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Compositional and functional analysis of plasma membrane components of African trypanosomes

English title Compositional and functional analysis of plasma membrane components of African trypanosomes
Applicant Bütikofer Peter
Number 103695
Funding scheme Project funding (Div. I-III)
Research institution Institut für Biochemie und Molekulare Medizin Universität Bern
Institution of higher education University of Berne - BE
Main discipline Biochemistry
Start/End 01.05.2004 - 30.06.2007
Approved amount 248'300.00
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Keywords (6)

trypanosomes; surface glycoproteins; phosphorylation; kinase; GPI; phospholipids

Lay Summary (English)

Lead
Lay summary
Trypanosoma brucei and Trypanosoma congolense are the causative agents oftrypanosomiasis in domestic animals in Africa and have a major impact oneconomy and human development in the affected areas. The life cycles ofthe parasites are characterised by a succession of different forms adaptedto the different environments in the mammalian host and the insect vector.Glycosylphosphatidylinositol (GPI)-anchored glycoconjugates on the surfaceof T. brucei and T. congolense play crucial roles in parasite infectivityand survival.
Recent work has shown that the surface of most insect form trypanosomesis not covered by an invariant protein coat as previously thought but by amixture of complex glycosylated, GPI-anchored molecules that changesbetween the different life cycle stages in the tsetse fly. Our aim is tofurther characterise some of these surface molecules with regard to theirposttranslational modifications and expression profiles in procyclic(insect form) trypanosomes. The studies are based on our recentobservation that GPEET procyclin in T. brucei is heavily phosphorylated inthe pentapeptide repeat, which was unexpected since phosphorylatedproteins are generally believed to occur intracellularly, and we willattempt to identify and purify the kinase responsible for thismodification. In addition, we plan to characterise a novel abundantsurface protein in T. congolense and study its expression during flypassage. The regulated expression of surface coat molecules in T.congolense procyclic forms has only recently been reported and mayrepresent a key event in the life cycle progression of this economicallyimportant parasite. Finally, we will perform detailed phospholipidanalyses on T. brucei and T. congolense membranes to study the role ofmembrane lipids in trypanosome biology. This area of research has largelybeen neglected in the past but may harbour great potential for drugdevelopment since recent reports have shown that lipid metabolic pathwaysof protozoan parasites differ considerably from those of their mammalianhosts.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
116627 Analysis of novel biosynthetic pathways in trypanosoma brucei: ethanolamine incorporation into proteins and lipids 01.07.2007 Project funding (Div. I-III)
65056 Phosphorylation and function of surface proteins in African trypanosomes 01.10.2002 Project funding (Div. I-III)

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