Modes of action for novel anti-leishmanial drugs
Supervisor: Professor Mike Barrett, School of Infection and Immunity
The requirement for new antimicrobial agents is of increasing urgency. Screening for new compounds that kill microbes is bringing new chemicals forward. However, beyond simply killing the microbial organisms it is also necessary to understand how compounds selected in this manner exert their activity. Working with the parasitic protozoan Leishmania, which afflicts millions of people in the tropics and sub-tropics, we have identified numerous compounds that are toxic to the parasite. In this rotation project, novel agents that have been shown to kill leishmania parasite will be applied to parasites and changes to cellular metabolism that result from this exposure will be ascertained using untargeted metabolomics technology. If compounds target specific enzymes, these will be identified based on the changes to metabolism associated with exposure to the drugs. Targets will then be verified using genetic modification of parasites with CRISPR-cas9 technology to confirm that putative targets are essential and that their over-expression can diminish sensitivity to the drugs.