Molecular mechanisms mediating immune evasion in African trypanosomes.

African trypanosomes—single-celled parasites that cause sleeping sickness—switch their surface coats like a fugitive changing disguises, and this project aims to expose exactly how they do it. The parasite evades the human immune system by periodically swapping out a dense protein layer called VSG on its surface, allowing it to stay one step ahead of antibody attacks. Researchers already know that only one VSG gene is active at a time, but the molecular machinery that controls this strict on/off switching—and that ensures the coat is properly made before the cell divides—remains poorly understood. This project will dissect the roles of specific proteins (TbISWI, NLP, FACT, NAP1, and histone H1) in regulating VSG expression, and investigate how the parasite senses whether VSG synthesis is complete before it commits to cell division. If successful, this fundamental science will reveal the basic biology of a major human pathogen. Understanding these immune evasion mechanisms could eventually point toward new drug targets—for example, by disrupting the coat-switching process or by triggering the cell-cycle checkpoint that kills the parasite when VSG production fails. There is no immediate practical application, but similar work on parasite surface proteins has historically opened routes to vaccines and therapies for diseases like malaria.