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

细菌存在于多菌群落中，VI型分泌系统(T6SS)被许多革兰氏阴性细菌用来将有毒的“效应器”蛋白输送到邻近的细菌细胞中，作为细菌间竞争的一种方法。了解T6SS在多菌群落中的机制和作用，包括那些对健康和疾病重要的微生物群落，有可能提高我们开发疾病治疗的能力。使用多学科方法，我们的目标是：1.开发先进的显微镜技术，以可视化单个效应器及其相互作用的核心T6SS组件。从粘质链球菌的临床分离株中鉴定并表征一种新的T6SS效应器的作用模式。我们的发现将定义一种新的效应器蛋白的活性，开发新的技术来理解效应器的作用模式，并解决有关效应器分子如何传递的重要生物学问题。

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.