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在体内存活的分子机制 复杂、动态的环境，包括哺乳动物宿主。在这个项目的背景下，我们将具体 重点是确定细菌(I)调节其生理以在环境压力下生存的机制， 以及(Ii)调节和修改它们的包膜以控制与表面和其他细胞的黏附。我们将利用一个 一套跨学科的遗传、生化、生物物理和计算方法来解决这些问题 从细胞/系统层面到分子结构层面的多个尺度上的问题。这些数据是 从我们的研究中发现的将加强对允许细菌在 复杂的环境，并将为基因调控和细胞被膜生物学提供新的概念。更多 具体地说，这个项目将为科学界提供对感官的综合理解 信号传导机制，从信号检测到细胞反应。此外，我们对细菌的研究 细胞黏附和包膜多糖的生物合成将促进对分子的理解 细菌构建被称为包膜的高度复杂结构的机制，它将 来自外界的严格控制细胞质中的活动。重要的是，环境监管 细菌细胞膜的蛋白质和成分在许多情况下都是明确定义的毒力决定因素 细菌病原体。因此，我们的工作有可能提供新的治疗途径，以控制某些 细菌感染。

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.