The molecular control of antigenic variation in Trypanosoma brucei

The African trypanosome, Trypanosoma brucei, is a protozoan that causes sleeping sickness in humans and N'gana in livestock. These flagellated parasites are directly exposed to immune defences as they circulate in the mammalian host bloodstream but they maintain persistent infections by undergoing antigenic variation. Central to this process is mono-allelic transcription and switching of the expressed variant-surface glycoprotein (VSG) gene which encodes the vast majority of their dense surface coat. The active telomeric VSG is transcribed by RNA polymerase I in an 'expression site body' (ESB) while transcription attenuation occurs at 'inactive' telomeres. Here, I review what is known about the molecular mechanisms involved in achieving antigenic variation and outline how we intend to exploit genome sequence and new tools, particularly RNA interference, to identify and characterise factors required for VSG regulation.