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Analysis of novel biosynthetic pathways in trypanosoma brucei: ethanolamine incorporation into proteins and lipids

English title Analysis of novel biosynthetic pathways in trypanosoma brucei: ethanolamine incorporation into proteins and lipids
Applicant Bütikofer Peter
Number 116627
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 01.07.2007 - 31.07.2010
Approved amount 297'505.00
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Lay Summary (English)

Lay summary
African trypanosomes are protozoan parasites causing human African sleeping sickness and a related disease, called Nagana, in animals. These diseases have a major impact on human and animal health by severely affecting social and economic development among the poorest, mostly rural, populations in sub-Saharan Africa. During their complex life cycles, Trypanosoma brucei and Trypanosoma congolense alternate between the mammalian bloodstream and the insect host, the tsetse fly. Interestingly, research on trypanosomes has led to the discovery of several important biological phenomena, such as RNA editing, trans-splicing, GPI-anchoring and antigenic variation, which were subsequently found to occur in other eukaryotic organisms as well.Anchoring of proteins to membranes via glycosylphosphatidylinositol (GPI) is responsible for the attachment of millions of copies per cell of variant surface glycoproteins or procyclins in bloodstream or insect (procyclic) form trypanosomes, respectively. In the past, we have discovered several novel GPI-anchored surface molecules in T. brucei and T. congolense procyclic forms, analysed some of their posttranslational modifications, and studied their expression in cultured parasites and during tsetse fly transmission. We plan to continue this work and focus on the detailed characterisation of the carbohydrate and lipid modifications of two novel abundant GPI-anchored molecules in T. congolense procyclic forms.In the second - and major - part of the proposal, we are studying the biosynthesis, attachment, and functional significance of a rare protein modification. Such modifications often regulate the biological function(s) of a protein, its distribution within a cell, and interactions with partner molecules. It has been shown that eukaryotic elongation factor 1A (eEF1A) from mammalian cells and plants is modified with ethanolamine phosphoglycerol (EPG). However, nothing is known about the sequence requirement for EPG attachment, its pathway of synthesis, or functional significance. For the first time ever, we plan to address these questions using T. brucei as a model system. The results from our studies will delineate a novel pathway for protein modification and, hopefully, shed light on its functional importance for eEF1A, or other proteins. In addition, we are studying the metabolism of phospholipids in trypanosomes, an area of research that has received little attention in the past, but is currently investigated as potential drug target.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants


Associated projects

Number Title Start Funding scheme
103695 Compositional and functional analysis of plasma membrane components of African trypanosomes 01.05.2004 Project funding (Div. I-III)
130815 Novel biosynthetic pathways in Trypanosoma brucei: Biosynthesis of phospholipids and modification of eEF1A 01.08.2010 Project funding (Div. I-III)