Integrated Control of Caulobacter Cell Physiology by Visible Light and Stress

这项提案的长期目标是定义细菌如何调节它们的生理、生长和 根据环境中的化学和物理变化而发展的生物。这里描述的项目 利用一套跨学科和创新的遗传、生化、生物物理和计算 将在多个范围内解决这个问题的方法，从蜂窝/系统级别到 分子结构。拟议的实验具有生物学意义，不仅对细菌的研究 信号转导，但细胞信号一般。本项目取得的成果将为今后的研究提供科学依据。 对从信号检测到细胞的细菌感觉转导有全面了解的社区 回应。重要的是，由于一些环境调节蛋白已被定义为毒力 细菌病原体的决定因素，这项工作有可能提供新的治疗途径来控制 某些细菌感染。 研究将特别集中在多蛋白调控系统上，该系统可以感知和 整合有关光环境、化学和物理应激源以及细胞氧化还原状态的信息。 这一调控系统将在模式细菌新月弯杆菌中进行研究。然而， 编码这个系统的基因在许多与人类健康有关的细菌物种中保守，包括 病原体是流产布鲁氏菌。 该项目的具体目标是： 1)确定LovK-LovR通过两个不同的 调控途径 2)研究HfiA作为细胞表面粘附素抑制因子的分子基础。 3)确定PHYR通过磷酸化激活的结构基础。

The long-term goal of this proposal is to define how bacteria modulate their physiology, growth, and development in response to chemical and physical changes in their environment. The project described here utilizes an interdisciplinary and innovative set of genetic, biochemical, biophysical, and computational approaches that will address this question on multiple scales, from the cellular/systems level to the level of molecular structure. The proposed experiments are of biological import, not only to the study of bacterial signal transduction, but cell signaling in general. Results obtained from this project will provide the scientific community with an integrative understanding of bacterial sensory transduction, from signal detection to cellular response. Importantly, as a number of environmental regulatory proteins have been defined as virulence determinants in bacterial pathogens, this work has the potential to inform new therapeutic routes to control certain bacterial infections. Studies will be specifically focused on a multi-protein regulatory system that can function to sense and integrate information about the light environment, chemical and physical stressors, and cellular redox state. This regulatory system will be investigated in the model bacterium, Caulobacter crescentus. However, the genes encoding this system are conserved in a number of bacterial species relevant to human health including the pathogen, Brucella abortus. The specific aims of this project are: 1) Define the mechanism by which LovK-LovR independently controls transcription through two distinct regulatory pathways 2) Characterize the molecular basis of HfiA function as a cell surface adhesin inhibitor. 3) Define the structural basis of PhyR activation by phosphorylation.