Integrated Control of Caulobacter Cell Physiology by Visible Light and Stress

可见光和压力对柄杆菌细胞生理学的综合控制

• 批准号: 9125850
• 负责人: Sean Crosson
• 金额: $ 30.56万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9125850
• 关键词: Address; Adhesions; Alpha Cell; Bacteria; Bacterial Adhesins; Bacterial Infections; Bacterial Physiology; Binding; Biochemical; Biological; Biology; Brucella abortus; Caulobacter; Caulobacter crescentus; Cell Adhesion; Cell physiology; Cell surface; Cells; Chemicals; Clinical; Communities; DNA Binding Domain; Data; Detection; Development; Environment; Family; Feedback; Flavins; Foundations; Gap Junctions; Gene Expression; Genes; Genetic; Genetic Transcription; Goals; Growth; Growth and Development function; Health; Human; Infection; Life; Life Style; Light; Logic; Modeling; Molecular; Molecular Structure; Monitor; Oxidation-Reduction; Pathway interactions; Phosphorylation; Phosphotransferases; Physiology; Planets; Polysaccharides; Positioning Attribute; Proteins; Proteobacteria; Regulation; Regulatory Pathway; Regulon; Route; Sensory; Sigma Factor; Signal Transduction; Stress; Surface; System; Testing; Transcriptional Regulation; Virulence; Visible Radiation; Work; base; biological adaptation to stress; cofactor; gene function; genetic regulatory protein; glycosyltransferase; in vivo; inhibitor/antagonist; innovation; molecular scale; novel therapeutics; pathogen; protein function; research study; response; sensor; sensory system; stressor

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.

该提案的长期目标是确定细菌如何调节其生理、生长和生长。 其发展是为了应对环境中的化学和物理变化。这里描述的项目 利用遗传、生物化学、生物物理和计算的跨学科和创新组合 将在多个尺度上解决这个问题的方法，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，不仅对细菌的研究 信号转导，但一般是细胞信号转导。该项目获得的结果将提供科学依据 对细菌感觉转导（从信号检测到细胞）有综合理解的社区 回复。重要的是，由于许多环境调节蛋白已被定义为毒力 细菌病原体的决定因素，这项工作有可能为控制细菌病原体的新治疗途径提供信息 某些细菌感染。 研究将特别关注多蛋白调节系统，该系统可以感知和 整合有关光环境、化学和物理压力源以及细胞氧化还原状态的信息。 该调节系统将在模型细菌新月柄杆菌中进行研究。然而， 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，包括 病原体，流产布鲁氏菌。 该项目的具体目标是： 1）定义LovK-LovR通过两种不同的方式独立控制转录的机制 监管途径 2) 表征 HfiA 作为细胞表面粘附素抑制剂的分子基础。 3) 定义通过磷酸化激活PhyR的结构基础。