Unravelling animal African trypanosomiasis: starve the parasite, feed the world

Of the 7 billion people alive today, around 20% (1.3 billion people) are affected by parasitic diseases. An estimated 1.5 million people die annually, and 110 million disability-adjusted life years (DALYs) are lost to them. Because of their chronic and debilitating nature (which keeps sufferers from being able to work, study or care for their families), parasitic diseases are the most common afflictions of the worlds poor, and a major restriction on economic development. This project aims to unravel the mechanics of parasite infection and thereby to expose avenues for therapeutic intervention. We focus our efforts on African trypanosomes: lethal parasites transmitted by tsetse fly bite, that cause sleeping sickness in some of the poorest countries of sub-Saharan Africa. The host-parasite interface: African trypanosomes parasitize the human bloodstream in an exclusive extracellular form: in the full view of the host immune system. Cell surface structure and composition is key to the parasite's strategy of immune evasion, survival and disease transmission. However, very little is known about the molecules that reside at this interface, how they get there, and which ones are essential to the parasite's success. This severely hampers the development of drugs or vaccines against human African trypanosomiasis and related parasitic diseases. Work in the lab takes innovative approaches to elucidate parasite cell membrane function, structure, molecular composition and evolution. Tom's project in particular will revolve around cell surface architecture and protein/lipid sorting mechanisms of immune evasion in African trypanosomiasis. The availability of a surface membrane proteome for the bloodstream form of Trypanosoma brucei allowed Tom's project to start with investigation of transport mechanisms that direct surface proteins to the host-parasite interface. Currently Tom cultures and genetically modifies parasites under an ACDP Class II* pathogen containment facility. He uses molecular biology techniques to tag specific genes, and use biochemical methods to assess successful transfection and cellular location. Tagged protein analysis is assayed by fluorescence. In doing so, it is hoped that he will identify critical cell membrane molecules and sorting pathways at the host-parasite interface for human African trypanosomiasis. It is predicted that surface membrane constituents identified will include potential drug targets that are i) different from the host, ii) exposed to the extracellular space, and iii) provide vital function. The project also aims to test candidate molecules for potential in vaccine development.