Development and application of advanced fluorescence microscopy approaches to study Type VI secretion system effector delivery in vivo.

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Bacteria exist in polymicrobial communities and the Type VI Secretion System (T6SS) is used by many Gram-negative bacteria to deliver toxic 'effector' proteins into neighbouring bacterial cells as a method of inter-bacterial competition. Understanding the T6SS's mechanism and role in polymicrobial communities, including those important for health and disease, has the potential to increase our ability to develop disease therapies. Using multidisciplinary approaches, we aim to:1. Develop advanced microscopy techniques to visualise individual effectors and the core T6SS components they interact with.2. Identify and characterise the mode of action of a new T6SS effector from a clinical isolate of S. marcescens.3. Build on aims 1 and 2 to gain further mechanistic insight into effector delivery.Our findings will define the activity of a new effector protein, develop new techniques to understand effector mode of action, and address important biological questions about how effector molecules are delivered.