Why trypanosomes swim, how they swim
and why that is important
Niko Heddergott
Eric Stellamanns
Thomas Pfohl
Markus Engstler
.....and why that is important
.....and why that is important
Surgeon General
Sir David Bruce
Robert Koch
Albert Schweitzer
36 countries
60,000,000
500,000
60,000
Neglected
Poverty
War
Destruction
Migration
Banishment
Help
Hope
Chances
Diagnostics
Treatment
Therapy
1917
2007
100 years of research
“Antigenic variation makes VSG drug development a nonstarter.”
Trypanosomes /cu mm (µl) blood
Michael A. J. Ferguson (2000), PNAS 97, 10673
Ross and Thomson, 1910
(Proc. Royal. Soc. London 82: 411-415)
Days from probable time of infection
“Antigenic variation makes VSG drug development a nonstarter.”
Trypanosomes /cu mm (µl) blood
Michael A. J. Ferguson (2000), PNAS 97, 10673
Ross and Thomson, 1910
(Proc. Royal. Soc. London 82: 411-415)
Days from probable time of infection
“Antigenic variation makes VSG drug development a nonstarter.”
Trypanosomes /cu mm (µl) blood
Michael A. J. Ferguson (2000), PNAS 97, 10673
Ross and Thomson, 1910
(Proc. Royal. Soc. London 82: 411-415)
Days from probable time of infection
“Antigenic variation makes VSG drug development a nonstarter.”
Trypanosomes /cu mm (µl) blood
Michael A. J. Ferguson (2000), PNAS 97, 10673
Ross and Thomson, 1910
(Proc. Royal. Soc. London 82: 411-415)
Days from probable time of infection
Trypanosomes /cu mm (µl) blood
How do trypanosomes survive in the face of
raising antibody concentrations?
Ross and Thomson, 1910
(Proc. Royal. Soc. London 82: 411-415)
Days from probable time of infection
Trypanosomes /cu mm (µl) blood
How do trypanosomes survive in the face of
raising antibody concentrations?
Ross and Thomson, 1910
(Proc. Royal. Soc. London 82: 411-415)
Days from probable time of infection
Trypanosomes remove host antibodies from their cell surface
Directional movement
+ localized endocytosis
direction of swimming
dnai1 RNAi
direction of swimming
DNAI1 = dynein arm intermediate chain
That’s why trypanosomes swim...
Goals for SPP 1207
Goals for SPP 1207
Goals and Achievements:
Proposed
Biochemical and genetic manipulation
of the plasma membrane
Done
First Funding Period
In progress
Not started
Waived
Goals and Achievements:
Proposed
Done
First Funding Period
In progress
Not started
Biochemical and genetic manipulation
of the plasma membrane
Paul Englund wrote on April 2, 2007:
“So it looks like it will not be feasible to do the
experiments that you want to do unless we can figure
out a way to keep the cells alive when the ELO
pathway is inactivated.”
Waived
Goals and Achievements:
Proposed
Biochemical and genetic manipulation
of the plasma membrane
Genetic manipulation of the variant
surface glycoprotein
Done
First Funding Period
In progress
Not started
Waived
Goals and Achievements:
Proposed
Biochemical and genetic manipulation
of the plasma membrane
Genetic manipulation of the variant
surface glycoprotein
MITat1.2
Done
First Funding Period
In progress
Not started
Waived
Goals and Achievements:
Proposed
Done
First Funding Period
In progress
Biochemical and genetic manipulation
of the plasma membrane
Genetic manipulation of the variant
surface glycoprotein
MITat1.2
MITat1.2-lipoyl
Not started
Waived
Goals and Achievements:
Proposed
Biochemical and genetic manipulation
of the plasma membrane
Genetic manipulation of the variant
surface glycoprotein
Generation of mosaic surface coats
Done
First Funding Period
In progress
Not started
Waived
Goals and Achievements:
Proposed
Done
First Funding Period
In progress
Not started
Biochemical and genetic manipulation
of the plasma membrane
Genetic manipulation of the variant
surface glycoprotein
Generation of mosaic surface coats
Genetic manipulation of the GPIanchor
VSG:GPI
VSG:TM
VSG:TM
Waived
Goals and Achievements:
Proposed
Biochemical and genetic manipulation
of the plasma membrane
Genetic manipulation of the variant
surface glycoprotein
Generation of mosaic surface coats
Genetic manipulation of the GPIanchor
Immobilization of live trypanosomes
Done
First Funding Period
In progress
Not started
Waived
Goals and Achievements:
Proposed
Biochemical and genetic manipulation
of the plasma membrane
Genetic manipulation of the variant
surface glycoprotein
Generation of mosaic surface coats
Genetic manipulation of the GPIanchor
Immobilization of live trypanosomes
Cell surface clearance of host
complement
Done
First Funding Period
In progress
Not started
Waived
Goals and Achievements:
Proposed
Biochemical and genetic manipulation
of the plasma membrane
Genetic manipulation of the variant
surface glycoprotein
Generation of mosaic surface coats
Genetic manipulation of the GPIanchor
Immobilization of live trypanosomes
Cell surface clearance of host
complement
Advanced flicker spectroscopy
Done
First Funding Period
In progress
Not started
Waived
Goals and Achievements:
Proposed
Biochemical and genetic manipulation
of the plasma membrane
Genetic manipulation of the variant
surface glycoprotein
Generation of mosaic surface coats
Genetic manipulation of the GPIanchor
Immobilization of live trypanosomes
Cell surface clearance of host
complement
Advanced flicker spectroscopy
Measurement of cell surface protein
movement under flow conditions
Done
First Funding Period
In progress
Not started
Waived
Goals and Achievements:
Proposed
Biochemical and genetic manipulation
of the plasma membrane
Genetic manipulation of the variant
surface glycoprotein
Generation of mosaic surface coats
Genetic manipulation of the GPIanchor
Immobilization of live trypanosomes
Cell surface clearance of host
complement
Advanced flicker spectroscopy
Measurement of cell surface protein
movement under flow conditions
Analysis and simulation of motility in
microfluidic devices
Done
First Funding Period
In progress
Not started
Waived
WORK IN
PROGRESS
WORK IN
PROGRESS
EVOLUTION