Investigating the molecular determinants of inter-bacterial competition

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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. Many, diverse bacteria, including important 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. Importantly, understanding the lethal consequences of T6SS anti-bacterial effectors on targeted bacterial cells offers the potential to uncover new ways to kill or inhibit bacterial pathogens. In this project we aim to determine the molecular basis of the toxicity of one or more novel anti-bacterial effectors, using a combination of genetic, biochemical, biophysical and structural approaches.1.Explain interdisciplinary interface: This project will develop my interdisciplinary knowledge and skills at the interface of bioscience-physics, as well as fundamental biochemistry. This will be conducted through purification of novel toxins, which shall enable us to evaluate their toxic activity using various biochemical assays. These toxins will also be used in attempts to crystallize and subsequently solve their structures.2.Does project require significant amount of quantitative skills? NO 3.Does project require significant amount of whole organism physiology skills? NO