Defining the cytoplasmic architecture that control bacterial type three secretion

许多致病细菌使用纳米机器将蛋白质注入宿主细胞，以促进细菌的感染和定植。其中一台这样的机器被称为三型分泌系统或T3SS。这项申请旨在通过结合使用不同的结构和功能方法来研究细菌选择和分泌蛋白质的方式。特别是，我们将研究在细菌内组装的两个机器部件，遗传证据表明，这两个部件对于选择哪些蛋白质应该注入宿主的过程很重要，也与驱动注射的实际过程有关。通过使用方法，我们可以“看到”机器的这些部分是如何构造的，并辅之以研究，我们对构成机器的部件进行微小的改变，并查看这对机器的功能有什么影响，我们希望推断出控制的分子机制。由于这种机制只在细菌中发现，因此对T3SS的良好理解最终可能导致新的抗生素，这些抗生素被设计成专门干扰这一关键活动。

Many pathogenic bacteria use nano-machines to inject proteins into their hosts' cells to promote infection and colonisation by the bacterium. One such machine is called the Type Three Secretion System or T3SS. This application seeks to investigate the way in which bacteria select and secrete proteins by using a combination of different structural and functional methods. In particular we will study two pieces of the machine that are assembled within the bacterium which genetic evidence suggests are important for the process of selecting which proteins should be injected into the host and are also implicated in the actual process of driving injection. By using methods which allow us to "see" how these parts of the machine are constructed and complementing this with studies where we make small changes in the components from which the machines are constructed and look to see what effect this has on the function of the machinery we hope to deduce the molecular mechanisms of control. Since this machinery is only found in bacteria there is the potential that a good understanding of the T3SS will eventually lead to new antibiotics which are designed to specifically interfere with this key activity.