Molecular mechanisms controlling stress responses and cell adhesion in bacteria

项目摘要/摘要 我的团队试图了解细菌细胞能力的分子机制 在复杂、动态的环境中生存，包括哺乳动物宿主。在此背景下 项目中，我们将专门专注于定义细菌(I)调节其 生理，以生存环境压力，和(Ii)调节和修改其包膜，以控制 与表面和其他细胞的粘附性。我们将利用一套跨学科的基因， 解决这些问题的生化、生物物理和计算方法 规模，从细胞/系统水平到分子结构水平。浮现的数据 我们的研究将加强对细菌生长和生长过程的理解 在复杂的环境中生存，并将提供基因调控和细胞方面的新概念 包络生物学。更具体地说，这个项目将为科学界提供一个 从信号检测到细胞，对感觉转导机制的综合理解 回应。此外，我们对细菌细胞黏附和包膜多糖的研究 生物合成将提高对分子机制的理解，通过这些机制， 细菌构建了高度复杂的结构，称为包膜，它紧密地将 从外部世界控制细胞质中的活动。重要的是，环境方面的 细菌细胞膜的调节蛋白和成分是明确定义的毒力 许多细菌病原体中的决定因素。因此，我们的工作有可能为新的 控制某些细菌感染的治疗途径。

Project Summary/Abstract My group seeks to understand molecular mechanisms that underlie the ability of bacterial cells to survive in complex, dynamic environments, including mammalian hosts. In the context of this project, we will specifically focus on defining mechanisms by which bacteria (i) regulate their physiology to survive environmental stress, and (ii) regulate and modify their envelope to control adhesion to surfaces and to other cells. We will utilize an interdisciplinary set of genetic, biochemical, biophysical, and computational approaches to address these questions on multiple scales, from the cellular/systems level to the level of molecular structure. The data that emerge from our studies will enhance understanding of processes that allow bacteria to grow and survive in complex environments, and will inform new concepts in gene regulation and cell envelope biology. More specifically, this project will provide the scientific community with an integrative understanding of sensory transduction mechanisms, from signal detection to cellular response. In addition, our investigations of bacterial cell adhesion and envelope polysaccharide biosynthesis will lead to improved understanding of the molecular mechanisms by which bacteria build the highly complex structure known as the envelope, which separates the tightly controlled activities in the cytoplasm from the outside world. Importantly, both environmental regulatory proteins and components of the bacterial cell envelope are well-defined virulence determinants in many bacterial pathogens. Thus our work has the potential to inform new therapeutic routes to control certain bacterial infections.