4 Year Wellcome Trust PhD Programme: Decoding virulence mechanisms in trypanosomes

The African trypanosome, Trypanosoma brucei, is transmitted among mammalian hosts by tsetse flies. These unicellular parasites cause sleeping sickness or Human African Trypanosomiasis, typically fatal if left untreated, and the livestock disease known as nagana. Molecular mechanisms underlying antigenic variation, drug action and other fundamental processes remain to be characterised. We have developed genetic screens (using RNA interference initially) that allow unbiased genome-scale functional analysis; see Alsford et al., 2012 Nature 482:232-6; Mony et al., 2014 Nature 505:681-685; Glover et al., 2015 Nature Protocols 10:106-133, for examples. New genetic screening approaches are under development and the current approaches are being used to decode the genetic basis of aspects of T. brucei biology, including:

Antigenic variation and gene-expression control
Drug mode of action and resistance
Cell cycle control
A range of molecular, genetic and cell biology techniques are being applied to these problems, focusing on the genes and proteins that play major roles in each process, with a view to the development of improved therapies in collaboration with the Dundee Drug Discovery Unit.