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

伦敦帝国理工学院目前的这一项目主要旨在通过使用公认的轮状芽胞杆菌肠道感染小鼠模型来揭示单个A/E病原体T3SS效应器的功能。为了实现这一目标，我将：用一种允许缺失效应器过表达的质粒来补充效应器敲除的轮齿芽孢杆菌文库，从而可以对效应器的缺失和存在过量的效应器进行功能研究。体外鉴定轮齿冠藻基因敲除突变体和互补菌株的文库。在体外的初步结果之后，最有希望的菌株将在体内进行测试，感染情况将被描述，并与轮状芽胞杆菌野生型感染进行比较。这将阐明效应分子的缺失和过表达如何影响IECS的发病机制，以及对体内T3SS管道的影响。此外，它还将突出每个效应器针对的过程，并分析它们可能对彼此产生的反馈信号。最后，有趣的结果将被更深入的分析跟进，例如效应器上的点突变来改变活性或与其他蛋白质结合

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