Integrated Control of Caulobacter Cell Physiology by Visible Light and Stress

该提案的长期目标是确定细菌如何调节其生理，生长和代谢。 环境中的化学和物理变化。这里描述的项目 利用遗传学、生物化学、生物物理学和计算机科学的跨学科和创新的方法， 这些方法将在多个尺度上解决这个问题，从蜂窝/系统级别到 分子结构所提出的实验具有生物学意义，不仅仅是对细菌的研究， 信号转导，但一般的细胞信号转导。从该项目获得的结果将提供科学 社区与细菌感觉转导的综合理解，从信号检测到细胞 反应重要的是，由于一些环境调节蛋白已被定义为毒力 决定因素的细菌病原体，这项工作有可能告知新的治疗途径，以控制 某些细菌感染。 研究将特别集中在一个多蛋白质调控系统，可以发挥作用，以感测和 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。 该调节系统将在模式细菌新月柄杆菌中进行研究。但 编码该系统的基因在许多与人类健康相关的细菌物种中是保守的， 病原体流产布鲁氏菌 该项目的具体目标是： 1)定义LovK-LovR通过两个不同的机制独立控制转录 调节途径 2)表征HfiA作为细胞表面粘附素抑制剂功能的分子基础。 3)定义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.