Genetic and microbiological tools to unravel the mechanism of action of novel anti-tuberculosis new chemical entities

Despite the existence of treatments for tuberculosis (TB), it continues to present a major healthcare challenge, accounting for nearly nine million new infections and over one million deaths per annum. Treating TB requires a drug cocktail given for at least six months, and extending to two years for infections with multi drug-resistant strains of Mycobacterium tuberculosis. A largely successful campaign by the WHO to stem the rise of TB has not diminished the urgent need for better drugs and new cellular targets to alleviate the devastating impact of this disease. This MRC IMPACT PhD studentship has the principal aim of taking selected hits from a whole-cell phenotypic screen, which will then be the focus of genetic, chemical proteomic and structural studies with the aim of identifying and validating their cellular targets, and establishing their modes of action. The guiding principle of this multi-disciplinary PhD studentship will be to focus on a small set of potent compounds hitting diverse targets; with the goal of identifying new and better anti-TB drugs with novel modes of action, and to gain new insights into the fundamental biology of M. tuberculosis.