China Scholarship Council 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, also known as Human African Trypanosomiasis, which is typically fatal if left untreated, and the livestock disease known as nagana. Molecular mechanisms underlying antigenic variation, gene expression control, drug action and other fundamental processes remain to be characterized. We have developed (loss-of-function1-3, gain-of-function4 and reporter-based) genetic screens that facilitate unbiased genome-scale functional analyses; as well as CRISPR-Cas9 gene editing4-5. These are being used to decode the genetic basis key aspects of T. brucei biology, including:

Antigenic variation and gene-expression control 3
Drug mode of action and resistance 1,4
A range of genetic, molecular, cell biology and biochemical techniques are being applied to these problems, focusing on the genes and proteins that play the major roles in each process. We also work with the Dundee Drug Discovery Unit with the goal of helping to develop improved antitrypanosomal therapies. The Ph.D. project will focus on a specific area, as outlined above and will contribute to these goals.