Professor David Horn
Biological Chemistry and Drug Discovery, School of Life Sciences
African trypanosomes are parasitic protists which cause sleeping sickness or Human African Trypanosomiasis (HAT) and the livestock disease, nagana. They are masters of antigenic variation and immune evasion in the host bloodstream. One goal is to understand the molecular mechanisms underlying this process. DNA repair is required to replace the active Variant Surface Glycoprotein (VSG) gene with a new VSG and VSG expression is monoallelic (at a telomere) so our work in this area focuses on understanding mechanisms of DNA recombination and monotelomeric gene expression.
We also seek to understand drug action and resistance. We recently identified >50 genes linked to drug action. Suramin uptake was shown to be via receptor (ISG75)-mediated endocytosis while an aquaglyceroporin (AQP2) controls melarsoprol-pentamidine cross-resistance; AQP2 has now also been linked to clinical cases of melarsoprol resistance.
Our exploitation of genome sequence data is underpinned by technology development. In particular, we have developed an RNAi library screening method called RNA Interference Target sequencing or RIT-seq. Our research is supported by the Wellcome Trust and the Medical Research Council and DH is a Wellcome Trust Senior Investigator.
A team from the Wellcome Centre for Anti-Infectives Research (WCAIR) at the University of Dundee has used a high-throughput genetic screen to decode mechanisms underpinning the trypanosome cell cycle.
A team from the Wellcome Centre for Anti-Infectives Research (WCAIR) at the University of Dundee has developed a new parasite gene-editing technology.
The life-changing work of one of Scotland’s foremost scientific institutions is to continue following a multi-million-pound award.
Antigenic variation, drug resistance and RNAi screens in trypanosomes
|Major Personal Funding Awards / Wellcome Investigator Award||2019|
|International Science Prizes awarded since 1990 / William Trager Award for Basic Parasitology||2019|
|Fellows of the Royal Society of Edinburgh||2017|
|National Sciences Prizes awarded since 1990 / C.A. Wright Memorial Medal||2016|
|Major Personal Funding Awards / Wellcome Trust Senior Investigator Award||2012|