How is regulation of motility and chemotaxis required for pathogenicity in Helicobacter pylori, specifically for toxin delivery of VacA.

幽门螺杆菌引起胃炎和胃癌。结果表明，运动调节在致病性中起重要作用。因此，有人认为细菌附着在上皮细胞上依赖于受调节的运动性和趋化性来传递毒素。对一种重要的毒素VacA进行了详细的研究，并表明VacA是如何导致上皮细胞死亡的。在我的研究项目中，我想研究幽门螺杆菌细胞如何在上皮细胞或上皮细胞附近找到它们的位置来转移毒素VacA，以及为什么趋化性对这一过程至关重要。为了找出VacA转移与趋化性之间的关系，我将首先分析趋化性引起的致病性是否直接依赖于VacA。为此，我研究了VacA和趋化蛋白是否在一个信号通路内，以及我是否可以通过增加VacA表达来恢复幽门螺杆菌趋化突变体降低的致病性。此外，我想知道幽门螺杆菌细胞是否必须附着在上皮细胞上才能转移毒素VacA，附着是否会导致毒素产生增加。除了在老鼠身上进行的实验，我想建立一个新的系统，胃类器官。使用胃类器官，我将拥有一个高度可复制的系统，并将能够最大限度地减少动物试验。为了对趋化性对致病性的作用有新的认识，我想在共聚焦显微镜下记录被感染的类器官的视频，看看没有趋化性的突变体与野生型相比，什么时候表现不同。

Helicobacter pylori causes gastritis and gastric cancer. It was shown that the regulation of motility plays an important role for the pathogenicity. Therefore, it has been suggested that the bacteria attach to the epithelial cells depending on regulated motility and chemotaxis to deliver toxins. An important toxin, VacA, has been studied in detail and it was shown how VacA causes cell death of epithelial cells. In my research project I want to investigate how H. pylori cells find their position at or in the vicinity of epithelial cells to transfer the toxin VacA and why chemotaxis is crucial for that process. To find the relationship between VacA transfer and chemotaxis, I will first analyze whether the pathogenicity, which is caused by chemotaxis, directly dependents on VacA. For this, I examine whether VacA and chemotaxis proteins are within one signalling pathway, and if I can restore the reduced pathogenicity of H. pylori chemotaxis mutants by increased VacA expression. Furthermore, I want to find out whether H. pylori cells must be attached to epithelial cells to transfer the toxin VacA and whether attachment leads to increased toxin production. In addition to the experiments carried out with mice I want to establish a new system, the gastric organoids. Using gastric organoids I would have a highly reproducable system and will be able to minimize animal testing. To get new insights into the function of chemotaxis for pathogenicity, I want to record videos of the infected organoids under a confocal microscope to see when a mutant without chemotaxis behaves different compared to the wild type.