4 Year Wellcome Trust PhD Programme: Understanding the role and mode of action of a bacterial nanoweapon

Many bacterial pathogens use the Type VI secretion system (T6SS) nanomachine to fire toxic ‘effector’ proteins directly into target cells. It is becoming increasingly apparent that the T6SS plays a key role in the virulence and competitiveness of diverse Gram-negative bacteria, including important human pathogens. Pathogens can use T6SSs to directly target eukaryotic organisms, as classical virulence factors. Alternatively, many pathogens can use T6SSs to target other bacterial cells, killing or inhibiting rivals. ‘Anti-bacterial’ T6SSs thus provide a competitive mechanism to allow pathogens to proliferate in polymicrobial infection sites or environmental reservoirs and ultimately cause disease. Understanding how the T6SS is deployed and the lethal consequences of its effectors on targeted cells therefore offers the potential to uncover new ways to kill or inhibit bacterial pathogens.

In the Coulthurst group, we study the role, mode of action and effectors of the T6SS. We utilise a wide range of molecular and cellular approaches, including genetics, molecular biology, microscopy, biochemistry, genomics and proteomics, and focus on representative examples of Gram-negative bacterial pathogens. This project will investigate topical aspect(s) of T6SS function, effector action, or the integration of T6SS with broader competitive strategies, partly dependent on the interests of the student. The student will receive a broad training in molecular microbiology with the opportunity to additionally gain expertise in biochemistry, cell biology and/or ‘omics approaches.