The goal of this project is to study the surface glycoproteins of the African trypanosome, Trypanosoma brucei. VSG, the major surface protein of bloodstream form parasites, protects subsurface structures from recognition by the host immune system. Switching expression from one VSG to another (antigenic variation) allows the parasite to survive in the host's bloodstream. PARP (procyclic acidic repetitive protein) is an unusual protein which overs the surface of the insect form of T. brucei. Our studies focus mainly on the glycosyl groups of these proteins, with most studies on the GPI anchor of VSG. Since myristate is an important component of the VSG anchor, the first specific aim will be to study the mechanism by which myristate is taken up by the cell and processed. This is a problem for the parasite, as it cannot synthesize myristate and it lives in an environment where this fatty acid is in low concentration. In these studies we will purify and characterize myristoyl-CoA synthases and we shall look for myristate transporters and binding proteins. We shall use biochemical approaches as well as yeast genetics to find these proteins or their genes. The second specific aim will be to study GPI biosynthesis and catabolism, with most emphasis placed on the mechanism of GPI myristoylation in bloodstream forms. In the third specific aim we will characterize T. brucei glycosylation mutants. We have already isolated mutants of the procyclic stage of T. brucei, which have an altered PARP, and we are studying whether the mutations affect N-linked glycosylation or the GPI structure. We will attempt to clone the mutant gene by functional complementation
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| Hu, Rong; Mukhina, Galina L; Lee, Soo Hee et al. (2009) Silencing of genes required for glycosylphosphatidylinositol anchor biosynthesis in Burkitt lymphoma. Exp Hematol 37:423-434.e2 |
| Guler, Jennifer L; Kriegova, Eva; Smith, Terry K et al. (2008) Mitochondrial fatty acid synthesis is required for normal mitochondrial morphology and function in Trypanosoma brucei. Mol Microbiol 67:1125-42 |
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| Acosta-Serrano, Alvaro; O'Rear, Jessica; Quellhorst, George et al. (2004) Defects in the N-linked oligosaccharide biosynthetic pathway in a Trypanosoma brucei glycosylation mutant. Eukaryot Cell 3:255-63 |
| Jiang, David W; Werbovetz, Karl A; Varadhachary, Atul et al. (2004) Purification and identification of a fatty acyl-CoA synthetase from Trypanosoma brucei. Mol Biochem Parasitol 135:149-52 |
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