Functional Glycomics of the African Sleeping Sickness Parasite Trypanosoma brucei
Lead Research Organisation:
University of Dundee
Department Name: College of Life Sciences
Abstract
Mike Ferguson and Geoff Barton are frequently interviewed about drug development against tropical diseases, post-genomics and bioinformatics by local and national newspapers, radio and TV. They also give frequent presentations to school students, Rotary Clubs and other organisations on their research and on the importance of Biomedical Research in a local, national and international context.
Technical Summary
The African trypanosome Trypanosoma brucei causes human African sleeping sickness and the cattle disease nagana. The human and socio-economic impacts of these diseases are considerable; WHO estimates that 300,000-500,000 people are currently infected and millions are at risk. The available drugs for humans (eg. the arsenical melarsaprol) are inadequate, toxic and difficult to administer. Work by ourselves and others has highlighted the importance of protein glycosylation in trypanosome survival and infectivity. The proposed programme aims to:
1. Complete the Trypanosome Structural Glycome.
2. Identify genes, particularly glycosyltransferases, involved in glycoconjugate biosynthesis.
3. Experimentally define the precise functions of selected genes and distribute this information via the T.brucei GeneDB database and via protein DAS and similar technologies.
4. In conjunction with our experimental work, develop improved predictors of glycosyltransferase specificity and for T.brucei-specific signal peptides and N-linked, O-linked and P-linked glycosylation sites.
5. Identify glycosyltransferase genes that are essential to the disease-causing bloodstream form of the parasite and express appropriate domains thereof for X-ray crystallography.
6. Provide information and methodologies on protein glycosylation and enzyme function prediction that will be of general significance to the wider biochemistry, cell biology and bioinformatics communities.
1. Complete the Trypanosome Structural Glycome.
2. Identify genes, particularly glycosyltransferases, involved in glycoconjugate biosynthesis.
3. Experimentally define the precise functions of selected genes and distribute this information via the T.brucei GeneDB database and via protein DAS and similar technologies.
4. In conjunction with our experimental work, develop improved predictors of glycosyltransferase specificity and for T.brucei-specific signal peptides and N-linked, O-linked and P-linked glycosylation sites.
5. Identify glycosyltransferase genes that are essential to the disease-causing bloodstream form of the parasite and express appropriate domains thereof for X-ray crystallography.
6. Provide information and methodologies on protein glycosylation and enzyme function prediction that will be of general significance to the wider biochemistry, cell biology and bioinformatics communities.