The Cell Biology of Parasitism in Trypanosoma brucei: Insights and Drug Targets from Genomic Approaches?

The African trypanosome, Trypanosoma brucei exhibits a complex, digenetic life cycle that alternates between the tsetse fly vector and the mammalian host. The life cycle is characterised by a complex series of cell type differentiations and variations in metabolism. In addition the trypanosome exhibits a particular cell biology that has become adapted for its role as a parasite. This article places some of these areas in a frame-work that considers the role of cellular processes in parasitism. I rehearse some conclusions from recent studies and provide hyphotheses and suggestions for future work. Areas debated include: cell surface protein expression, cell differentiation, endomembrane trafficking and protein targeting, the cytoskeleton,flagellum functions in motility, attachment and plasma membrane differentiation, organelle specialisations, control of cell cycle, parasite / host, parasite / parasite and parasite / vector interactions. The review also focusses on the likely impact of the genome project and reverse genetics in providing greater insight to these cellular processes and how, if coordinated with some élan by scientists and funding agencies, this may provide novel targets for future drug development.