My research programme focuses on the interactions between Trypanosoma brucei and its host environment (more details can be found at http://blogs.lshtm.ac.uk/alsfordlab/research/).

I'm particularly interested in the uptake and intracellular transit of parasite- and host-derived molecules, such as nutrients, drugs and innate immune factors, and the genetic control of antigenic variation and ribosomal RNA transcription. My research is underpinned by a combination of high-throughput forward genetic screens and reverse genetic approaches, enabling the identification and characterisation of proteins involved in the uptake and intracellular transit of these molecules, as well as the parasite's response to them.

Using a high throughput genetic screen (Currier et al, 2018), we identified 63 parasite proteins that contribute to the trypanolytic action of apolipoprotein-L1 (the toxic component of human serum trypanolytic complexes), and we're now exploring their roles in apoL1 action, as well as broader T. brucei biology. Intriguingly, ten of our putative apoL1 sensitivity determinants have roles in dynamic ubiquitination and intracellular membrane trafficking.

We've also taken a similar approach to explore anti-leishmanial drug action (Collett et al, 2019), identifying a panel of candidate drug efficacy determinants in T. brucei, which is still a more tractable system than its fellow kinetoplastid parasite, Leishmania. We're now exploring their contribution to drug efficacy and their roles in T. brucei and Leishmania biology.

We've also applied this high throughput RNAi library approach to identifying the genetic determinants of RNA polymerase-I driven VSG monoallelic expression (Glover et al 2016; Davies et al 2021). By combining the RNAi library selection with a panel of bespoke rDNA locus reporter cell lines, we're now exploring the regulation of rRNA transcription and its intersection with VSG expression and differentiation.

The full range of plasmids for tagged protein expression and RNAi knockdown in T. brucei, developed in conjunction with David Horn, are freely available to the research community - details can be found at http://blogs.lshtm.ac.uk/alsfordlab/cell-lines-plasmids/.