Cellular Entry Route for Viral and Bacterial Pathogens

病毒和许多细菌必须侵入细胞才能复制，而细胞进入是一个有用的步骤， 抑制剂。病原体进入的研究促进了我们对基本细胞生物学过程和 导致了新的分子机制的发现，同时也提供了考虑新的 干预策略。在过去的十年中，使用生物化学、遗传学和实时 成像导致了对病原体摄取的许多可选模式的识别，有时 在部署特定蜂窝结构的方式上存在细微但关键的差异。直接荧光 对个体内化事件的成像，适当时与药理学或遗传学相结合 微扰，解决了与“集合”测量相关的模糊性，我们依赖于它的使用 贯穿整个提案。 本项目的重点是了解多种形式的网状蛋白介导的内吞作用对病毒的作用。 条目以及它们如何与内吞病毒的目的地相关，与战略相关的信息 抑制进入，分析细胞嗜性和不同组织感染的不同结局，并 从带有异源包膜蛋白的假型病毒进入到进入的信息 真正的病毒粒子。该项目还旨在了解网状蛋白内吞机械在 由侵袭性和粘附性细菌病原体感染。

Viruses and many bacteria must invade a cell to replicate, and cell entry is a step usefully accessible to inhibitors. Studies of pathogen entry have advanced our understanding of basic cell biological processes and led to discovery of new molecular mechanisms, while also providing opportunities to consider novel strategies for intervention. During the last decade, approaches using biochemistry, genetics, and real-time imaging have led to identification of a number of alternative modes of pathogen uptake, with sometimes subtle, yet critical differences in the way particular cellular structures are deployed. Direct fluorescence imaging of individual internalization events, combined when appropriate with pharmacological or genetic perturbation, resolves ambiguities associated with "ensemble" measurements, and we rely on its use throughout this proposal. This project focuses on understanding the role of multiple modes of clathrin-mediated endocytosis for viral entry and how they relate to the destination of endocytosed virus, information that is relevant to strategies for inhibiting entry, to analysis of cell tropism and different outcomes for infection of different tissues, and to relating information from entry of pseudotyped viruses with heterologous envelope proteins to entry of authentic virions. This project also aims to understand the role of the clathrin endocytic machinery in infection by invasive and adherent bacterial pathogens.