RNA-based mechanisms in VSG allelic exclusion (360G-Wellcome-203816_Z_16_A)

Parasites like African trypanosomes cause diseases in animals and humans and depend upon the expression of a uniform cell surface coat that can switch to evade the host immune response. This is achieved by switching genes on and off in a process known as antigenic variation. Work in the Horn lab recently revealed a protein that controls this process. The current model indicates that the protein can bind to a specific DNA sequence and drive coat production. The protein can then carry a message to other similar DNA sequences to stop coat production at those sites, thereby maintaining a uniform coat. If correct, competition for the regulatory protein would result in a ‘winner-takes-all’ scenario, whereby one coat-producing gene emerges victorious (making all of the coat). Several experimental observations support our model but the details remain to be elucidated. My aim is to manipulate trypanosomes in such a way that coat production is either on or off. These trypanosomes will then be characterised using cell and molecular biology techniques.