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Functional genomics relating to the biosynthesis of trypanosome glycoconjugates


The African trypanosome Trypanosoma brucei causes African sleeping sickness and the cattle disease nagana. The human and socio-economic impact of these diseases is considerable. The available drugs for humans are inadequate and difficult to administer. Parasites are very dependent on glycoconjugates for their survival and infectivity. The main goal of this project is to determine the function of genes involved in galactose-containing glycoconjugate biosynthesis and processing in T. brucei.

The emerging T. bruce i genome will be systematically mined, and the candidate genes classified in different glycosyltransferase (GT) groups. Representative examples of these putative GTs will be experimentally examined by inducible RNAi knock-downs, by gene knockout, or by construction of tetracycline-inducible conditional null mutants. Mutant cells will be assessed for growth in vitro and for infectivity in vivo. Moreover, mutant cells will be bio-chemically phenotyped in both the blood stream and procyclic lifecycle forms of the parasite. In this way, we should be able to assign precise functions to genes and thus, identify sequence motifs/patterns that discriminate between different families of parasite enzymes.

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