School of Infection & Immunity

Dr Kirsty McWilliam

  • Postdoctoral Research Associate at School of Biological Sciences, University of Edinburgh
  • Location: Room C222, BHF & Zoom
  • Passcode: 407357

Title: Genome-wide fitness profiling identifies novel regulators of Trypanosoma brucei life cycle development

Synopsis:

In its mammalian host, Trypanosoma brucei undergoes a density-dependent developmental transition reminiscent of bacterial quorum sensing (QS). Proliferative ‘slender’ cells differentiate into cell-cycle arrested and transmission-competent ‘stumpy’ cells in response to increasing concentrations of extracellular oligopeptides imported via the surface transporter TbGPR89. Although a previous genome-wide RNAi screen identified molecules that form a QS signal transduction pathway, the molecules that initiate pathway activation remain unknown.

To identify these, we used Direct RNAi Fragment Sequencing (DRiF-Seq) to perform genome-wide quantitative fitness profiling of developmentally competent (pleomorphic) parasites exposed to the physiological oligopeptide differentiation signal. We identify and characterise a novel regulator of differentiation, the kinase ‘TbAKT-like’. We demonstrate its importance for differentiation in vitro and in vivo and define residues required for its regulation and activity. Biochemical and quantitative phosphoproteomic analyses identify potential TbAKT-like substrates in the QS signalling pathway that are differentially phosphorylated during in vivo differentiation and place TbAKT-like upstream of all previously identified QS pathway components. Our results present an exciting insight into the earliest signalling events controlling bloodstream T. brucei development.

Bio:

After a stint as a pro triathlete, Kirsty (who grew up ‘just down the road’ near the Campsie Hills) began her University studies in Glasgow studying Parasitology. Kirsty took part in the MSci work placement programme and moved to Mainz, Germany, where she worked for a year with MSD Animal Health as part of the Assay Development Team. After graduating, Kirsty moved to Edinburgh and began her PhD in 2015 in Keith Matthews’ Lab where she studied the interplay between antigenic variation and differentiation in T. brucei. Following her PhD, Kirsty moved back to Germany with an LMU Postdoctoral Fellowship to work in Nicolai Siegel’s Lab in Munich. Here she worked to establish a trypanosome-specific single cell RNA sequencing method and used this to study the genetic determinants of the T. brucei antigen expression hierarchy. In 2022, Kirsty moved back to her beloved Scotland and now works as a postdoc in the Matthews Lab studying signalling during T. brucei development.

First published: 30 January 2026

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