Dissecting the molecular basis of single gene choice in African trypanosomes

Several pathogens, including African trypanosomes, which are responsible for high mortality among some of the world?s poorest populations, undergo antigenic variation in order to evade the host immune response. They possess large families of genes that encode for surface exposed antigens, which they express in a monogenic fashion and are able to shift. The ability to express a single antigen at a time is critical for immune evasion. However, the machinery and mechanisms underpinning monogenic-expression remained mysterious for decades. I recently identified the protein-complex that sustains monogenic-expression of surface antigens in trypanosomes, providing a unique opportunity to further our knowledge of this complex process. I will apply a wide range of biochemical, imaging and genetic approaches to investigate the function of this protein-complex and identify other relevant factors. Antigenic variation is a sophisticated virulence mechanism that has greatly challenged vaccine development against several pathogens; its molecular understanding is therefore invaluable.