Abstract

The African trypanosome Trypanosoma brucei is a single-celled parasite causing African Sleeping Sickness in subSaharan Africa. Trypanosomes multiply extracellularly in the blood, where they are exposed to continuous immune attack. As a consequence, they have developed a highly sophisticated strategy of antigenic variation of a protective Variant Surface Glycoprotein (VSG) coat allowing them to avoid erradication by host antibodies. An individual trypanosome has up to 2000 different VSG genes, of which one is expressed at a time in a strictly monoallelic fashion from one of about fifteen VSG expression site transcription units. We are trying to understand how the mutually exclusive expression of these different VSG genes is controlled. We are currently investigating the role of chromatin remodeling in VSG expression site control. In addition, we are investigating the role of the protective VSG coat itself. We have discovered that VSG synthesis is monitored during the T. brucei cell cycle, and that blocking its synthesis triggers a highly precise cell cycle arrest. This argues that VSG synthesis is part of a protective cellular checkpoint. Hopefullly, these investigations will help us understand what makes African trypanosomes such successful extracellular pathogens.