**SSA** Exploring the function of T3SS effectors during in vivo infection.

伦敦帝国理工学院目前的项目主要旨在通过使用完善的啮齿类C.小鼠肠道感染模型来阐明单个A/E病原体T3 SS效应子的功能。为了实现这个目标，我将：补充一个C。用允许缺失的效应子过表达的质粒对效应子敲除的啮齿动物文库进行鉴定，从而允许对效应子的不存在以及过量的效应子的存在进行功能研究。啮齿类动物基因敲除突变体和互补菌株的体外研究。在体外初步结果之后，最有希望的菌株将在体内进行测试，其中感染谱将被表征并与C.啮齿动物野生型感染。这将阐明效应子的缺失和过表达将如何影响IEC的发病机制并影响体内T3 SS管道。此外，它将突出每个效应器的目标过程，并分析它们可能相互作用的反馈信号。最后，有趣的结果将通过更深入的分析来跟进，例如效应子中的点突变以改变活性或与其他蛋白质的结合

This current project at Imperial College London broadly aims to unravel the function of the individual A/E pathogen T3SS effectors by using the well-established C.rodentium mouse model of gut infection. In order to accomplish this objective, I will: Complement a C. rodentium library of the effector knockouts with a plasmid that allows the overexpression of the deleted effector, allowing the functional study of both the absence of the effector as well as the presence of excess quantities of it. Characterise the library of C. rodentium knock-out mutants and the complemented strains in vitro. After the preliminary results in vitro, the most promising strains will be tested in vivo, where the infection profile will be characterised and compared to C. rodentium wild-type infections. This will clarify how the deletion and overexpression of effectors would affect the pathogenesis in IECs and impact on the T3SS conduit in vivo. Additionally, it will highlight processes targeted by each effector and analyse feedback signals they may have upon each other. Finally, interesting results will be followed-up by more in depth analysis e.g point mutations in the effectors to modify activity or binding to other proteins