Why trypanosomes swim, how they swim and why that is important
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
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