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 and gene expression control remain to be fully characterized. We have developed loss-of-function1-2 and gain-of-function3 genetic screens that facilitate unbiased genome-scale functional analyses; as well as CRISPR-Cas9 gene editing3. These approaches are being used to decode the genetic basis of key aspects of T. brucei biology and gene expression.
A range of genetic, molecular, cell biology and biochemical techniques will be 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 as part of our Wellcome Trust Centre for Anti-Infectives Research, with the goal of developing improved antitrypanosomal therapies. The Ph.D. project will focus on a specific question relating to gene expression control; Variant Surface glycoprotein allelic exclusion and antigenic variation, histone post-translational modification, post-transcription controls by RNA binding proteins or intron function (trypanosomes have only two introns, less than any other nucleated cell).
1. Alsford et al., 2012 Nature 482:232-6
2. Mony et al., 2014 Nature 505:681-5
3. Wall et al., 2018 Proc. Nat'l Acad. Sci. USA. 115:9616-21