Professor David Horn - University of Dundee

Event details

Abstract

Trypanosomatid parasites must adapt to changing host environments, and they use post-transcriptional mRNA-based controls to do so. We have developed and are exploiting high-throughput genomics approaches to understand how ‘first responder’ RNA-binding proteins (RBPs) connect environmental cues to adaptive responses​ via a cis-regulatory code within untranslated regions (UTRs); one goal is to be able to predict expression from UTR sequences alone. I will introduce massive parallel reporter assays for screening UTRs, and will present examples relating to zinc-sensing and uptake control by a zinc-finger nuclease, as well as thermo-sensing and heat-stress responses. An RBP that controls polycistronic mRNA processing is also the target of the ‘game-changing’ anti-trypanosomal drug, acoziborole. This drug is in fact a dual-action inhibitor and degrader, and we are using gene-editing to further probe the acoziborole – RBP target interaction.