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 (loss-of-function1-3, gain-of-function4, 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 of aspects of T. brucei biology, in particular:
• Antigenic variation and gene-expression control3
• Drug mode of action and resistance1,4
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 anti-trypanosomal therapies. A Ph.D. project in the Horn lab would focus on a specific area, and contribute to these goals, as outlined above.