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Department of Gene-cs, Microbiology and Toxicology 15 research groups (100 people, incl 4.5 TA staff) 38 PhD students Department board Head of department: Dag Jenssen Deputy head: Ann-­‐Beth Jonsson Research groups Administra-on Graduate studies: Elisabeth Haggård Undergraduate studies: Margareta Ohné Department of Gene-cs, Microbiology and Toxicology Microbiology Toxicology Gene-cs Ann-­‐Beth Jonsson (presents) Hong Sjölinder Helena Aro Leif Isaksson Håkan Steiner Dag Jenssen (presents) Andrzej Wojcik Mats Harms-­‐Ringdahl Ulf Rannug Thomas Helleday Per Palsböll (presents) Mary Hunt Ingrid Faye Elisabeth Haggård Anders Nilsson Microbiology research Neutophil hunting a bacterium
Ann-­‐Beth Jonsson Helena Aro Hong Sjölinder Leif Isaksson Håkan Steiner Cellular Microbiology -­‐ Interac-on with host cells Molecular infec-on biology: pathogenic bacteria and host cells. Ann-­‐Beth Jonsson group Research (1) Interac-on between microbes and host cells and -ssue. 1. 3. 4. 5. 6. Receptor-­‐ligand interac-ons. Cell signalling. An-microbial pep-des, Natural immunity. New targets for drugs. Proteomics and microarrays. Intracellular survival and passage. Methods:
Cell infecXon In vivo: mice, pigs Flow cytometry Immunoblots Microarrays/qPCR Cloning Expression Live cell microscopy Cytokine expression Ann-­‐Beth Jonsson group Research (2)
In vivo biophotonic imaging i.v. infec-on Control CD46
Experimental model systems. 1. 3. 3. CD46 transgenic mice. Germ-­‐free mice. TLR knock-­‐out mice. Day 1
Future treatments and vaccines. 1. 2. Test of vaccines. Novel treatments. . Day 3
Biophysics. 1. 2. Models of biological systems. Experimental data. Pilus retract
extend
OM
PilT
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Live animals Real-­‐-me Major funding: Swedish Research Council (M) Torsten och Ragnar Söderbergs S:;else Swedish Research Council (NT) Swedish Research Council (KFI) Swedish Cancer Society Members 2010: Katarina Vielfort, PhD student Niklas Söderholm, PhD student Linda Weyler, PhD student Sonja Löfmark, postdoc Nele de Klerk, project Eleonora Reginato, project Laura Spelmink, project The role of the growth factor Amphiregulin in bacterial infecXon Bacterial adhesion to the uropod of human neutrophils Funding: Swedish Medical Research Council (Vetenskapsrådet) Swedish Society for Medicin (Svenska Läkarsällskapet) Åke Wibergs sXcelse Magnus Bergwalls SXcelse SXcelsen Lars Hiertas Minne Harald Jeanssons SXcelse P. och A. Hedlunds SXcelse Cell cycle regulaXon during bacterial colonisaXon The interacXon between our normal flora and pathogenic bacteria Helena Aro group INTERPLAY L. gasseri
L. crispatus
CD46 and Ezrin localisaXon in human neutrophils ADHERENCE COMPETITION 30 min
(2&3$4&
p53 protein levels 5+-./0.1&
15 min
*+,+-./0.1&
C
NEUTROPHIL RECRUITMENT BACTERIAL ADHESION 1
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0.5
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0
Uninfected
Bacterial adherence Infected
DNA damage and repair Bacteria can control host cell cycle progression Hong Sjölinder group Molecular mechanisms of bacterial meningitis Thyroid hormones control sepsis ColonizaXon factors of bacteria 100
+T4
control
75
50
25
0
0
1
2
Days
3
4
Hong Sjölinder group"
Ongoing projects Group members!
1. Impact of neuro-endocrine
system on immuno-regulation
during sepsis!
2. Identification of novel virulence
"
factors that are essential for !
bacterial colonization and sepsis !
development !
3. Elucidation of novel vaccine "
candidates against disease!
Funding!
 The Swedish science council  Tore Nilsons S:;else  Harald Jeanssons S:;elser  Åke Wiberg S:;else  S:;elsen Anna Brita och Bo Castegrens Minne  S:;elsen Lars Hiertas Minne  Magn. Bergvalls S:;else  S:;elsen Goljes Minne Leif Isaksson group Control of bacterial gene expression at the transla3onal level Two lines of research: 1. Basic studies of the translaXon machinery. 2. ApplicaXons towards industry. Since the the plasmid is small no burden on cellular growth rate can be seen during growth in either minimal or rich media. There is 100% stability of the plasmid in the absence of any external selec-on acer more than 100 genera-ons of growth. Håkan Steiner group Innate immunity genes conserved from insects to man Without an armour of defense reacXons, any organism would perish from the mere growth of harmless microbes, as microbes colonize all living mafer. A rapid innate immune system can stop the growth of these microbes. Insects rely solely on such innate responses. The immune system must first recognize the invading microbe as foreign to set the innate defense in moXon. We are studying the nature of the interacXon between the microbial signature molecules and their receptors. In insects, receptors that recognize pepXdoglycan seem to be of outmost importance for the recogniXon of bacteria. We have also found that some members of this family of pepXdoglycan recogniXon proteins (PGRPs) are enzymes cleaving pepXdoglycan into pieces that do not sXmulate the immune system. Thus proteins belonging to the same family are either posiXve or negaXve regulators of innate immunity. Håkan Steiner group Characteriza*on and analysis of PGRPs (Pep*doglycan Recogni*on Proteins)