Image: Jion Battad.
Annual Report 2011
Structural Biology
Pepidomimetic Drug Design and
Membrane Nanotechnology
Our group focuses on peptide-based drug
design and biomembrane nanotechnology.
Research Fellows
Dr Mark Del Borgo
Dr John Lee
Research Assistant
Ms Sharon Unabia
PhD Students
Ms Romila Devi-Gopalan
Ms Ann Du
Mr Daniel Hirst
Mr John Paul Juliano
Ms Jia Li Zhai
In collaboration with Professor Patrick Perlmutter (School
of Chemistry), we are developing novel compounds that
allow us to exploit the potential of peptides as drugs. We
are currently applying our technology to develop cancer
vaccines (with Associate Professor Tony Purcell, University
of Melbourne), new treatments for cardiovascular disease
(with Professor Rob Widdop and Dr Emma Jones,
Department of Pharmacology) and inhibitors of HIV
budding (with Dr Miranda Shehu-Xhilaga and Associate
Professor Gilda Tachedjian, Burnet Institute).
Viral Immune Evasion Laboratory
Professor Mibel Aguilar
Associate Dean (Research Degrees)
ARC Discovery Grant
• The mechanism of membrane disruption by antimicrobial
peptides, Aguilar/Separovic/Mark (2011–2013).
• The design and synthesis of inhibitors of HIV budding,
Aguilar/Shehu-Xhilaga, (2010–2012).
National Heart Foundation
• PIPS regulate G protein-coupled receptors,
Aguilar/Thomas (2011-2012).
Mason Foundation
Research Assistant
• Identification of new drugs to treat Alzheimer's disease,
Aguilar/Small/Perlmutter (2011).
PhD Student
Mr Luke Cossins
Ms Leigh Yang
Our membrane nanotechnology projects include: new
methods for membrane protein purification and analysis
for Alzheimer’s disease (with Professor David Small,
Menzies Research Institute), G protein-coupled receptor
function (with Professor Wally Thomas, University of
Queensland), antimicrobial peptide function (with Professor
Frances Separovic, University of Melbourne) and new
biosensor devices (with Farfield Scientific).
Dr Natalie Borg
We study the role of proteins involved in
viral immunity and evasion to understand
viral disease.
ARC Discovery Project Grant
Our protein targets come from a growing family of
enzymes that regulate almost all cellular processes.
The enzymes, called E3 ligases, literally add molecular
tags to other proteins, modifying the tagged protein’s
function. Viruses can use these mechanisms to their
advantage to manipulate the immune system and
avoid detection.
• (2008–2011)
Our ultimate aim is to decipher the role of these proteins
in the cell. This information could be exploited to design
novel treatments to enhance immunity against persistent
or virulent infections such as influenza, and to design
anti-viral therapeutics. As these proteins are too small
to see with a microscope, we use X-ray crystallography,
biophysical approaches and cellular assays to gain
information about the molecular shape and function
of these molecules and their binding partners.
• (2011–2013)
NHMRC Career Development Award
A molecular tag that is added to target proteins to modify their function.
www.med.monash.edu.au/biochem/staff/borg.html
NHMRC Project Grants
• Elucidating the mechanism of action of dendrimer
nanoparticles against HIV, Tachedjian/Gorry/Ramslund/
Aguilar (2011–2013).
• The receptor-associated protein (RAP) as a molecular
chaperone for the amyloid protein (Abeta) of Alzheimer's
disease, Small/Aguilar/Shepherd/Strickland (2010–2012).
• The role of transthyretin in familial amyloidotic
polyneuropathy, Small/Parkington/Chung/Aguilar/
Coleman (2009–2011).
Protein Misfolding Laboratory
Schematic showing how the structure of a biological membrane can
be studied by a new type of biosensor that measures the changes in
packing, alignment and degree of order of lipid molecules assembled
in the bilayer.
www.med.monash.edu.au/biochem/research/projects/peptide.html
Research Fellows
Structural Microbiology
Research Fellows
Dr Natasha Ng
Dr Andrew Sivakumaran
Dr Trifina Sofian
Research Assistant
Ms Sally Troy
PhD Student
Mr Adam Shahine
Honours Student
Ms Li Lynn Tan
Associate Professor Travis Beddoe
Dr Victoria Hughes
Dr Mary Pearce
Dr Noelene Quinsey
Dr Amy Robertson
We study virulence factors from pathogenic
microbes using X-ray crystallography.
Pfizer Australia Research Fellowship
Pathogenic bacteria use surface and secreted proteins to
cause infection and/or evade the immune system. These
proteins have varied functions: they stick to cells, produce
toxins and manipulate both host immune responses and
cellular function.
Awards and Achievements
Ms Weiwen Dai
Mr Nik Sotirellis
Dr Travis Beddoe
• Finalist, Eureka Prize for Infectious Diseases Research.
PhD Students
• (2010–2014)
We use a combination of biochemistry, biophysical and X-ray
crystallography approaches to determine the molecular role
of these infectious proteins. This will not only unravel key
aspects of microbial pathology, but will also provide a range
of novel antimicrobial drug targets.
Research Assistants
Ms SHani Keleher
Ms Anja Knaupp
Ms Miranda Wills
Ms Li Yang
Ms Evelyn Yip
Masters Student
Mr Christopher Lupton
Honours Students
Mr Joybrata Banerjee
Mr Jeremy Nagel
In future studies, we will scour bacterial genomic databases
for unknown proteins that may play a role in bacterial
physiology and pathogenesis.
Professor Stephen Bottomley
We study how proteins fold to their correct
shape, what happens when this goes wrong
and develop therapeutic approaches for
a range of devastating diseases such as
Huntington’s disease and emphysema.
NHMRC Project Grant
For a protein to function it has to fold into its correct shape.
However, this reaction is complex and can go wrong. A large
number of disorders, including Alzheimer’s and Huntington’s
diseases are caused by a failure of a specific protein to fold
correctly. We use a range of technologies, including protein
engineering, biological spectroscopy, structural biology and
cellular approaches to understand how proteins fold and
misfold.
• Analysing the detrimental effects of polyglutamine
expansion, Bottomley/Devlin (2010–2012).
• To investigate how the aggregation of proteins during
neuronal injury promotes neurotoxic plasmin formation,
Medcalf/Bottomley/Samson (2010–2012).
ARC Discovery Grant
From our research studies, we have characterised proteins
which bind to and stabilise misfolding proteins. Specifically,
we identified a cellular chaperone molecule that binds to
ataxin-3 and prevents its misfolding. Aggregation of ataxin-3
causes Machado Joseph disease, a neurodegenerative
disorder which affects indigenous Australians in the Northern
Territory. We are exploring treatment approaches for this
disease.
NHMRC Senior Research Fellowship
• Stephen Bottomley (2007–2011).
NHMRC Program Grant
• Control of proteases in infectious, degenerative and
cardiovascular disease, Whisstock/Bird/Buckle/
Bottomley/Pike/Smith (2008–2012).
We discovered that the interaction between Ataxin-3 and the chaperone
αB-crystallin prevents ataxin-3 aggregation. We then used Nuclear
Magnetic Resonance to identify which regions of Ataxin-3 (coloured)
interact with αB-crystallin.
NHMRC Project Grants
• Structure and functional characterisation of AB5 toxins
(2011–2013).
www.med.monash.edu.au/biochem/staff/bottomley.html
• Cytokine structure and mechanisms of a superagonist
antibody (2011–2013).
ARC Discovery Grant
• Evolution of AB5 toxins (2010–2012).
The crystal structure of a bacterial virulence factor with its bound
substrate. (Vivian et al., Structure, 2010).
www.med.monash.edu/biochem/staff/beddoe.html
78
79
Annual Report 2011
Structural Biology
Protein Structure, Dynamics and Bioinformatics
Research Fellows
Dr David Hoke
Dr Itamar Kass
Dr Grischa Meyer
Software Developers/
Bioinformaticians
Mr Steve Androulakis
Mr Mark Bate
PhD Students
Mr Daniel Andrews
(with Dr Anna Roujeinikova)
Mr Yasir Arafat
Ms Olga Ilyichova
Ms Bindu Jayakrishnan
Dr Fasséli Coulibaly
NHMRC Career Development Award
• (2007–2011)
We study the infectious cycle of viruses at a
molecular level to understand their assembly,
evolution and virulence.
NHMRC Program Grant
We work on the following projects:
• Control of proteases in infectious, degenerative and
cardiovascular disease (2008–2012).
Structural analysis of early steps in poxvirus assembly
• Understanding the assembly of poxvirus particles
(2010–2012).
We aim to understand how the structure and
dynamics of proteins dictates their function.
NHMRC Senior Research Fellowship
Currently, we study the role of proteases in human health
and disease. We use a combination of crystallography and
computational techniques to design inhibitors of human
Kallikrein-4, human aminopeptidases, and active/inactive
proteases from the scabies mite.
We also use X-ray crystallography, Surface Plasmon
Resonance Imaging and biochemical techniques to study
the interaction between the Type 1 diabetes autoantigen
Glutamic Acid Decarboxylase (GAD65) and autoantibodies.
Research Fellows
Dr Marcel Hijnen
Dr John Martyn
Research Assistant
In collaboration with the Monash eResearch Centre and the
Australian Synchrotron, we use X-ray crystallography and
computer science approaches to create new tools for protein
structure determination. Recently, we developed a new online
data management program called TARDIS, the world’s first
repository for raw X-ray diffraction data. We also develop and
host a range of bioinformatics resources.
Using molecular dynamics simulations, we aim to understand
the role of conformational change and flexibility in protein
function. We require high performance supercomputers for
this task, and use the Monash Sun Grid and Orchard, an
800-core Apple supercomputing cluster at Monash, as well
as the Victorian Life Sciences Computation Initiative.
We collaborate with scientists university-wide, nationally and
internationally.
Ms Cathy Accurso
PhD Student
Ms Suzan Cingi
Poxviruses are among the largest viruses infecting humans
and have a complex assembly involving multiple steps of
maturation. We generate 3-dimensional crystal structures
of key proteins to investigate the molecular details of these
assembly processes.
• Structural analysis of poxvirus assembly (2009–2012).
NHMRC Project Grants
• Structure and function of the HCV glycoproteins
(2010–2012).
ARC Discovery Project Grant
• Microcrystallography of spheroids: crystalline armours of
insect viruses (2010-2012).
Microcrystallography
CASS Foundation
We use X-ray microcrystallography to analyse tiny viruscontaining crystals, which are produced by insect viruses.
These crystals function as armours for virus particles so that
viruses can survive for decades in the environment.
• Micro Cubes as a vaccine against HIV (2011).
Novel vaccine delivery approaches
Crystals formed in vivo by insect viruses have remarkable
robustness and packaging ability. We are interested in
exploiting these features to engineer microparticles as a
potential HIV vaccine candidate.
Bill and Melinda Gates Foundation, Grand Challenges
Explorations Grant
• Micro Cubes as a vaccine for the developing world
(2011-2012).
Awards and Achievements
Dr Coulibaly
• Accepted into Monash Research Accelerator program
(2010–2011).
Conformational flexibility of a peptide (blue) bound to the Major
Histocompatibility Complex revealed by Molecular Dynamics simulations
taken every 10 nanoseconds. The peptide conformation in the crystal
structure is shown in yellow.
Structure of the three classes of viral crystalline armours produced by RNA and DNA viruses.
www.med.monash.edu.au/biochem/staff/abuckle.html
Structural Immunology
Structural Virology
Associate Professor Ashley Buckle
Dr Craig Clements
www.med.monash.edu.au/biochem/staff/coulibaly.html
We investigate the interaction between
molecules of the immune system.
The innate immune system is the first line of defence
against invading pathogens. Receptors on immune cells
called Natural Killer cells can distinguish between ‘self’ and
‘non-self’ molecules presented by the body. This ability to
identify cells containing ‘non-self’ material ultimately leads to
the destruction of infected cells, and also plays a role in the
body’s response to cancerous cells.
Research Assistant
Ms Maya Olshina
PhD Students
Mr Nicholas Walpole
Mr Li Zeng
We use a combination of structural biology and biophysical
techniques to determine what features are important for the
Natural Killer cell to ‘see’ an infected cell. We gain a greater
understanding of the immune response to infection and
cancer, which may help in the design of better therapeutics.
ARC Discovery Project Grant, including
Queen Elizabeth II Fellowship
• Investigation of the fundamental roles of class Ib MHC
molecules in immunity (2007-2011).
80
Comparison of the binding of three different peptides to HLA-G.
(Walpole et al., Journal of Molecular Biology, 2010. 397: 467-480).
81
Annual Report 2011
Structural Biology
Toxin Biology Laboratory
Dr Michelle Dunstone
Fluorescent Proteins and their Applications
We study the function of toxins used by
pathogens and the human immune system.
We study the properties of GFP-like proteins
and develop novel optical tools for biomedical
applications.
Pore forming toxins are proteins commonly identified as
bacterial virulence factors, proteins of the immune system
and animal venoms. These molecules are able to change
shape from water soluble single proteins to lipid membrane
inserted rings. These rings act as holes in the target cell
membrane that can result in cell death by forming holes in
the cell or by allowing other toxins to invade.
Research Fellow
NHMRC Career Development Award
Research Assistants
• The role of Membrane Attack Complex/Perforin-like pore
forming proteins in disease and immunity (2010–2014).
Dr Tamas Hatfaludi
Ms Bethany Crane
Ms Sue Ekkel
PhD Student
Ms Stephanie Kondos
CASS Foundation Science and Medicine Grant
Mr Jion Battad
Mr Alexander May
Mr Craig Don Paul
Naturally occurring and engineered members of the GFPsuperfamily collectively have an extraordinary range of
properties. In particular we are interested in how the structure
of these proteins gives rise to their optical properties. We
use this knowledge to design and engineer new proteins and
biosensors for investigating the organisation of molecular
networks in living cells. In addition to fluorescent probes for
monitoring events in live cells, we also develop optogenetic
tools that when illuminated allow the control of specific
cellular pathways.
Honours Student
NHMRC Program Grant
Research Assistant
• Intracellular survival of Burkholderia pseudomallei
and evasion of autophagy, Boyce/Devenish/Prescott
(2009–2012).
PhD Students
ARC Discovery Project
• Structural and functional studies on Membrane Attack
Complex/Perforin-like proteins (2009–2011).
Dr Mark Prescott
Ms Giuseppe Lucarelli
Model of a MACPF pore in a cell membrane. Modelled by Dr Michael
Kuiper, Victorian partnership for advanced computing.
• Structural characterisation of a novel and potent
anti-inflammatory protein (2011).
Ms Julia McCoy
A molecular model of a non-fluorescent GFP-like protein isolated
from a marine coral. This cut-away representation of the 11 stranded
ß–barrel reveals the protected light absorbing chromophore, with water
molecules (green spheres) and surfaces (mesh). Image: Jion Battad.
Monash Research Accelerator Program
• The study of MACPF pore structure and their function
in bacteria (2011–2012).
www.med.monash.edu.au/biochem/staff/prescott.html
www.med.monash.edu.au/biochem/staff/dunstone.html
Macromolecular Structure and Interactions
in Cellular Function
Structural Biology of Proteases and their
Inhibitors
We study the molecular basis of
macromolecular interactions that occur in
human cells: gene expression, cell growth and
proliferation, and cellular immunity.
Dr Sheena McGowan
We are particularly interested in protein-oligonucleotide
systems. These include proteins which bind to mRNA to
regulate translation and proteins that recognise viral RNA
and initiate immune responses to viral infections. We also
design and test new antibiotics against bacterial pathogens
and peptide-based inhibitors of cancer cell proliferation and
migration.
We characterise novel malarial drug targets
and use this knowledge to design new
anti-malarial therapies.
Research Assistants
Ms Kitmun Huynh
Ms Komagal Sivaraman
Due to the rapid spread of drug resistance in the malaria
parasite there is an urgent need for new treatment options.
The action of two neutral metalloaminopeptidases, M1
alanyl aminopeptidase and M17 leucyl aminopeptidase,
are essential to the parasite's growth and development.
Blocking the activity of these molecules is an effective
disease prevention strategy. We use techniques in X-ray
crystallography, biochemistry and biophysics to characterise
these enzymes. This information is then used to develop
compounds with potential applications in human medicine.
NHMRC Senior Research Fellowship
• Professor Wilce, Protein-RNA interactions (2007-2011).
Associate Professor Jackie Wilce
Professor Matthew Wilce
NHMRC Project Grants
• Characterisation of the growth receptor bound 7 (Grb7)
protein and protein and RNA partners involved in the
regulation of stress granule formation and cell migration
(2011-2013).
• Protein recognition of small RNAs in innate immunity
(2011-2013).
• Structural and functional role of HIV-1 gp41 terminal
interactions in the membrane fusion mechanism
(2009-2011).
ARC Discovery Grants
• Specificity and architecture of protein-mRNA interactions
regulating gene expression (2011-2013).
• Optimisation of peptidic non-phosphorylated inhibitors of
the Grb7 SH2 domain (2009-2011).
NHMRC Project Grant
• Plasmodium falciparum neutral aminopeptidases:
Structure-function analysis for the discovery of
anti-malarial drugs (2009–2011).
Research Fellows
ARC Future Fellowship
• (2010–2014)
Monash Research Accelerator Program
• (2011–2012)
The X-ray crystal structure of the Plasmodium falciparum M17
aminopeptidase (McGowan et al., Proceedings of the National
Academy of Sciences, USA, 2010. 107(6): 2449-2454).
Dr Simone Beckman
Dr Menachem Gunzburg
Dr Zhihe Kuang
Dr Reece Lim
Dr Nicole Pendini
PhD Students
www.med.monash.edu.au/biochem/staff/mcgowan.html
Mr Nigus Ambaye
Mr Chris Szeto
Ms MinYin Yap
Masters Student
Crystal structure reveals the binding mode of a peptide inhibitor of Grb7 that is involved in cancer cell migration and proliferation.
Mr Yano Yoga
http://research.med.monash.edu.au/wilce
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Annual Report 2011
Structural Biology
Protein Crystallography Unit
Professor Jamie Rossjohn
We study molecular interactions central
to infection and immunity. The group uses
structural biology, including synchrotron
radiation, and biophysical approaches as
the main research tools.
Awards and Achievements
• Awarded Roche Organ Transplantation Research
Foundation Recognition Prize jointly with Professor
McCluskey.
Ms Margaret Bills
Dr Jennifer Huynh
Our research allows us to understand host recognition
and pathogen responses. We collaborate with scientists
throughout Australia and internationally and are supported
by funding from the ARC, NHMRC, Anti-Cancer Council,
NIH and Monash University. The laboratory is also an
integral part of the ARC Centre of Excellence in
Structural and Functional Microbial Genomics.
Research Fellows
NHMRC Project Grant
• Mallevaey et al., A molecular basis for NKT cell
autoreactivity and recognition of CD1d-self antigen.
Immunity, 2011. 34: 315-326.
• A structural investigation into the adaptive immune
response to a persistent and ubiquitous human virus,
Rossjohn/Purcell (2011–2013).
• Wun et al., A molecular basis for the exquisite CD1drestricted Ag-specificity and functional responses of NKT
cells. Immunity, 2011. 34: 327-339.
NHMRC Program Grant
• Uldrich et al., A semi-invariant Vα10(+) T cell antigen
receptor defines a population of natural killer T cells with
distinct glycolipid antigen-recognition properties. Nat
Immunology, 2011. 12: 616-23.
Administration
Dr Sara Baratchi
Dr Richard Berry
Dr Mugdha Bhati
Ms Renee Duncan
Dr Stephanie Gras
Dr Dene Littler
Dr Thao Nguyen
Dr Jerome Le Nours
Dr Onisha Patel
Dr Jan Petersen
Dr Hugh Reid
Dr Alex Theodossis
Dr Kelly-Anne Twist
Dr Julian Vivian
Dr Neal Williams
Dr Pascal Wilmann
Research Assistants
Mr Andrew Gibb
Mr Ray Koh
Ms Kylie Loh
Ms Halim Noor
Ms Maria Sandoval
Ms Christina Wang
PhD Students
Mr Andrew Clarke
Mr John Liu
Ms Melissa McKnight
Mr Stephen Scally
Mr Adam Shahine
Mr Nick Walpole
Mr Li Zeng
Honours Student
Ms Amelia Aslanides
Mr Simon Giang
Ms Sofia Mahood-Ul-Hassen
Ms Li Lynn Tan
• Antigen presentation, recognition and the immune
response, McCluskey/Heath/Carbone/Brooks/Rossjohn/
Shortman (2007v2011 and 2012–2016).
NHMRC Australia Fellow
• Australian Fellowship, Rossjohn (2011–2016).
ARC Federation Fellow
• An investigation into Infection, Immunity and Rational
Drug Design, Rossjohn (2006–2011).
ARC Discovery Grants
• A structural and functional investigation into events within
the immunological synapse, Rossjohn/McCluskey
(2011–2013).
• A structural investigation into the peptide loading
complex molecular machine, Rossjohn (2008–2012).
Infection, Immunology and
Developmental Biology
Professor Rossjohn
• Finalist, Eureka Prize for Infectious Diseases Research,
jointly with Associate Professor Beddoe and Professor
Paton.
• Top ranked 2011 NHMRC program grant.
• Awarded NHMRC Australia Fellowship.
• Pellicci et al., Recognition of β-linked self glycolipids
mediated by natural killer T cell antigen receptors. Nature
Immunology, 2011. Jul 31; 12(9):827-833.
• Vivian et al., Killer Immunoglobulin Receptor 3DL1mediated recognition of Human Leukocyte Antigen B.
Nature, 2011. Oct 23: doi: 10.1038/nature10517. [Epub
ahead of print].
Mr Andrew Clarke
• Recipient of the inaugural Anthony Koelmeyer
International PhD Excellence award.
Research Fellows
Dr Tamas Hatfaludi
Dr Anabel Herr
Dr Hilary Hoare
Dr Travis Johnson
Dr Ruby Law
Dr Isabelle Lucet
Dr Siew Siew Pang
Dr Andrew Perry
Dr Corrine Porter
Dr Carlos Rosado
Dr Jiangning Song
Dr Dr Daouda Traore
Dr Mark Walter
Research Assistants
Ms Gilu Abraham
(with Dr Lucet)
Ms Rebecca Bamert
(with Dr Lucet)
Mrs Tanya BashtannykPuhalovich
Ms Devadharshini Jeevarajah
Mr Gordon Lloyd
Mr Adam Quek (with Dr Law)
Ms Qingwei Zhang
PhD Students
Ms Michelle Bennett
Ms Susie Berkowicz
Ms Tova Crossman
Ms Aminah Giousoh
Mr Trevor Key
Ms Stephanie Kondos
Mr Chris Langendorf
Mr Khalid Mahmood
Mr Cyril Reboul
ARC Centre of Excellence
• Structural and functional genomics, Adler/Rood/Coppel/
Davies/Rossjohn/Whisstock/Nagley/Devenish/ Hertzog/
Meussen/Smith (2006–2013).
ARC LIEF Grant
• An advanced flow cytometry facility for the Peter Doherty
Institute, Carbone/Heath/Kent/Purcell/Rossjohn/Godfrey
(2011).
Professor James Whisstock
We focus on understanding the structure,
function and biology of proteins involved
in infection, cancer immunology and
developmental biology.
ARC Centre of Excellence in Structural and Functional
Microbial Genomics
We are particularly interested in how pore forming
Membrane Attack Complex/Perforin-like (MACPF) proteins
eliminate virally infected and pre-cancerous cells. We
also study the role of cholesterol dependent cytolysins
in infection. Finally, we are interested in how certain
MACPF proteins function in developmental processes and
neurobiology, for example in terminal patterning in the fruit
fly and in brain development in mammals.
• Development of a novel small molecule treatment
for cerebral malaria through inhibition of perforin
(2010–2011).
• (2010–2013)
Wellcome Trust Seeding Drug Discovery Interim Award
From a protease perspective, we are using structural and
biochemical approaches to understand how proteases and
protease inhibitors influence blood coagulation, fibrinolysis
and tissue remodelling. Recent successes include
understanding how plasma antiplasmin interacts with and
inhibits the fibrinolytic enzyme plasmin.
In collaboration with Dr Isabelle Lucet, Professor Andrew
Wilks and Professor Bill Charman, we are studying the
structure, function and biology of Plasmodium falciparum
kinases, which play a fundamental role in malaria
pathogenesis.
NHMRC Project Grant
• Structural and functional studies on perforin (2010–2013).
NHMRC Program Grant
• Protease systems biology (2010–2012).
ARC Federation Fellowship
• Membrane attack complex proteins in defence, attack
and developmental biology (2010–2012).
ARC Discovery Project Grant
The X-ray crystal structure of perforin (Law et al., Nature, 2010)
together with perforin crystals (background). Perforin eliminates virally
infected and pre-cancerous cells; elevated perforin activity is associated
with a range of immune driven diseases. Structural studies on perforin
will allow further development of the treatment of perforin related
immune diseases.
• Structural and functional studies on MACPF proteins
(2010–2011).
ARC Super Science Fellowship
• Pore forming proteins as delivery devices (2010–2012).
http://research.med.monash.edu.au/whisstock/
ARC Linkage Grant
• Exploring therapeutic approaches to combat celiac
disease, Rossjohn/Anderson (2011–2013).
ARC Super Science Fellowship
• Design and fabrication of molecular machines: The
nanomachines of the future, Lithgow/Rossjohn/Martin/
Strugnell (2011–2013).
Anti-Cancer Council
Crystal structure of Valpha10-Vbeta8.1 NKT TCR in complex with
CD1d-alphaglucosylceramide (PDB ID: 3RUG). (Uldrich et al., Nature
Immunology, 2011. 12: 616-623).
• A structural and functional investigation into tumour
rejection by NKT cells, Rossjohn/McCluskey (2010–2012).
NIH RO1
• Characterisation of a novel AB5 cytotoxin, Paton/Paton/
Rossjohn (2007–2011).
http://research.med.monash.edu.au/rossjohn/index.php
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Facilities and Centres
Facilities and
Centres
Facilities
Australian Phenomics Network
>> Australian Phenomics Network
Lead Scientist:
Associate Professor Moira O’Bryan
Node Manager: Dr Leanne Cotton
>> Macromolecular Crystallisation Facility
(The Grollo Ruzzene Foundation Centre
for Protein Structure)
The Australian Phenomics Network
(APN) provides Australian researchers
with services for the creation, characterisation and
cryopreservation of mouse models of human disease.
>> Micromon
Established in 2007, the multiple partnering institutions of the
APN receive generous funding from the Australian Government's
National Collaborative Research Infrastructure Strategy and
Education Investment Fund, with additional funds from the
National Health and Medical Research Council, state
governments and research institutions, providing Australian
researchers access to APN support at substantially
subsidised costs.
>> Monash Antibody Technologies Facility
>> Monash Biomedical Proteomics Facility
>> Monash Micro Imaging
>> Protein Production Unit
>> ARC Centre of Excellence In Structural
and Functional Microbial Genomics
>> Monash Comprehensive Cancer
Consortium
>> Monash Obesity and Diabetes Institute
•• The Monash node of the Australian Phenome Bank (APB)
is a repository of genetically modified mouse strains. The
APB has established an archive consisting of cryopreserved
mouse sperm and embryos, maintaining a centralised
database detailing mouse strains stored in Australia as
live or cryopreserved material. Scientists are encouraged
to contribute new strains to this archive and/or search
the database for mouse models of interest. Depositing
researchers maintain ownership of the strain and can
nominate availability to other scientists.
Two Monash services are proud partners of the APN:
•• The Monash Embryonic Stem (ES) Cell to Mouse service
is a core APN facility which provides ready access to the
global initiative to systematically inactivate every gene in
the mouse genome and generate research models for all
20,000+ genes. Australian researchers choose the genetically
modified ES cell line(s) of interest and lodge a request, while
the service does the rest - delivering heterozygous genetically
modified mice to their facility to advance their research.
Microinjection of ES cells.
www.australianphenomics.org.au/
Macromolecular Cystallisation Facility
(The Grollo Ruzzene Foundation Centre for Protein Structure)
Director: Associate Professor Matthew Wilce
Manager: Dr Danuta Maksel
Support: Dr Robyn Gray
The Facility, which is the largest of its kind worldwide, was
supported by funds from the Australian Research Council (LIEF),
Monash University, Australian Regenerative Medicine Institute
and the Grollo Family Foundation.
Crystallography can help explain the structure and function
of large molecules such as proteins, and is a valuable tool
for drug design. A bottle neck to structural studies has been
the production of crystals. The Crystal Palace, housed in
building 16 at the Monash Clayton campus, is an automated
macromolecular crystallisation facility that overcomes this
bottleneck. A robot can quickly and reproducibly screen
thousands of samples for the growth of crystals, work with
minimal volumes, provide regular updates of these experiments
via a web-based interface and integrate data through an Oracle
database.
The Rigaku Crystalmation robot can set up a crystallisation tray
of 96 trials, aliquotting as little as 50 nL of sample per trial in
approximately 7 minutes, and can store data for about 5000
96 well trays. Individual crystals are harvested and diffraction
data is collected from either one of the two in-house X-ray
diffractometers in building 76, or off-campus at the Australian
Synchrotron Macromolecular Beamlines, in Clayton.
Watching crystals grow using the Crystalmation Web-viewer.
Crystalmation robotic system at Macromolecular Crystallisation Facility.
www.monash.edu.au/research/infrastructure/platforms/crystallisation.html
87
Annual Report 2011
Facilities and Centres
Micromon
Monash Biomedical Proteomics Facility
Manager: Mr Mark Cauchi
Director: Professor Ian Smith
Micromon specialises in providing premium quality DNA
technology services to Monash researchers across all
campuses, as well as external customers throughout Australia.
Our premier service continues to be long-read DNA sequencing,
where we provide researchers with high-quality DNA sequencing
data and outstanding client support.
Mass spectrometry has now become the leading tool for protein
identification, quantification and sequencing. With generous
funding from the Victorian State Government, NCRIS and the
ARC Centre of Excellence in Structural and Functional Microbial
Genetics, the Monash Biomedical Proteomics facility can offer
proteomics services including: qualitative and quantitative mass
spectrometry; HPLC; N-terminal sequencing; 1D and 2D
SDS-PAGE.
The Next-generation sequencing facility, which operates an
Illumina GAIIx genetic analyzer, produces high quality genomic
data that has been successfully used in various research
projects, resulting in publications during the past year. This
service, run by Scott Coutts, is currently being accredited with
the Illumina CSPro certification for guaranteed quality delivery.
Our facility is partially supported by the National Collaborative
Infrastructure Scheme initiative which has been used to
establish Bioplatforms Australia, incorporating Proteomics
Australia. This organisation, which groups together technical
facilities, enables Australian scientists to access high-end
technologies at subsidised costs. The Monash Biomedical
Proteomics Facility operates as the Victorian node of Proteomics
Australia, with other sites in New South Wales, Queensland and
South Australia.
Micromon also offers services in oligonucelotide synthesis,
microbial testing, and media and culture supply.
The Recombinant DNA Technology workshop that is run
each November was again fully booked. Aside from providing
participants from around the country with training in the
essential skills of molecular biology, the course provides
teaching opportunities for lecturers and graduate students from
the School of Biomedical Sciences.
Applied Biosystems 3730 Genetic Analyzer
In 2011, the facility provided proteomics services for research
clients at Monash University, Victorian and Queensland
institutes, and commercial companies from Victoria and Western
Australia. The facility is also a member of the Victorian Platform
Technologies Network.
www.micromon.monash.org
Our facility is operated by Dr David Steer, Ms Shane Reeve and
Ms Josie Lawrence under the direction of Professor Ian Smith.
Monash Antibody Technologies Facility
www.med.monash.edu/biochem/facilties/proteomics
Sample being loaded for protein sequencing.
Director: Professor Edouard Nice
Monoclonal antibodies are biological molecules that are used to
detect, isolate, quantify and characterise proteins, and represent
the fastest growing class of therapeutics. The monoclonal
antibody market is one of the most lucrative and high growth
sectors of the health biotechnology area and is estimated to be
worth more than US $49 billion by 2013.
Monash Micro Imaging
Director: Associate Professor Ian Harper
Monash Micro Imaging, the University core facility
for microscopy in the life sciences, has continued
to grow and expand its imaging research support
in 2011. The Facility now reports to the Faculty of
Medicine, Nursing and Health Sciences and the
Research and Research Infrastructure Office. The
School of Biomedical Sciences continues to provide a significant
demand for analytical imaging, and as a result, MMI has further
expanded its capacity and training.
The Monash Antibody Technologies Facility (MATF) addresses
an important need in the market for customised high affinity
antibodies. Since January 2009 MATF has produced over
1000 antibodies for more than 175 clients. MATF customers
represented all areas of the research community: 47% Monash
University, 21% Australian academic, 17% Australian industry,
7.5% international academic and 7.5% international commercial.
Recent operational changes to the facility have brought about
improvements to key processes such as sample quality control,
customer service, finance and project management. In response
to our customers’ requests, MATF has provided additional
services, including: antibody purification, comprehensive
characterisation and development of alternative screening tools,
SPR analysis and ELISA development.
www.matf.monash.org
The Facility continues to provide extensive imaging access
across the University, with over 320 registered users, of whom
210 were trainees in new techniques or new instrumentation. In
addition MMI ran 10 training workshops and short courses, and
13 PhD’s were completed using MMI instrumentation. These
activities are reflected in an increasing number of publications
each year, and many of the images in this annual report have
been produced on MMI instruments.
Research highlights include the strengthening of advanced
imaging capacity, upgrading one of the optical workstations
to confocal capacity (Nikon C1), converting a Leica SP5
inverted multiphoton microscope to an upright configuration to
facilitate small animal imaging for Developmental Biology and
Regenerative Medicine researchers, and the establishment of a
cryo-preparations laboratory for the MMI BioEM Facility.
Robotic workstations at MATF.
In addition, in August a Zeiss 780 confocal/multiphoton
microscope with FCS (funded by Australian Regenerative
Medicine Institute) was installed in the Advanced Optical
Imaging Facility (Clayton) for studies of mouse embryo
development, with resolution capabilities from cellular
structure to single molecule detection.
ARMI and MMI staff celebrating the installation of the new Zeiss LSM780 confocal/
multiphoton microscope in August 2011. Present, from left to right: Juan Silva (ARMI),
Stephen Firth (MMI), Professor Nadia Rosenthal (Director, ARMI), Associate Professor Ian
Harper (Director, MMI), Gurpreet Kaur and Dr Nico Plachta (Group Leader, ARMI).
www.microimaging.monash.org
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Annual Report 2011
Protein Production Unit
Scientific Director: Professor Stephen Bottomley
The Protein Production Unit provides a dedicated service to
academic and industry clients who wish to outsource protein
production and quality assurance.
In 2011, over 1850 individual proteins were produced and
purified in this facility from a variety of recombinant sources.
These proteins, which were isolated with the aid of liquid
handling robots, were used for antibody and vaccine production,
structural biology studies and biomedical/biophysical research.
Facilities and Centres
In our custom-built facility we provide the following services:
protein purification, refolding of insoluble proteins, expression
scouting and purification protocol development. We can
also customise high throughput methods for our clients and
recommend approaches to stabilise or refold proteins.
In 2011, we purchased an AKTA avant 25 FPLC scouting unit to
assist with the development of purification protocols. In 2012,
we will be able to offer a full range of expression vehicles for the
expression and purification of recombinant proteins from E.coli,
yeast, insect and mammalian cells.
This facility is operated by Dr Noelene Quinsey and Mr Nik
Sotirellis under the direction of Professor Stephen Bottomley.
Centres
ARC Centre of Excellence in Structural
and Functional Microbial Genomics
Director: Professor Ben Adler
The ARC Centre of Excellence in Structural and Functional
Microbial Genomics brings together a team of internationallyrenowned researchers with complementary expertise from the
School of Biomedical Sciences at Monash University.
As part of National Science Week, the ARC Centre in Structural
and Functional Microbial Genomics organised a public lecture at
BMW Edge, at Federation Square. Dr Paul Johnson from Austin
Health presented the lecture The End of Antibiotics, which was
followed by a panel discussion and questions from the public.
We research microbial pathogens and the hosts they infect,
focussing on diseases of importance to the Australian
primary industry. We aim to develop new veterinary vaccines,
diagnostics tests, and identify novel antimicrobial drug targets.
We use a genomics-based approach to identify virulent genes
of pathogens, and then seek to understand the structure and
function of the proteins they produce and how these organisms
cause disease.
We work collaboratively with scientists in Australia and
internationally and we also partner with Pfizer Animal Health and
Intervet Schering-Plough.
Recently we:
•• Registered a fowl cholera vaccine to be used in the market;
From left to right: Dr Noelene Quinsey, Mr Nik Sotirellis and Professor Stephen Bottomley.
http://proteinproductionunit.med.monash.edu.au
Protein Production Unit laboratory space.
•• Identified a new sub-population of T-cells in the immune
system;
•• Demonstrated that a larval-specific antigen against the
parasitic worm, Haemonchus contortus protects vaccinated
sheep in the field;
•• Solved the structure and genetic basis of cell surface
lipopolysaccharide assembly in all 16 known serotypes of
Pasteurella multocida, the cause of fowl cholera;
Development of therapeutics, diagnostics and vaccines against microbial
pathogens using the Centre’s research infrastructure and expertise.
•• Discovered how mammalian cells overcome infection with
Burkholderia pseudomallei, the cause of melioidosis;
•• Solved the structures of two important malarial virulence
factors in complex with novel compounds; and
•• Identified a candidate vaccine for sheep footrot.
www.microbialgenomics.net
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Annual Report 2011
Monash Comprehensive Cancer
Consortium
Interim Research Director: Professor Neil Watkins
Advisory Council Chair: Professor David de Kretser AC
Management Committee Chair: Professor Gail Risbridger
Chief Operating Officer: Ms Anna Kilgour
The Monash Comprehensive Consortium (MCCC) is one of three
major cancer research nodes in Victoria’s system of integrated
cancer research and care, and services approximately 30 per
cent of Victoria’s cancer patients.
MCCC partner organisations include Monash University,
Monash Institute of Medical Research, Prince Henry's Institute,
Southern Health, Alfred Health, Cabrini Health, Peninsula Health
and Southern Melbourne Integrated Cancer Services. The
consortium’s role is to bring together the research and clinical
strengths of its partners to deliver the best possible outcomes
for cancer patients.
www.mccc.edu.au
Monash Obesity and Diabetes Institute
Director: Professor Michael Cowley
The Monash Obesity and Diabetes Institute (MODI™) comprises
of obesity, diabetes and metabolic disease researchers who aim
to translate research results into clinical treatments for these and
related disorders. The Institute is embedded within the School
of Biomedical Sciences, which facilitates collaborations with
scientists in several departments.
MODI™ also hopes to raise the profile of obesity and diabetes
awareness in the community and the need to tackle these
problems as what we are doing now is not working.
Key focus of research groups:
Professor Michael Cowley is the Director of MODI™ and is
interested in the hormone leptin, which our fat cells secrete
to control appetite, metabolism and body weight. He is
investigating if high leptin levels in obese mammals contribute
to pathologically high blood pressure, increased heart rate and
diabetes. If so, it may be possible to develop treatments that
improve a patient's metabolic condition by blocking
leptin action.
www.modi.monash.edu.au/
92
Professor Tony Tiganis studies the regulation of insulin
signalling in the brain and how inflammation contributes to the
development of diabetes and obesity.
Associate Professor Matthew Watt uses genetic and
pharmacological approaches to investigate the link between
obesity and the development of Type 2 diabetes.
Professor Brian Oldfield studies the role that the brain plays
in controlling food intake and the burning of energy, which
ultimately leads to changes in body weight and possibly obesity.
Professor Iain Clarke investigates how hormones in the brain
control metabolic function, food intake, and their role in obesity.
Grants and
Funding
>> National and international
research support
>> Patents
Grants and Funding
2006
2007
2008
2009
2010
2011
NHMRC Projects
$7,101,926
$9,984,961
$10,581,847
$11,060,072
$13,676,111
$16,196,688
NHMRC Programs
$5,259,252
$5,970,800
$7,464,703
$7,030,448
$7,189,305
$6,009,845
$437,470
$786,720
$1,225,460
$606,123
$1,421,647
$4,990,393
$5,524,382
$5,718,726
$6,472,863
$6,786,280
$6,593,196
$17,351,572
$21,917,614
$24,551,996
$25,788,843
$28,257,819
$30,221,376
ARC Projects (Discovery and Linkage)
$2,761,966
$2,314,257
$2,934,206
$4,637,308
$5,184,242
$5,304,060
ARC Centres
$1,826,565
$2,314,952
$2,468,678
$3,048,225
$2,814,765
$1,602,734
ARC Fellowships and Scholarships (people support)
$158,111
$322,625
$663,380
$1,105,422
$1,264,116
$2,094,133
ARC Other (Infrastructure and Equipment Grants)
$724,660
$1,700,000
$400,000
$1,400,000
$485,695
$829,140
$5,471,302
$6,651,834
$6,466,264
$10,190,955
$9,748,818
$9,830,067
NIH, NHF, CRC, AKF and donations
$16,416,182
$20,434,059
$14,149,547
$9,036,248
$10,623,115
$8,726,203
Total Income
$39,239,056
$49,003,507
$45,167,807
$45,016,046
$48,629,752
$48,777,646
NHMRC Grants Income
NHMRC Other (Development and Equipment Grants)
NHMRC Fellowships and Scholarships (people support)
NHMRC Total
ARC Grants Income
ARC Total
Other National and International Income
Annual Report 2011
Grants and Funding
Research Income 2006 to 2011
Major Grants Commencing in 2012
Source
Chief Investigator and Project Title
ARC Discovery Grants
Funding ($ million)
24.5
22.0
17.3
20.4
16.4
6.6
Period
Total
Funds
Beddoe T: Host-pathogen interactions: The role of mimicry.
3
2012-2014
$180,000
Bird P: The role of the protease inhibitor Serpinb9 in antigen cross-presentation by dendritic cells.
3
2012-2014
$315,000
Clarke I: Muscling in on the brain.
3
2012-2014
$270,000
Clarke I: Endogenous and environmental regulation of energy expenditure in skeletal muscle.
3
2012-2014
$540,000
Coulibaly F: Spindles of insect viruses: Structure, function and engineering of natural protein crystals
3
2012-2014
$315,000
Dunstone M: The mechanism of pore formation by membrane attack complex/perforin-like proteins.
3
2012-2014
$280,000
Mackay C: Mechanisms connecting diet, metabolism, gut microbiota and immunity.
3
2012-2014
$345,000
Meeusen E: Designing new generation adjuvants for allergy and parasite vaccines.
3
2012-2014
$315,000
O'Bryan M: HEN1 is a regulator of piRNA metabolism, transcriptional regulation and mammalian male
3
2012-2014
$344,000
3
2012-2014
$270,000
Bakola S: Understanding the function of a visual pathway to the limbic cortex.
3
2012-2014
$375,000
Furic L: Estrogen-mediated regulation of gene expression via transcriptional and translational control:
3
2012-2014
$375,000
Jeffrey K: Argonaute proteins and the mammalian antiviral response.
3
2012-2014
$375,000
Borg N: The regulation of anti-viral immunity by host and viral proteins.
4
2011-2015
$634,528
Spencer S: Developmental programming of adult stress responses: Early life nutrition permanently
4
2011-2015
$ 707,797
as microparticles for vaccine delivery.
14.1
5.5
Duration
(Years)
6.5
fertility.
Smith J: The critical role of kisspeptin/neurokinin/dynorphin (KNDy) neurons in gonadotropin releasing
2006
2007
hormone (GnRH) release.
2008
ARC Early Career
Fellowships
30.2
28.3
25.8
Complementary, synergistic or opposing responses?
ARC Future
Funding ($ million)
Fellowships
alters stress and immune function.
10.2
9.0
9.7
10.6
9.8
8.7
ARC LIEF Grant
Whisstock J: A centre for structural cryo-electron microscopy.
1
2012
$640,000
ARC Linkage Grant
Meeusen E: Exploiting the lymphatic system for next generation vaccine development.
3
2012-2014
$570,000
NHMRC Career
Polo J: Determining the events that occur during the reprogramming of different adult cells into
4
2012-2015
$391,076
Development Award
embryonic stem-like cells and the capacity of becoming another specific adult cell during this process.
Aljofan M: New targets for antiviral therapies.
4
2012-2015
$294,892
Berry R: The mechanism responsible for quality control in the immune system.
4
2012-2015
$294,892
Lawrence M: Stem cells in the prostate cancer microenvironment.
4
2012-2015
$294,892
Robertson A: Understanding the relationship between cellular sterols and amyloid toxicity that occurs
4
2012-2015
$320,628
Rossjohn J: Australia Fellowship.
5
2012-2016
$4,000,000
Buckle A: Research Fellowship SRF B.
5
2012-2016
$641,855
Fellowship
NHMRC Early Career
Fellowships
2009
2010
2011
in many neurodegenerative diseases.
NHMRC Total
ARC Total
Other National and
International Income
Research Income 2011
NHMRC Fellowships
Oldfield B: Reserch Fellowship PRF.
5
2012-2016
$702,795
NHMRC Project
Andrews Z: Carnitine palmitoyl transferase 1 in POMC neurons controls glucose homeostasis and
3
2012-2014
$458,510
Grants
body weight.
Andrews Z: Hormonal regulation of NPY neurons in the arcuate nucleus of the hypothalamus.
3
2012-2014
$564,680
Anthony R: SIGN receptors and the antiinflammatory activity of sialylated IgG Fcs.
3
2012-2014
$536,325
Bertram J: Understanding the causes of childhood congenital anomalies of the kidney and
3
2012-2014
$589,700
Clarke I: Gonadotropin inhibitory hormone (GnIH); a negative regulator of reproduction.
3
2012-2014
$727,425
Cowley M: Can blockade of leptin action in the brain reduce blood pressure in obese mice?
3
2012-2014
$631,010
Denton K: Consequences of elevated maternal glucocorticoids for early childhood renal
3
2012-2014
$584,685
Evans R: The role of tissue hypoxia in the evolution of kidney disease.
3
2012-2014
$492,308
Jans D: The essential nuclear transporter Importin 13: Key role in brain and testis.
3
2012-2014
$592,350
Jans D: Enhanced nuclear transport in transformed cells: Implications for cancer treatment.
3
2012-2014
$607,350
Jeffrey K: Argonaute proteins in the mammalian antiviral response.
3
2012-2014
$505,586
Kaiserman D: Investigating the role of SERPINB6 in cochlear function and deafness.
3
2012-2014
$550,850
Law R: Structural studies on plasminogen.
3
2012-2014
$346,175
Loveland K: Hedgehog signalling in spermatogenesis.
3
2012-2014
$506,175
urinary tract.
Other National and
International Income: 18%
development and function.
ARC Total: 20%
96
NHMRC Total: 62%
97
Annual Report 2011
Grants and Funding
Major Grants Commencing in 2012
Source
Chief Investigator and Project Title
NHMRC Project
School of Biomedical Sciences Patents 2011
Duration
(Years)
Period
Total
Funds
Lyras D: Novel therapeutic and preventive strategies for Clostridium difficile infections.
3
2012-2014
$491,325
Lyras D: Expression and secretion of large clostridial toxins from the pathogenic clostridia.
3
2012-2014
$321,175
McMenamin P: Mechanisms of Novel TLR9 mediated intraocular inflammation.
3
2012-2014
Mitchell C: Phosphoinositide 3-kinase signalling and skeletal muscle mass.
3
Naderer T: Diabolic regulation of macrophage cell death pathways by Legionella.
Title
Filing Date
R Rajan , L Marsden
Provisional
Monash owned
Constrained immunogenic compositions and uses.
23/06/11
F Coulibaly, A Mansell, R Ffrench
PCT
Jointly owned
Detection of EPHA3 as a marker of the presence of a solid tumor.
20/06/11
M Lackmann, C To
National phase US
Licensed
$427,260
X-ray crystal structure of human plasminogen.
08/06/11
J Whisstock, R Law, P Coughlan
Provisional
Monash owned
2012-2014
$577,350
A method for enriching cardiomyocytes.
01/06/11
D Elliott, A Elefanty, E Stanley
Provisional
Jointly owned
3
2012-2014
$596,010
Crystal structure of perforin and methods for its use. Method of
17/05/11
J Whisstock, R Law, J Trapani,
PCT
Jointly owned
O'Bryan M: Katanin p80 is a key regulator of microtubule dynamics and male fertility.
3
2012-2014
$582,350
crystallising perforin.
Rajan R: Sensory cortex processing changes underlying brain and behaviour deficits caused by
3
2012-2014
$557,760
Diagnostic and prognostic assay for breast cancer.
PCT
Monash owned
PCT
Monash owned
Rajan R: Understanding the role of caudal auditory belt areas in perception of complex sounds.
I Voskoboinik
03/02/11
3
2012-2014
$747,221
Risbridger G: Estrogen therapy for castrate resistant prostate cancer.
3
2012-2014
$513,675
Rosa M: Understanding the organisation of the medial parietal cortex: Sensorimotor integration for
3
2012-2014
$533,510
3
2012-2014
$571,010
Smyth I: Involvement of the Asciz gene in kidney development and disease.
Taylor R: Stromal hedgehog signalling in prostate cancer.
3
2012-2014
$311,175
Traven A: An investigation into pathogen specific factors required for drug resistance and viability of
3
2012-2014
$326,175
Widdop R: Insulin regulated aminopeptidase: A new cardiovascular target.
3
2012-2014
$649,685
Coulibaly F: Immunogenicity study of HIV Env MicroCubes.
1
2011-2012
$109,000
Methods for regulating blood glucose levels.
25/01/11
HIV and Hepatitis
A method for treating obesity.
16/07/10
T Tiganis, M Cowley
PCT
Monash owned
Cell culture media.
08/04/10
A Elefanty
US only
Monash owned
A method of treating diabetes by inhibition of TCPTP in the liver.
02/02/10
T Tiganis, M Tremblay,
Provisional
Monash owned
S McGowan, C Porter,
National Phase AU,
Jointly owned
J Whisstock, J Lowther,
EP and US
S Andrikopoulos
Crystal structures of malarial aminopeptidase or M1 malaria protein.
12/02/09
Jans D: Nuclear transport Inhibitors as HIV anti-virals.
1
2011-2012
$113,000
Netter H: Immunogenicity of virus-like particles contaning HIV-1 neutralising epitopes and
1
2011-2012
$112,000
1
2012
$74,175
determination of the quality of the immune response.
Ramaciotti
Vinh A: Defining hypertension down to the T cell.
1
2012
$68,000
McMenamin P: The role of resident corneal immune cells in the development of diabetes associated
1
2012
$59,991
1
2012
$52,340
body insulin resistance?
Broughton B: How does G Protein-Coupled Receptor 30 (GPR30) affect stroke outcome?
2
2012-2013
$210,000
Blood Pressure
EphA3 antibodies for the treatment of solid tumours.
Sobey C: Using human amnion stem cells to treat stroke.
2
2012-2013
$130,000
J Whisstock, S McGowan,
National Phase,
A Buckle
US only
J Rood, A Keyburn
National Phase,
Jointly owned
Assigned
M Lackmann, C To
National Phase CN
Licensed
AU, EP, NZ and US
Identification of candidate vaccine antigens from Dichelobacter nodosus
19/12/07
(footrot vaccine).
Regulation of metalloprotease cleavage of cell surface proteins.
13/09/07
19/12/05
J Rood, K al-Hasani, J Boyce,
National Phase AU,
D Parker
EP, NZ and US
J Whisstock, R Law, A Buckle,
National Phase
G Fenalti, M Rowley
US and EP
M Lackmann, PW Janes, DB
National Phase.
Nikolov, N Saha
Granted US
Monash owned
Monash owned
Jointly owned
and NZ.
Methods for producing blood products from pluripotent cells in
19/11/04
E Stanley
cell culture.
Eph/ephrin mediated modulation of cell adhesion and tumour
A method of modulating cellular activity and molecules for use therein.
Clostridium expression system.
98
10/03/08
Granted AU.
Monash owned
Pending in US.
09/02/04
cell metastasis.
Research
Heart Foundation
06/06/08
corneal neuropathy.
Watt M: Does lipid accumulation in hypothalamic neurons contribute to the development of whole-
Foundation for High
02/07/08
US only
Crystal structures of both isoforms of GAD.
Foundation
Research Trust
C Stack, S Donnelly, J Dalton
Octameric protein in bionanotechnology.
Clostridial toxin netB.
Virology Research
M Cowley, P Enriori, R Brown,
I Clarke, B Henry, M Rudaz
Candida albicans.
Bertram J: Optical Projection Tomography (OPT) machine.
T Tiganis, B Shields, C McLean,
R Sutherland
goal directed behaviour.
Diabetes Australia
Status
18/11/11
traumatic brain injury.
Clive and Vera
Patent
Surgical implant tool.
Grants
Australian Centre for
Monash Inventor/s
04/09/03
06/04/98
M Lackmann, S Wimmer-
National Phase US
Kleikamp, A Scott, C Vearing,
and EP. Granted
A Boyd
in AU.
M Aguilar, P Perlmutter, J
National Phase AU
Rossjohn, A Purcell
and US
J Rood, D Lyras
Granted in US
Jointly owned
Jointly owned
Licensed
99
Education
>> Teaching news
>> Staff and student programs
>> Centre for human anatomy education
>> Awards and prizes
First year Bachelor of biomedical science and double-degree students
at Transition Day.
Annual Report 2011
Education
Education in the School of Biomedical Sciences (SOBS)
Professor Phillip Nagley:
Chair of School Education Committee,
Director of Biomedical Education Advancement Unit
Associate Professor Yvonne Hodgson:
Manager of Academic Programs and Quality, School of
Biomedical Sciences
Associate Professor Marilyn Baird:
Head, Department of Medical Imaging and Radiation Sciences
and Convenor, Bachelor of Radiography and Medical Imaging
Professor Paul McMenamin:
Director, Centre for Human Anatomy Education
School education committee
Our committee held 10 meetings during 2011.
We achieved the following:
• Developed policy to maintain international best practice in
teaching, learning and assessment;
• Plannied upgrade of learning spaces in the
School educational precinct;
• Supported the transition of academic staff to newly
introduced education-focussed roles;
• Explored ways to enhance the already substantial links
between undergraduate education and biomedical research;
and
Biomedical education advancement unit
This unit focuses on educational leadership and staff development
and is led by Professor Phillip Nagley, with Dr Sharon Flecknoe
and Jane Sun. Jane left in August to accept a position in another
faculty.
BEAU works closely with the SOBS Education Committee,
networks with educators in Biomedical Science and undertakes
specific projects on behalf of the School.
BEAU:
• Helped Bioscience staff at Monash Peninsula campus achieve
their educational goals in Allied Health, including incorporating
Bioscience teaching into the new Nursing program at
Berwick campus;
Overview of undergraduate teaching
The School teaches students enrolled in diverse undergraduate
and professional postgraduate courses. In 2011, the net
undergraduate and postgraduate coursework teaching generated
approximately $12.2 million income for the School and its
associated partners.
The School manages undergraduate programs in two disciplines:
Biomedical Science, and Radiography and Medical Imaging.
The 2011 income generated by the Biomedical Science course
and its associated programs (Scholar, Advanced Honours, BMS
Honours and the doubled degree programs) was approximately
$4.1 million, with an additional $1.4 million from the Radiography
and Medical Imaging undergraduate course. About 35% of
the total income is passed on to faculty and non-faculty
School partners.
• Provided staff development opportunities, enhancing
educational skills and experience;
Teaching income from non-School managed courses generated
a further $8.2 million for the School. The largest income ($5.3
million) was provided by departmental teaching of BSc units,
including the BSc Honours units. Teaching of MBBS and allied
health students at the Peninsula campus generated a further
$2.1 million and $0.8 million for the School, respectively.
• Combined work experience placements for high school
students with a leadership program for postgraduate students
at SOBS;
In 2011, the School supervised 109 students undertaking
honours programs (BSc 60, BMS 49). The breakdown of
teaching load and School income is shown in the table below.
• Maintained close links with John Monash Science School and
delivered both Biomedical Science and bioinformatics electives
at this new secondary school; and
• Ran the BioEYES program involving zebrafish developmental
biology in several primary and secondary schools.
• Developed and implemented improved units for nursing
students at Monash Peninsula and Gippsland campuses.
Net School/
Department Income
in 2011
School Managed Courses
Enrolments
Total Biomedical Science Courses
766
$2,597,784
Radiography and Medical Imaging Courses
222
$897,796
Teaching in Non-School Managed Courses
EFTSL#
Science Units
654
$5,276,505
MBBS Teaching
385
$2,075,505
Peninsula Teaching
103
$834,752
Total Undergraduate Teaching Income
Postgraduate School Courses
Medical Imaging and Radiation Sciences
Net Coursework Teaching Income
$11,682,313
Enrolments
91
$564,933
$12,247,246
#EFTSL: Equivalent Full Time Student Load
Work experience student Simon Zhing (left) with postgraduate mentor Katrina Mirabito (right).
102
John Monash Science School students engrossed in BioEYES work.
103
Annual Report 2011
Education
Biomedical science programs
Undergraduate research programs
August 2011 saw the inaugural meeting of the Biomedical
Science Advisory Board. The Board consists of current and
former students, industry members and staff from representative
graduate courses. The feedback from the Advisory Board was
positive and the minutes of the meeting were presented to
the Faculty.
Undergraduate students were welcomed into School laboratories
through the Research in Action units offered by the departments
of Anatomy and Developmental Biology, Biochemistry and
Molecular Biology, Microbiology, Monash Immunology and Stem
Cell Laboratories, Pharmacology and Physiology. 71 third year
undergraduate students completed small research projects
over one semester in diverse biomedical areas. These units are
popular, with a 51% increase in students choosing these units in
the past four years.
Also in 2011, Monash Biomedical Science students participated
in a benchmarking survey with the University of Queensland.
Final year students were asked about skill acquisition during their
studies. Results from the Monash survey were presented at the
Assessment Institute in Indianapolis by the Course Convenor,
Associate Professor Yvonne Hodgson.
Now in its second year, the Talented Student Program
continues to grow, with 33 students enrolled. This program
identifies and nurtures high-achieving students who are interested
in pursuing a career in medical research. They are exposed
to research programs and researchers through extracurricular
activities: mentoring, research platform tours and seminars.
This year, students toured the Australian Synchrotron and the
Monash flow cytometry facility - FlowCore. The program is open
to students enrolled in the Bachelor of Biomedical Science
Scholars or the Bachelor of Biomedical Science Advanced
Honours Program.
The Bachelor of Biomedical Science Honours program,
convened by Associate Professor Tim Cole, attracted 53 students
into the School to undertake a research project. The students
excelled, with 69% achieving a grade of First Class Honours.
Radiography and medical radiations
programs
In 2010, the Master of Medical Radiations program replaced
the Nuclear Medicine stream with a new stream in Medical
Ultrasound. With funding support from I-MED MIA Victoria, we
have been able to develop new course materials and provide
supervised clinical placements, which is critical for student
learning.
Philips Healthcare has also generously provided three ultrasound
machines for a new ultrasound teaching laboratory, which will
help students develop their pre-clinical skills.
The Medical Ultrasound stream has been accredited by the
Australasian Sonographers Accreditation Registry for the
maximum period of five years. Currently, the Radiation Therapy
stream is undergoing its re-accreditation process with the
Australian Institute of Radiography.
Enrolment numbers in the Bachelor of Radiography and Medical
Imaging course have been steadily increasing, with over 60
students in years one and two. As a result, the curriculum has
been modified in year four. From 2012, students electing to study
RAD4080 Selected Topics in Medical Imaging will be able to
choose one of the following streams: advanced CT; advanced
medical ultrasound; paediatric imaging and professional
education and leadership.
Graduates from the Bachelor of Radiography and Medical
Imaging continue to enjoy full employment upon graduation.
Also, it was pleasing to learn that in the recent National Course
Experience Questionnaire overall satisfaction with the course was
95%, with just under a 50% response rate.
Throughout 2011, considerable planning has taken place
regarding the new radiography teaching laboratory which will
incorporate clinical quality imaging systems.
International programs
The articulation program with the Republic Polytechnic in
Singapore continued in 2011. This program has been in place
since 2006 and has seen a total of 82 students come to Monash
to undertake the third year of the Biomedical Science degree
course. About one-third of these students stay at Monash to
complete honours, PhD and other postgraduate courses. To
date, 19 students have enrolled in Biomedical Science Honours,
2 students have undertaken a Graduate Diploma in Reproductive
Sciences, 5 students have completed a Master of Biomedical
Science part one, 2 have completed a Master of Biomedical
Science and 2 students have undertaken a PhD.
In addition to the Republic Polytechnic program, the School
also teaches international students who undertake degree
programs in Biomedical Science and Science. For the Biomedical
Science course, approximately 4% of students are international:
3% are from New Zealand and 5% are permanent residents.
Our school also teaches several units at the Malaysia Sunway
campus. These units are taught by staff in the departments of
Microbiology (MIC2011) and Physiology (PHY2021 and PHY2032)
and contribute to the Bachelor of Medical Bioscience course.
Teaching across campuses requires effective communication
and collaboration between Clayton-based staff and those at the
Malaysian campus.
Student support
The School organised the annual one-day transition program
for first year students in February. Approximately 200 students
attended this transition program, which focused on helping
students form new friendships, meet staff and senior students,
and become familiar with the campus. The program featured
a treasure hunt, trust games and a mini film festival. Sharon
Flecknoe and Jane Sun, from BEAU, worked closely with program
director Associate Professor Yvonne Hodgson to organise and
run the program. Also, higher year biomedical science students
led each group of first year students, while postgraduate students
in the School acted as tutors for each of the scheduled activities.
This is an important program as feedback from participants
indicate that this program helps students transition successfully
into university life.
In 2011, the School continued to support the student-run
Biomedical Science Society, which organises events, including:
an annual camp for biomedical science students, industry mixer
nights, University Open Day activities and Transition Program.
The society plays an important role in the social and academic
lives of biomedical science students.
The 2011 Biomedical Science honours class.
104
Simulated learning at Monash Medical Centre.
Biomedical sciences students modelling DNA.
105
Education
PASS program
Centre for human anatomy education
The Peer-Assisted Study Session (PASS) program continued in
2011 for first year students enrolled in BMS1021 and BMS1062.
This initiative, which is organised by Adrian Devey from the
Vice Chancellor (Education) office, allows high achieving senior
students to act as student mentors and give weekly tutorials
sessions to first-year students. The students, who participated in
the program, interacted with older peers and enjoyed the informal
tutorial sessions.
The Centre delivers anatomy teaching to students studying
medicine at three Monash campuses: Clayton, Gippsland and
Malaysia, Kuala Lumpar.
In 2011 one of the Biomedical Science PASS Leaders, Claudia
Ashkar, won the Australasian PASS Leader Award, the first time
that Monash was successful on the international stage. Claudia
received her award at the National PASS Forum in Sydney
in September.
Student awards and prizes
The 2011 Faculty Prizes and Award Ceremony for Academic
Excellence was held in April. The top two students from each
year in the Bachelor of Biomedical Science course received $200
and the top student from the honours program received $500.
Industry and professional bodies support the radiography course
and provide at least two $200 prizes in each year level of
the course.
Biomedical science teaching newsletter
The Centre for Human Anatomy Education was recently reviewed
and the activities in both teaching and research were highly
commended. A number of recommendations were made that will
allow the Director Professor Paul McMenamin to continue to push
for changes in learning and teaching activities in the Centre. The
goal is to make it an exemplar internationally when it comes to the
practice of anatomy teaching and as a leader in innovation and
research in this field.
Recently, the Learning Resource area has had some cosmetic
changes. There have been alterations to the entrance and
teaching spaces to make them more appealing and interesting
for students.
In other news, Dr Colin McHenry, who has research interests
in comparative vertebrate morphology and computational
biomechanics, recently joined the Centre and will strengthen our
anatomical sciences research. He studies diverse species, from
sharks to lizards and humans.
Staff professional development
and support
Two issues of the School newsletter were written by Thomas
Dillane and edited by Associate Professor Yvonne Hodgson. The
publications, which were distributed to staff and students, profiled
young researchers and described trends in teaching and related
topics. In 2009, the newsletter was incorporated into the School’s
publication Biomed Benchmark.
Demonstrator/tutor training
Teaching facilities and equipment
Bioscience education scholarship team
Refurbishment and upgrades of facilities
The ground floor of Building 13D is currently being renovated to
accommodate an X-ray laboratory and teaching laboratories for
Radiography and Medical Imaging students. Work is expected to
be completed by the end of January 2012. Plans for upgrading
other areas of the SOBS teaching precinct are in progress.
New practical class equipment
In 2011, the Department of Physiology replaced the power lab
set-ups in all teaching laboratories. A total of 30 life science
power lab and lab tutor set-ups were purchased from AD
Instruments at an approximate cost of $10,000 each. The new
equipment is being used for second and third year practical
classes for students studying BSc, BMS, Nutrition and
Radiography courses, and also for new practical classes for
MBBS students.
Claudia Ashkar with her Australasian PASS Leader Award.
The training program for sessional staff (demonstrators) was run
in semesters one and two for 47 and 20 staff, respectively. All
incoming student demonstrators and tutors, who teach units
delivered by SOBS departments, receive training in practical and
small group teaching.
Collaborative university biomedical
education network
In 2011, Associate Professor Yvonne Hodgson and Dr Janet
Macaulay successfully obtained an ALTC Discipline Learning and
Teaching Network grant as team members of the Collaborative
University Biomedical Education Network (CUBENET). This
national network will foster dialogue, communication and
collaboration with tertiary biomedical educators, both nationally
and internationally, and create a sustainable, innovative
biomedical curriculum that addresses the challenges that face
the sector.
At the heart of CUBENET will be a website and newsletter
featuring updates from working parties, reports, lectures by
visiting academics, and information about strategic funding
opportunities and participating partners. CUBENET will also
organise workshops, retreats and forums, the first of which
will be the National Biomedical Education Forum in Canberra,
in December 2011.
Education awards
On 2 March, Dr Richard Loiacono from the Department of
Pharmacology received the Dean’s Awards for Excellence in
Education (Quality) from Professor Steve Wesselingh. Dr Loiacono
was acknowledged for the outstanding quality of his teaching
activities and unit coordination. His long-standing commitment
to student-focussed learning is reflected by MonQueST teaching
surveys ranking him one of the top lecturers at Monash University.
Dr Loiacono teaches pharmacology in Biomedical Science,
Medicine, Science, Radiography and Neuroscience courses.
The Bioscience Education Scholarship Team (BEST) was formed
in 2010 to provide a forum for educators with an interest in
education research to discuss pertinent issues in higher education
and to establish collaborative projects. In 2011 BEST held 10
meetings. At the end of 2011 BEST established an international
arm, extending membership to staff at Purdue University in
the US.
Also in 2011, the Office of the Pro-Vice Chancellor (Learning and
Teaching) formed a network of staff participating in excellence in
education research, called MEERG. All members of BEST have
since joined this university-wide group.
Measuring energy expenditure by indirect colorimetry.
An example of body painting performed by a group of life drawing artists.
107
Postgraduate
Research
>> MBio graduate school
>> Higher degree research enrolments
and completions
>> Scholarships
Postgraduate Research
2009
2010
2011
Department of Anatomy and Developmental Biology
28
31
31
Department of Biochemistry and Molecular Biology
109
110
111
6
11
11
Department of Microbiology
47
51
56
Monash Immunology and Stem Cell Laboratories
32
30
28
Department of Pharmacology
28
22
25
Department of Physiology
37
30
30
287
285
292
Anatomy and Developmental Biology
11
5
7
Biochemistry and Molecular Biology
18
28
18
1
1
1
10
9
7
MISCL
8
5
3
Pharmacology
7
5
7
Physiology
10
6
11
Total
65
59
54
PhD and Masters by Research enrolments* in SOBS Departments
Department of Medical Imaging and Radiation Sciences
Total
PhD and Masters by Research completions* in SOBS Departments
Medical Imaging and Radiation Sciences
Microbiology
*Head count as at 31 December each year
Annual Report 2011
Postgraduate Research
Associate Professor Sharon Ricardo:
Director, MBio Graduate School
Dr Shae-Lee Cox:
Senior Project Manager, MBio Graduate School
MBio graduate school
In 2011 the MBio Graduate School provided enhanced scientific
and professional development training for the 292 Higher Degree
Research (HDR) students enrolled in the School of Biomedical
Sciences and Australian Regenerative Medicine Institute, at the
Monash Clayton campus.
HDR enrolments have remained consistent over the past three
years as shown in the table on page 109. We also include HDR
student completion data.
Highlights
Scholarships
In 2011, the MBio Graduate School continued to perform strongly
in the end-of-year postgraduate scholarships round, successfully
obtaining 36 out of 101 university-wide stipend scholarships
awarded to the Faculty. We also received one of the Faculty
postgraduate excellence awards that are offered to the top eight
applicants on the Faculty’s order of merit list.
International students did exceptionally well, with six students
receiving tuition fee scholarships out of the 12 awarded to the
Faculty. Students came from Sri Lanka, Malaysia, South Africa,
Iran, Vietnam, Brunei Darussalam, Peru and Mauritius to study in
the School.
Our students also received three NHMRC postgraduate
scholarships to undertake postgraduate studies in the
Departments of Biochemistry and Molecular Biology, and
Physiology.
Under the direction of Associate Professor Sharon Ricardo, we
have initiated the following:
Scholarship
•• Published a regular e-bulletin for HDR students, promoting
HDR activities and events;
Australian Postgraduate Award
17
•• Developed candidature confirmation process guidelines
to ensure consistent training, milestone reporting and
support for students across departments;
Monash Graduate Scholarship
6
Faculty Postgraduate Research Scholarship
6
Endeavour International Postgraduate Research
Scholarship
1
Monash International Postgraduate Research
Scholarship
4
Faculty of Medicine International Postgraduate
Scholarship
2
NHMRC Postgraduate Scholarships
3
•• Hosted mental health awareness seminars for staff
and students;
•• Provided dedicated writing spaces for students to complete
their theses; and
•• Initiated a PhD leadership program, together with BEAU,
for HDR students to mentor high school students from
John Monash Science School.
Student awards and prizes
This year, the MBio Graduate School hosted the inaugural
Anthony Koelmeyer International PhD Excellence Awards.
Three lucky PhD students received $1,500 each towards
international conference costs and research training in overseas
laboratories in order to enhance their PhD experience.
Total
Number
awarded
39
The MBio Graduate School is grateful for the funding support
from the Office of the Deputy-Vice Chancellor (Research),
Faculty of Medicine, Nursing and Health Sciences and School of
Biomedical Sciences.
For more information about us, please refer to our website at
www.med.monash.edu.au/mbio-gradschool/.
The successful students were:
•• Andrew Clarke, Department of Biochemistry
and Molecular Biology;
•• Sarah Hass Lockie, Department of Physiology; and
•• Jeffrey Moore, Department of Pharmacology.
We also hosted the annual Three Minute Thesis competition
for HDR students. Mohsin Sarwar, from the Department of
Pharmacology, was the winner and received a $600 travel
grant. Second and third places were awarded to Priyangi
Alwis (Department of Microbiology) and Sarah Wilkinson
(Department of Anatomy and Developmental Biology),
respectively. First and second prize winners went on to
represent SOBS in the faculty final.
Anthony Koelmeyer Award recipients. From left to right: Jeffrey Moore, Sarah Haas Lockie and
Andrew Clarke.
110
Ghizal Siddiqui, a PhD student from the Department of Microbiology.
Administration
>> News
Annual Report 2011
School Administration
Mr Doug McGregor:
School Manager
Vicki Burkitt continues her contribution to the School in the
new role of Communications and Projects Officer.
2011 was again a significant year for School administrative staff.
Also, in the second half of 2011 the Biomedical sciences student
services team re-located to building 77 so that the School now
has a single reception area for both staff and students.
This team consisting of:
On 31 January, the University’s financial services enhancement
and HR business partnership models were implemented. Under
these models, most finance and all HR services were
consolidated under central University management in a hub-type
structure. In the case of SOBS, many staff previously in finance
and HR roles within the School transferred to the new structure
and continued to provide relevant services to the School, albeit
under new management. Other staff obtained new roles in other
hubs or took advantage of the voluntary severance package
offered in late 2010.
At the same time, the School animal ethics team was incorporated
into the Faculty animal ethics office and re-located to building 13C
under the management of the Faculty Office. The School’s Animal
Ethics Officer Jane McCausland left the School as part of this
restructure but subsequently returned to take up a new role as
Administration Officer in the School Office.
As a result of these changes, the School Office now comprises
a small group of staff, who provide general administration,
infrastructure services, marketing and communications, and
operational budget services to the School. This team is managed
by the School Manager Doug McGregor, while School
Finance Manager Alan Hunter oversees the School operational
budgets. Alan is supported by Kim Gan, a Senior Management
Accountant.
Dr Isabel Roberts continues in her role as Manager,
Infrastructure. She is supported by Building Managers Ian
McPherson and Jeff Wright, Assistant Building Manager Eddie
Kadir and Technical Officer John Peavey. During 2011, Isabel’s
team provided infrastructure support to the School as well as
CSIRO labs in building 75. They also continued to develop the
School media preparation and central wash facility in building
77. Supporting Isabel in these areas are Shubha Lakkola and
Radana Ninkovic.
School of Biomedical Sciences infrastructure team. From left to right: Ms Radana Ninkovic,
Mr Ian McPherson, Dr Isabel Roberts, Mr John Peavey, Ms Shubha Lakkola, Mr Jeffrey Wright,
Ms Renae Hayle and Mr Eddie Kadir.
114
Associate Professor Yvonne Hodgson
Manager of Academic Programs and Quality,
School of Biomedical Sciences.
Convenor, Bachelor of Biomedical Sciences
Dr Joanne Waring
Student Services Manager
Ms Natalie Seng
Course Administrator
Ms Leanne Sultana
Student Services Officer
supports the teaching activities within the School. These include
the following School programs: the Bachelor of Biomedical
Science, honours and four double degree courses, Bachelor of
Radiography and Medical Imaging and postgraduate offerings
in Medical Ultrasound, Nuclear Medicine and Radiation Therapy
from the Department of Medical Imaging and Radiation Sciences,
and the School’s involvement in the Bachelor of Science.
Office staff are responsible for student selection, admission,
enrolment and course completion. They are also available to
help students manage the various challenges associated with
University study.
School Staff. From left to right: Mr Alan Hunter, Ms Vicki Burkitt, Ms Leanne Sultana, Associate
Professor Yvonne Hodgson, Ms Jane McCausland, Ms Ico Ma, Ms Anne Sowersby, Ms Natalie
Seng, Dr Joanne Waring, Dr Sharon Flecknoe and Mr Doug McGregor. Absent: Mr Kim Gan.
Research
Publications
>> Papers
>> Book chapters
>> Reviews
Annual Report 2011
Research Publications
Number of publications
Primary 385
Books, Book Chapters and
Electronic Books 21
Reviews 31
Other 47
Total 484
Key:
ANT
Anatomy and Developmental Biology
BCH
Biochemistry and Molecular Biology
IMM-C
Immunology – Clayton
MICRO Microbiology
MISCL Monash Immunology and
Stem Cell Laboratories
MMI
Monash Micro Imaging
PHARM Pharmacology
PHY
Physiology
RAD
Medical Imaging and
Radiation Sciences
Primary
Aitken, R.J., J.K. Findlay, K.J. Hutt, and J.B. Kerr,
Apoptosis in the germ line. Reproduction, 2011.
141(2): p. 139-150 [ANT]
Albiston, A.L., S. Diwakarla, R.N. Fernando, S.J.
Mountford, H. Yeatman, B. Morgan, V. Pham, J.K.
Holien, M.W. Parker, P.E. Thompson, and S.Y. Chai,
Identification and development of specific inhibitors for
insulin-regulated aminopeptidase as a new class of
cognitive enhancers. Br J Pharmacol, 2011. 164(1): p.
37-47 [PHY]
Alcock, F., C.T. Webb, P. Dolezal, V. Hewitt, M.
Shingu-Vasquez, V.A. Likic, A. Traven, and T.
Lithgow, A Small Tim Homohexamer in the Relict
Mitochondrion of Cryptosporidium. Mol Biol Evol,
2011. E-pub: p. 113-122 [BCH]
Al-Deen, F.N., J. Ho, C. Selomulya, C. Ma, and
R. Coppel, Superparamagnetic Nanoparticles for
Effective Delivery of Malaria DNA Vaccine. Langmuir,
2011. 27(7): p. 3703-3712 [MICRO]
Ali, F., M.J. Rowley, B. Jayakrishnan, S. Teuber, M.E.
Gershwin, and I.R. Mackay, Stiff-person Syndrome
(SPS) and anti-GAD-related CNS Degenerations:
Protean Additions to the Autoimmune Central
Neuropathies. J Autoimm, 2011. 37: p. 79-87 [BCH]
Alikhan, M.A., C.V. Jones, T.M. Williams, A.G.
Beckhouse, A.L. Fletcher, M.M. Kett, S. Sakkal,
C.S. Samuel, R.G. Ramsay, J.A. Deane, C.A.
Wells, M.H. Little, D.A. Hume, and S.D. Ricardo,
Colony-Stimulating Factor (CSF)-1 Promotes Kidney
Growth and Repair via Alteration of Macrophage
Responses. Am J Pathol, 2011. 179(3): p. 1243-1256
[MISCL,PHY,BCH]
Alonzo III, F., B. Xayarath, J.C. Whisstock, and
N.E. Freitag, Functional analysis of the Listeria
monocytogenes secretion chaperone PrsA2 and
its multiple contributions to bacterial virulence. Mol
Microbiol, 2011. 80(6): p. 1530-1548 [BCH]
Altuntas, A.O., B. Dagge, T.Y. Chin, J.E. Palamara,
N. Eizenberg, R. Wolfe, and H.K. Graham, The
effects of intramuscular tenotomy on the lengthening
characteristics of tibialis posterior: high versus low
intramuscular tenotomy. J Child Orthop, 2011. 5(3): p.
225-230 [ANT]
Alvisi, G., O. Marin, G. Pari, M. Mancini, S. Avanzi,
A. Loregian, D.A. Jans, and A. Ripalti, Multiple
phosphorylation sites at the C-terminus regulate
nuclear import of HCMV DNA polymerase processivity
factor ppUL44. Virology, 2011. 417(2): p. 259-267
[BCH]
118
Ambaye, N.D., S. Pero, M.J. Gunzburg, M.Y. Yap,
D.J. Clayton, M.P. Del Borgo, P. Perlmutter, M.I.
Aguilar, G.S. Shukla, E. Peletskaya, M.M. Cookson,
D.N. Krag, M.C. Wilce, and J.A. Wilce, Structural
basis of binding by cyclic non-phosphorylated peptide
antagonists of GRB7 implicated in breast cancer
progression. J Mol Biol, 2011. 412(3): p. 397-411
[BCH]
Ambrosini, Y.M., G.-X. Yang, W. Zhang, M. Tsuda, S.
Shu, K. Tsuneyama, P.S.C. Leung, A.A. Ansari, R.L.
Coppel, and M.E. Gershwin, The multi-hit hypothesis
of primary biliary cirrhosis: polyinosinic-polycytidylic
acid (poly I:C) and murine autoimmune cholangitis.
Clin Exp Immunol, 2011. 166(1): p. 110-120 [MICRO]
Amps, K., P.W. Andrews, G. Anyfantis, L. Armstrong,
S. Avery, H. Baharvand, J. Baker, D. Baker, M.B.
Munoz, S. Beil, N. Benvenisty, D. Ben-Yosef, J.C.
Biancotti, A. Bosman, R.M. Brena, D. Brison, G.
Caisander, M.V. Camarasa, J. Chen, E. Chiao, Y.M.
Choi, A.B. Choo, D. Collins, A. Colman, J.M. Crook,
G.Q. Daley, A. Dalton, P.A. De Sousa, C. Denning, J.
Downie, P. Dvorak, K.D. Montgomery, A. Feki, A. Ford,
V. Fox, A.M. Fraga, T. Frumkin, L. Ge, P.J. Gokhale,
T. Golan-Lev, H. Gourabi, M. Gropp, L. Guangxiu, A.
Hampl, K. Harron, L. Healy, W. Herath, F. Holm, O.
Hovatta, J. Hyllner, M.S. Inamdar, A.K. Irwanto, T. Ishii,
M. Jaconi, Y. Jin, S. Kimber, S. Kiselev, B.B. Knowles,
O. Kopper, V. Kukharenko, A. Kuliev, M.A. Lagarkova,
P.W. Laird, M. Lako, A.L. Laslett, N. Lavon, D.R.
Lee, J.E. Lee, C. Li, L.S. Lim, T.E. Ludwig, Y. Ma,
E. Maltby, I. Mateizel, Y. Mayshar, M. Mileikovsky,
S.L. Minger, T. Miyazaki, S.Y. Moon, H. Moore, C.
Mummery, A. Nagy, N. Nakatsuji, K. Narwani, S.K.
Oh, C. Olson, T. Otonkoski, F. Pan, I.H. Park, S. Pells,
M.F. Pera, L.V. Pereira, O. Qi, G.S. Raj, B. Reubinoff,
A. Robins, P. Robson, J. Rossant, G.H. Salekdeh,
T.C. Schulz, K. Sermon, J.S. Mohamed, H. Shen, E.
Sherrer, K. Sidhu, S. Sivarajah, H. Skottman, C. Spits,
G.N. Stacey, R. Strehl, N. Strelchenko, H. Suemori,
B. Sun, R. Suuronen, K. Takahashi, T. Tuuri, P. Venu,
Y. Verlinsky, D.W. Oostwaard, D.J. Weisenberger,
Y. Wu, S. Yamanaka, L. Young and Q. Zhou,
Screening ethnically diverse human embryonic stem
cells identifies a chromosome 20 minimal amplicon
conferring growth advantage. Nat Biotechnol, 2011.
29(12): p. 1132-1144 [ANT]
Ang, C.S., J. Rothacker, H. Patsiouras, P. Gibbs,
A.W. Burgess, and E.C. Nice, Use of multiple reaction
monitoring for multiplex analysis of colorectal cancerassociated proteins in human feces. Electrophoresis,
2011. 32(15): p. 1926-1938 [BCH]
Arumugam, T.V., Y.L. Cheng, Y. Choi, Y.H. Choi, S.
Yang, Y.K. Yun, J.S. Park, D.K. Yang, J. Thundyil, M.
Gelderblom, V.T. Karamyan, S.C. Tang, S.L. Chan,
T. Magnus, C.G. Sobey, and D.G. Jo, Evidence that
{gamma}-secretase-mediated Notch signaling induces
neuronal cell death via the NF{kappa}B-Bim pathway
in ischemic stroke. Mol Pharmacol, 2011. 80(1): p.
23-31 [PHARM]
Astle, M.V., L.M. Ooms, A.R. Cole, L.C. Binge, J.M.
Dyson, M.J. Layton, S. Petratos, C. Sutherland, and
C.A. Mitchell, Identification of a proline-rich inositol
polyphosphate 5-phosphatase (PIPP): collapsin
response mediator protein 2 (CRMP2) complex that
regulates neurite elongation. J Biol Chem, 2011.
286(26): p. 23407-23418 [BCH]
Aurelio, L., A. Christopoulos, B.L. Flynn, P.J.
Scammells, P.M. Sexton, and C. Valant, The
synthesis and biological evaluation of 2-amino4,5,6,7,8,9-hexahydrocycloocta[b]thiophenes as
allosteric modulators of the A(1) adenosine receptor.
Bioorg Med Chem Lett, 2011. 21(12): p. 3704-3707
[PHARM]
Aydin, I., A. Dimitropoulos, S.H. Chen, C. Thomas,
and A. Roujeinikova, Purification, crystallization
and preliminary X-ray crystallographic analysis of
the putative Vibrio parahaemolyticus resuscitationpromoting factor YeaZ. ACTA Crystall F, 2011. F67(5):
p. 604-607 [BCH,MICRO]
Aydin, I., Y. Saijo-Hamano, K. Namba, C. Thomas,
and A. Roujeinikova, Structural Analysis of the
Essential Resuscitation Promoting Factor YeaZ
Suggests a Mechanism of Nucleotide Regulation
through Dimer Reorganization. PLoS One, 2011. 6(8):
p. e23245 [MICRO,BCH]
Bach, M., M. Larance, D.E. James, and G. Ramm,
The Serine/Threonine Kinase ULK1 is a target of
multiple phosphorylation events. Biochem J, 2011.
440(2): p. 283-291 [BCH,MMI]
Balamatsias, D., A.M. Kong, J.E. Waters, A.
Sriratana, R. Gurung, C.G. Bailey, J.E. Rasko,
T. Tiganis, S.L. Macaulay, and C.A. Mitchell,
Identification of P-Rex1 as a novel Rac1-guanine
nucleotide exchange factor (GEF) that promotes actin
remodelling and GLUT4 trafficking in adipocytes. J Biol
Chem, 2011. 286(50): p. 43229-43240 [BCH]
Bannam, T.L., X.X. Yan, P.F. Harrison, T. Seemann,
A.L. Keyburn, C. Stubenrauch, L.H. Weeramantri,
J.K. Cheung, B.A. McClane, J.D. Boyce, R.J.
Moore, and J.I. Rood, Necrotic enteritis-derived
Clostridium perfringens strain with three closely
related independently conjugative toxin and antibiotic
resistance plasmids. MBio, 2011. 2(5): p. e00190-11
[MICRO]
Becker, T., L.S. Wenz, V. Kruger, W. Lehmann, J.M.
Muller, L. Goroncy, N. Zufall, T. Lithgow, B. Guiard, A.
Chacinska, R. Wagner, C. Meisinger, and N. Pfanner,
The mitochondrial import protein Mim1 promotes
biogenesis of multispanning outer membrane proteins.
J Cell Biol, 2011. 194(3): p. 387-395 [BCH]
Beeman, S.C., M. Zhang, L. Gubhaju, T. Wu, J.F.
Bertram, D.H. Frakes, B.R. Cherry, and K.M. Bennett,
Measuring glomerular number and size in perfused
kidneys using MRI. Am J Physiol Renal Physiol, 2011.
300(6): p. F1454-F1457 [ANT]
Beltran, M.A., D.M. Paganin, K.K. Siu, A. Fouras, S.B.
Hooper, D.H. Reser, and M.J. Kitchen, Interfacespecific x-ray phase retrieval tomography of complex
biological organs. Phys Med Biol, 2011. 56(23): p.
7353-7369 [PHY]
Benziane, B., U. Widegren, S. Pirkmajer, J.
Henriksson, N.K. Stepto, and A.V. Chibalin, Effect
of exercise and training on phospholemman
phosphorylation in human skeletal muscle. Am J
Physiol Endocrinol Metab, 2011. 96(1): p. E48-E56
[PHY]
Berry, R., Z. Chen, J. McCluskey, and J. Rossjohn,
Insight into the basis of autonomous immunoreceptor
activation. Trends Immunol, 2011. 32(4): p. 165-170
[BCH]
Bertucci, M.C., J.M. Loose, E.M. Wallace, G. Jenkin,
and S.L. Miller, Anti-inflammatory therapy in an ovine
model of fetal hypoxia induced by single umbilical
artery ligation. Reprod Fertil Dev, 2011. 23(2): p. 346352 [PHY]
Bettaieb, A., S. Liu, Y. Xi, N. Nagata, K. Matsuo, I.
Matsuo, S. Chahed, J. Bakke, H. Keilhack, T. Tiganis,
and F.G. Haj, Differential regulation of endoplasmic
reticulum stress by protein tyrosine phosphatase 1B
and T cell protein tyrosine phosphatase. J Biol Chem,
2011. 286(11): p. 9225-9235 [BCH]
Bharadwaj, M., P. Illing, A. Theodossis, A.W. Purcell,
J. Rossjohn, and J. McCluskey, Drug Hypersensitivity
and Human Leukocyte Antigens of the Major
Histocompatibility Complex. Annu Rev Pharmacol
Toxicol, 2011. E-pub: p. 401-431 [BCH]
Bird, A.D., S.J. Flecknoe, K.H. Tan, P.F. Olsson, N.
Antony, T. Mantamadiotis, S.B. Hooper, and T.J.
Cole, cAMP Response Element Binding Protein Is
Required for Differentiation of Respiratory Epithelium
during Murine Development. PLoS One, 2011. 6(3): p.
e17843 [BCH]
Boerboom, D., J.F. Lafond, X. Zheng, E. Lapointe,
L. Mittaz, A. Boyer, M.A. Pritchard, F.J. Demayo, J.S.
Mort, R. Drolet, and J.S. Richards, Partially redundant
functions of Adamts1 and Adamts4 in the perinatal
development of the renal medulla. Dev Dyn, 2011.
240(7): p. 1806-1814 [BCH]
Borg, M.L., Z.B. Andrews, E.J. Duh, R. Zechner, P.J.
Meikle, and M.J. Watt, Pigment Epithelium-Derived
Factor Regulates Lipid Metabolism via Adipose
Triglyceride Lipase. Diabetes, 2011. 60(5): p. 14581466 [PHY]
Bosnyak, S., E. Jones, A. Christopoulos, M.I.
Aguilar, W. Thomas, and R. Widdop, Relative affinity
of angiotensin peptides and novel ligands at AT1 and
AT2 receptors. Clin Sci (Lond), 2011. 121(7): p. 297303 [PHARM,BCH]
Botte, C.Y., Y. Yamaryo-Botte, J. Janouskovec, T.
Rupasinghe, P.J. Keeling, P. Crellin, R. Coppel, E.
Marechal, M.J. McConville, and G.I. McFadden,
Identification of plant-like galactolipids in Chromera
velia, a photosynthetic relative of malaria parasites. J
Biol Chem, 2011. 286(34): p. 29893-29903 [MICRO]
Bottomley, S.P., The structural diversity in alpha(1)antitrypsin misfolding. EMBO Rep, 2011. 12(10): p.
983-984 [BCH]
Brait, V.H., J. Rivera, B.R. Broughton, S. Lee, G.R.
Drummond, and C.G. Sobey, Chemokine-related
gene expression in the brain following ischemic stroke:
No role for CXCR2 in outcome. Brain Res, 2011.
1372: p. 169-179 [PHARM]
Brennan, A.J., J. Chia, K.A. Browne, A. Ciccone, S.
Ellis, J.A. Lopez, O. Susanto, S. Verschoor, H. Yagita,
J.C. Whisstock, J.A. Trapani, and I. Voskoboinik,
Protection from endogenous perforin: glycans and the
C terminus regulate exocytic trafficking in cytotoxic
lymphocytes. Immunity, 2011. 34(6): p. 879-892
[BCH]
Brew, N., S.B. Hooper, B.J. Allison, M.J. Wallace, and
R. Harding, Injury and repair in the very immature lung
following brief mechanical ventilation. Am J Physiol
Lung Cell Mol Physiol, 2011. 301(6): p. L917-L926
[ANT]
Briggs, D.I. and Z.B. Andrews, Metabolic Status
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Li, and J.M. Carr, TNF-{alpha} stimulation of cells with
established dengue virus type 2 (DENV-2) infection
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Wiede, F., B.J. Shields, S.H. Chew, K. Kyparissoudis,
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Wilksch, J.J., J. Yang, A. Clements, J.L. Gabbe,
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Wun, K.S., G. Cameron, O. Patel, S.S. Pang, D.G.
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Xie, N., K. Huang, T. Zhang, Y. Lei, R. Liu, K. Wang,
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Xu, T.B., G.A. Eppel, G.A. Head, and R.G. Evans,
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Yallowitz, A.R., S.M. Hrycaj, K.M. Short, I.M. Smyth,
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Yan, Y., Y. Wang, J.K. Heath, E.C. Nice, and F.
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A. Masui, C. Wong, K.L. Loveland, and Y. Yoneda,
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Zhai, J., L.J. Waddington, T.J. Wooster, M.I. Aguilar,
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Zhai, J., T.J. Wooster, S.V. Hoffmann, T.H. Lee, M.A.
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Zhou, K., G. Zhi Sun, C.C. Bernard, G.A. Thouas,
D.R. Nisbet, and J.S. Forsythe, Optimizing interfacial
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Zhou, Z.D., C.H. Chan, Q.H. Ma, X.H. Xu, Z.C. Xiao,
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Zhu, J.Z., C.J. Millard, J.P. Ludeman, L.S. Simpson,
D.J. Clayton, R.J. Payne, T.S. Widlanski, and M.J.
Stone, Tyrosine Sulfation Influences the Chemokine
Binding Selectivity of Peptides Derived from
Chemokine Receptor CCR3. Biochemistry, 2011.
50(9): p. 1524-1534 [BCH]
Zinkernagel, M.S., P.G. McMenamin, J.V. Forrester,
and M.A. Degli-Esposti, T cell responses in
experimental viral retinitis: mechanisms, peculiarities
and implications for gene therapy with viral vectors.
Prog Retin Eye Res, 2011. 30(4): p. 275-284 [ANT]
Zohdi, V., M.J. Black, and J.T. Pearson, Elevated
vascular resistance and afterload reduce the cardiac
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Reviews
Drummond, G.R., S. Selemidis, K.K. Griendling, and
C.G. Sobey, Combating oxidative stress in vascular
disease: NADPH oxidases as therapeutic targets. Nat
Rev Drug Discov, 2011. 10(6): p. 453-471 [PHARM]
Fulcher, A.J. and D.A. Jans, Regulation of
nucleocytoplasmic trafficking of viral proteins: An
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2011. 1813(12): p. 2176-2190 [BCH]
Godfrey, D.I. and J. Rossjohn, New ways to turn on
NKT cells. J Exp Med, 2011. 208(6): p. 1121-1125
[BCH]
Gras, S., L. Kjer-Nielsen, Z. Chen, J. Rossjohn, and
J. McCluskey, The structural bases of direct T-cell
allorecognition: implications for T-cell-mediated
transplant rejection. Immunol Cell Biol, 2011. 89(3): p.
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Harper, M., A.D. Cox, B. Adler, and J.D. Boyce,
Pasteurella multocida lipopolysaccharide: The long
and the short of it. Vet Microbiol, 2011. 153(1-2): p.
109-115 [MICRO]
He, Z., A.J. Vingrys, J.A. Armitage, and B.V. Bui, The
role of blood pressure in glaucoma. Clin Exp Optom,
2011. 94(2): p. 133-149 [ANT]
Kennan, R.M., X. Han, C.J. Porter, and J.I. Rood,
The pathogenesis of ovine footrot. Vet Microbiol,
2011. 153(1-2): p. 59-66 [MICRO,BCH]
Koppers, A.J., T. Reddy, and M.K. O'Bryan, The
role of cysteine-rich secretory proteins in male fertility.
Asian J Androl, 2011. 13(1): p. 111-117 [ANT]
Kranich, J., K.M. Maslowski, and C.R. Mackay,
Commensal flora and the regulation of inflammatory
and autoimmune responses. Semin Immunol, 2011.
23(2): p. 139-145 [IMM-C]
Actis, G.C., F. Rosina, and I.R. Mackay, Inflammatory
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Expert Rev Gastroenterol Hepatol, 2011. 5(3): p. 401410 [BCH]
Lee, A.B., D. Nandurkar, M.E. Schneider-Kolsky,
M. Crossett, S.K. Seneviratne, J.D. Cameron, and
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Adler, B., M. Lo, T. Seemann, and G.L. Murray,
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Mijaljica, D., M. Prescott, and R.J. Devenish,
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Aitken, R.J. and A.J. Koppers, Apoptosis and DNA
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Quenault, T., T. Lithgow, and A. Traven, PUF
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Trends Cell Biol, 2011. 21(2): p. 104-112 [BCH]
Allwood, E.M., R.J. Devenish, M. Prescott, B. Adler,
and J.D. Boyce, Strategies for Intracellular Survival
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Selmi, C., C.L. Bowlus, M.E. Gershwin, and R.L.
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Andrews, Z.B., The extra-hypothalamic actions of
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Andrews, Z.B., Central mechanisms involved in the
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Archbold, J.K., J.U. Flanagan, H.A. Watkins, J.J.
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modification of secretin family G protein-coupled
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Baker, J.G., S.J. Hill, and R.J. Summers, Evolution
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p. 227-234 [PHARM]
Bertram, J.F., R.N. Douglas-Denton, B. Diouf, M.D.
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Campbell, B.E., P.R. Boag, A. Hofmann, C.
Cantacessi, C.K. Wang, P. Taylor, M. Hu, Z.U. Sindhu,
A. Loukas, P.W. Sternberg, and R.B. Gasser, Atypical
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Biotechnol Adv, 2011. 29(3): p. 338-350 [BCH]
Canals, M., P.M. Sexton, and A. Christopoulos,
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Shingu-Vazquez, M. and A. Traven, Mitochondria and
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10(11): p. 1376-1383 [BCH]
Song, J., H. Tan, S.E. Boyd, H. Shen, K. Mahmood,
G.I. Webb, T. Akutsu, J.C. Whisstock, and R.N. Pike,
Bioinformatic approaches for predicting substrates
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Spencer, S.J., M.A. Galic, and Q.J. Pittman, Neonatal
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Stewart, S.E., M.E. D'Angelo, and P.I. Bird,
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Tiganis, T., Reactive oxygen species and insulin
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Books, Book Chapters,
Electronic Books
and CD Roms
Bayliss, J., R. Stark, A. Reichenbach, and Z.B.
Andrews, Gut Hormones restrict neurodegeneration
in Parkinson's Disease, in Advanced Understanding of
Neurodegenerative Diseases, R.C.-C. Chang, Editor.
2011, InTech: Croatia. p. 269-284 [PHY]
Beilharz, T.H. and T. Preiss, Polyadenylation State
Microarray (PASTA) Analysis, in Methods Mol Biol
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Editors. 2011, Humana Press: USA. p. 133-148
[BCH]
Beinrohr, L., T.A. Murray-Rust, L. Dyksterhuis,
P. Zavodszky, P. Gal, R.N. Pike, and L.C.
Wijeyewickrema, Serpins and the complement
system, in Methods Enzymol, P. Bird and J.
Whisstock, Editors. 2011, Academic Press Elsevier
Inc: UK. p. 55-75 [BCH]
Black, M.J., M.R. Sutherland, and L. Gubhaju,
Effects of Preterm Birth on the Kidney, in Basic
Nephrology and Acute Kidney Injury, M. Sahay, Editor.
2011, InTech: India. p. 61-88 [ANT]
Chidgey, A.P., N. Seach, R. Lim, and R.L. Boyd,
Stem Cells and Regenerative Medicine - The Evolving
Story, in Stem Cell Technologies, S. Totey and K. Deb,
Editors. 2011, Tata McGraw-Hill Education Private
Limited: USA. p. 1-18 [MISCL]
Mackay, I.R., Gastrointestinal: Liver, in Systemic
Lupus Erythematosus, G.T. RG Lahita, JP Buyon, T
Koike, Editor. 2011, Academic Press (Elsevier): UK. p.
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Mijaljica, D., C.J. Rosado, R.J. Devenish, and M.
Prescott, Biosensors for monitoring autophagy, in
Biosensors - Emerging Materials and Applications, P.
Serra, Editor. 2011, InTech: Croatia. p. 383-400 [BCH]
Pearce, M.C. and L.D. Cabrita, Production of
Recombinant Serpins in Escherichia coli, in Methods
Enzymol, P. Bird and J. Whisstock, Editors. 2011,
Academic Press: USA. p. 13-28 [BCH]
Phan, J., N. Yamout, J. Schmidberger, S.P.
Bottomley, and A.M. Buckle, Refolding Your Protein
with a Little Help from REFOLD, in Methods Mol Biol,
K.B. AF Hill, SP Bottomley and R Cappai, Editor.
2011, Humana Press: UK. p. 45-57 [BCH]
Song, J., A.Y. Matthews, C.F. Reboul, D. Kaiserman,
R.N. Pike, P.I. Bird, and J.C. Whisstock, Predicting
serpin/protease interactions, in Methods Enzymol,
PI Bird and J. Whisstock, Editors. 2011, Academic
Press: USA. p. 237-273 [BCH]
Yongqing, T., J. Potempa, R.N. Pike, and L.C.
Wijeyewickrema, The lysine-specific gingipain
of porphyromonas gingivalis : importance to
pathogenicity and potential strategies for inhibition, in
Adv Exp Med Biol - Cystein Proteases of Pathogenic
Organisms, M.R.a.J. Dalton, Editor. 2011, Springer
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Dunstone, M.A. and J.C. Whisstock, Crystallography
of serpins and serpin complexes, in Methods Enzymol,
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Other publications
Furic, L., M. Livingstone, I. Topisirovic, and N.
Sonenberg, Actions of Insulin As a Survival and
Growth Factor: Akt, mTOR, and Regulation of
Translation, in Insulin Resistance and Cancer Epidemiology, Cellular and Molecular Mechanisms and
Clinical Implications, I. Fantus, Editor. 2011, Springer
Science + Business Media LLC: USA. p. 181-192
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Richards, M., J. Knox, B. Elliott, K. Mackin, D. Lyras,
L.J. Waring, and T.V. Riley, Severe infection with
Clostridium difficile PCR ribotype 027 acquired in
Melbourne, Australia. Med J Aust, 2011. 194(7): p.
369-371 [MICRO]
Grassinger, J. and S.K. Nilsson, Methods to analyze
the homing efficiency and spatial distribution of
hematopoietic stem and progenitor cells and their
relationship to the bone marrow endosteum and
vascular endothelium, in Methods Mol Biol - Stem Cell
Migration, M.-D. Filippi and H. Geiger, Editors. 2011,
Springer Science + Business Media, LLC 2011: USA.
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Cases
Clinical
Samarawickrema, N.A., S.N. Tabrizi, J. Hewavisenthi,
T. Leong, and S.M. Garland, Distribution of human
papillomavirus genotypes in archival cervical tissue
from women with cervical cancer in urban Sri Lanka.
Int J Gynaecol Obstet, 2011. 115(2): p. 180-182
[BCH]
Communications
Grigoryev, S. and S. McGowan, Isolation and
Characterization of the Nuclear Serpin MENT, in
Methods Enzymol, P. Bird and J. Whisstock, Editors.
2011, Academic Press: USA. p. 29-47 [BCH]
Brown, K.A., K.J. McInnes, K. Takagi, K. Ono, N.I.
Hunger, L. Wang, H. Sasano, and E.R. Simpson,
LKB1 expression is inhibited by estradiol-17beta
in MCF-7 cells. J Steroid Biochem Mol Biol, 2011.
127(3-5): p. 1-5 [PHY,BCH]
Ho, M.S., A. Fryga, and A.L. Laslett, Flow cytometric
analysis of human pluripotent stem cells, in Methods
Mol Biol, P. Schwartz and R. Wesselschmidt, Editors.
2011, Springer Science + Business Media, LLC: USA.
p. 221-230 [ANT]
Cronin, C., T.M. Edwards, and M.E. Gibbs, Role for
purinergic receptors in memory processing in young
chicks. Behav Brain Res, 2011. 223(2): p. 417-420
[ANT]
Horvath, A.J., B.G. Lu, R.N. Pike, and S.P. Bottomley,
Methods to measure the kinetics of protease inhibition
by serpins, in Methods Enzymol, P. Bird and J.
Whisstock, Editors. 2011, Academic Press USA. p.
223-235 [BCH]
Hou, X., D.H. Small, and M.I. Aguilar, Surface
plasmon resonance spectroscopy: a new lead in
studying the membrane binding of amyloidogenic
transthyretin, in Methods Mol Biol, K.B. AF Hill, SP
Bottomley, and R. Cappai, Editors. 2011, Springer
Science + Business Media, LLC: USA. p. 215-228
[BCH]
Kaiserman, D., C. Hitchen, V. Levina, S.P. Bottomley,
and P.I. Bird, Intracellular production of recombinant
serpins in yeast, in Methods Enzymol, P. Bird and J.
Whisstock, Editors. 2011, Academic Press: USA. p.
1-12 [BCH]
Kass, I., C.F. Reboul, and A.M. Buckle,
Computational methods for studying serpin
conformational change and structural plasticity, in
Methods Enzymol, P. Bird and J. Whisstock, Editors.
2011, Academic Press: USA. p. 295-323 [BCH]
Kouspou, M.M. and J.T. Price, Analysis of cellular
migration using a two-chamber methodology, in
Methods Mol Biol - Molecular Chaperones, S.
Calderwood and T. Prince, Editors. 2011, Springer
Science+business Media, LLC 2011: USA. p. 303-317
[BCH]
Elliott, D.A., S.R. Braam, K. Koutsis, E.S. Ng, R.
Jenny, E.L. Lagerqvist, C. Biben, T. Hatzistavrou, C.E.
Hirst, Q.C. Yu, R.J. Skelton, D. Ward-van Oostwaard,
S.M. Lim, O. Khammy, X. Li, S.M. Hawes, R.P.
Davis, A.L. Goulburn, R. Passier, O.W. Prall, J.M.
Haynes, C.W. Pouton, D.M. Kaye, C.L. Mummery,
A.G. Elefanty, and E.G. Stanley, NKX2-5eGFP/w
hESCs for isolation of human cardiac progenitors and
cardiomyocytes. Nat Methods, 2011. 8(12): p. 10371040 [MISCL]
Qi, T., K. Ly, D.R. Poyner, G. Christopoulos, P.M.
Sexton, and D.L. Hay, Structure-function analysis of
amino acid 74 of human RAMP1 and RAMP3 and its
role in peptide interactions with adrenomedullin and
calcitonin gene-related peptide receptors. Peptides,
2011. 32(5): p. 1060-1067 [PHARM]
Telwatte, S., K. Moore, A. Johnson, D. Tyssen, J.
Sterjovski, M. Aldunate, P.R. Gorry, P.A. Ramsland,
G.R. Lewis, J.R. Paull, S. Sonza, and G. Tachedjian,
Virucidal activity of the dendrimer microbicide
SPL7013 against HIV-1. Antiviral Res, 2011. 90(3): p.
195-199 [MICRO]
Verghese, E., J. Zhuang, D. Saiti, S.D. Ricardo, and
J.A. Deane, In vitro investigation of renal epithelial
injury suggests that primary cilium length is regulated
by hypoxia-inducible mechanisms. Cell Biol Int, 2011.
35(9): p. 909-913 [MISCL]
Conference Papers
Kamada, M., M. Hayashida, J. Song, and T. Akutsu,
Discriminative Random Field Approach to Prediction
of Protein Residue Contacts, in The 4th International
Conference on Computational Systems Biology
(ISB2010), X.-S.Z. L Chen, Y Wang, Editor. 2011,
IEEE: Zhuhai, China. p. 285-291 [BCH].
Wang, M., H.-B. Shen, T. Akutsu, and J. Song,
Predicting functional impact of single amino acid
polymorphisms by integrating sequence and structural
features, in The 4th International Conference on
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Chen, Y Wang, Editor. 2011, IEEE: Zhuhai, China.
p. 18-26 [BCH].
Xu, K.-J., F.-Y. Hu, J. Song, and X.-M. Zhao, Exploring
drug combinations in a drug-cocktail network, in 2011
IEEE Conference on Systems Biology (ISB2010),
X.-S.Z. L Chen, Y Wang, Editor. 2011, IEEE: Zhuhai,
China. p. 393-398 [BCH].
Editorials
Carter, G.P., M.M. Awad, M.L. Kelly, J.I. Rood, and
D. Lyras, TcdB or not TcdB: a tale of two Clostridium
difficile toxins. Future Microbiol, 2011. 6(2): p. 121-123
[MICRO]
Denton, K.M., The renin-angiotensin system: new
horizons. J Hypertens, 2011. 29(10): p. 1857-1858
[PHY]
Devenish, R.J., Autophagy and the evasion of
host defense: A new variation on the theme for
Burkholderia cepacia? Autophagy, 2011. 7(11) p.
1269-1270 [BCH]
Evans, R.G. and D.F. Su, Data presentation and use
of statistical tests in biomedical journals: can we reach
a consensus? Clin Exp Pharmacol Physiol, 2011.
38(5): p. 285-286 [PHY]
Kemp-Harper, B.K., Nitroxyl (HNO): a novel redox
signaling molecule. Antioxid Redox Signal, 2011.
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Should there be a national core curriculum for
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127
Research Staff Index
A
G
Gabriel, Dr Kip
P
Abud, Dr Helen 28
Adler, Professor Ben
53
Parkington, Associate Professor Helena
66
Pike, Professor Robert
52
Aguilar, Associate Professor Mibel
78
H
Andrews, Dr Zane
72
Harding, Professor Richard
31
Price, Dr John
18
Price, Dr Nicholas
Armitage, Dr James
28
Henry, Dr Belinda
67
73
Prescott, Dr Mark
83
39
Pritchard, Dr Melanie
35
J
R
Jans, Professor David
56
Rajan, Associate Professor Ramesh
67
Ricardo, Associate Professor Sharon
49
K
Risbridger, Professor Gail
19
Kett, Dr Michelle
22
Rood, Professor Julian
58
14
Rosa, Professor Marcello
65
Rossjohn, Professor Jamie
84
Roujeinikova, Associate Professor Anna
59
Hodgson, Professor Wayne
B
55
Bernard, Professor Claude 46
Bertram, Professsor John
29
Beddoe, Associate Professor Travis
78
Bird, Professor Phillip
52
Black, Associate Professor Mary Jane 29
Boag, Dr Peter 30
Borg, Dr Natalie 79
Bottomley, Professor Stephen 79
Boyce, Dr John 53
Lackmann, Associate Professor Martin
15
Boyd, Professor Richard 47
Lang, Dr Richard
66
S
Buckle, Associate Professor Ashley
80
Lawen, Dr Alfons
14
Schneider-Kolsky, Dr Michal
61
Burman, Dr Kathleen
64
31
Sexton, Professor Patrick
38
Bunnett, Professor Nigel
38
56
Smith, Professor Ian
23
Loveland, Professor Kate
32
Smith, Dr Jeremy T 68
Lyras, Dr Dena
57
C
Chidgey, Associate Professor Ann Christopoulos, Professor Arthur Kwok-Schuelein, Dr Terry
L
Li, Dr Jinhua
Lithgow, Professor Trevor
Smyth, Dr Ian
35
47
Sobey, Associate Professor Chris
24
38
Spencer, Dr Sarah J
74
Stanley, Professor Ed
48
Summers, Professor Roger
38
Clarke, Professor Iain 64
Clements, Dr Craig Cole, Associate Professor Timothy M
Mackay, Professor Charles
42
80
McGowan, Dr Sheena
82
30
McMenamin, Professor Paul 33
Coleman, Dr Harold 66
Meeusen, Professor Els
57
T
Cooke, Professor Brian 54
Mitchell, Professor Christina
16
Tare, Dr Marianne
66
Coulibaly, Dr Fasseli 81
Tiganis, Professor Tony
18
Cowley, Professor Michael 72
Tilbrook, Professor Alan
68
Traven, Dr Ana
59
D
N
Nagley, Professor Phillip
17
Netter, Associate Professor Hans
58
Nice, Professor Ed
17
W
Davies, Professor John
54
Denton, Associate Professor Kate
22
Watt, Associate Professor Matthew
74
Devenish, Professor Rod
55
Whisstock, Professor James
85
Drummond, Dr Grant
24
Widdop, Professor Robert
25
Dunstone, Dr Michelle 82
Wilce, Associate Professor Jackie
83
Wilce, Professor Matthew
83
E
O
O’Bryan, Professor Moira
34
Oldfield, Professor Brian
73
Elefanty, Professor Andrew
48
Y
Elliott, Professor David
49
Yu, Dr Di
Evans, Associate Professor Roger
22
43
Further information
School of Biomedical Sciences
Building 77
Monash University
Clayton, VIC 3800
Australia
Telephone: +61 3 9902 9407
Email: [email protected]
twitter.com/Monash_FMNHS
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Monash University reserves the right to alter information, procedures, fees and regulations contained in this document.
Please check the Monash University website for updates (www.monash.edu). All information reflects prescriptions,
policy and practice in force at time of publication. Published May 2012. MMS341041