A systems approach for understanding cell surface dynamics in trypanosomes

Infectious organisms exploit many varied approaches to surviving within their hosts, but one of the more spectacular and successful is antigenic variation. This process involves the constant alteration of the surface so that the host is unable to mount a successful immune response. In African people, this mechanism has become extremely sophisticated and relies on a superabundant surface protein. How this surface is maintained and how other proteins are also maintained at the surface, is not completely understood. Recent advances have begun to characterise the major players and mechanisms involved, and new and maturing technologies are now available that allow a detailed dissection of this process in a more holistic manner.

I propose a system-wide approach to understanding the roles of surface molecules in trypanosomes and how the surface is maintained. By exploiting methods that allow sampling of the entire trypanosome cell, this will allow an integrated, unbiased and comprehensive understanding of the roles of various proteins in maintaining surface composition. The combined outcomes will identify mechanisms that are unique to the parasite, those that represent vulnerable processes and also insights into therapeutic mechanisms.