A quantitative study of cell-to-cell communication in bacteria

细菌细胞间通讯的定量研究

• 批准号: 7905836
• 负责人: Pankaj Mehta
• 金额: $ 12.94万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7905836
• 关键词: Accounting; Bacteria; Biochemical; Biological; Cell Communication; Cell physiology; Cells; Cholera; Communication; Communication Aids for Disabled; Complex; Controlled Study; Cues; DNA-Binding Proteins; Data; Development; Elements; Engineering; Environment; Fluorescence Microscopy; Gene Expression; Goals; Health; Heart; Human; Infection Control; Information Theory; Kinetics; Lead; Learning; Marines; Mediating; Modeling; Neurosciences; Noise; Output; Pathway interactions; Pharmaceutical Preparations; Phosphotransferases; Physics; Process; Property; RNA; Research; Research Personnel; Role; Sensory; Signal Transduction; Signaling Molecule; Small RNA; Source; Specificity; Stimulus; System; Techniques; Theoretical model; Vibrio; Vibrio cholerae; Virulence; analytical tool; comparative; computerized data processing; information processing; mathematical theory; novel; pathogen; programs; promoter; quorum sensing; research study; response; simulation; tool

DESCRIPTION (provided by applicant): The overall goal of this research is to understand quorum sensing: the process of cell-to-cell communication in bacteria. This application will focus on quorum sensing in two related bacteria: Vibrio cholerae, a major human pathogen and the marine-bacteria Vibrio harveyi. The quorum- sensing systems in these bacteria channel multiple quorum-sensing signals into one signaling circuit. At the heart of this circuit are multiple small regulatory RNAs (sRNAs) that mediate the quorum-sensing switch and allow cells to collectively regulate gene expression. The specific goals of this application are (1) to develop a quantitative model for the quorum sensing circuit in V. cholerae and V. harveyi and (2) to develop a new theoretical framework for analyzing how sensory information is integrated by the Vibrio quorum sensing circuit using analytical tools from engineering and physics. Developing a quantitative model and theoretical framework for analyzing information flow will help answer three fundamental questions. (1) How can the Vibrio quorum-sensing network maintain signal-transduction specificity even when multiple signals are transmitted through a shared pathway? (2) What are the comparative advantages for signaling provided by RNA regulators (as opposed to DNA-binding proteins) in the quorum- sensing circuit? (3) What are the major sources of noise in the quorum-sensing circuit and what is the effect of this noise on signaling properties? Answering these questions will contribute to our understanding of intra- and inter-species communication in bacteria and the principles underlying information processing and signaling-transduction in cellular circuits. From a broad modeling perspective, this research is likely to yield new analytic and quantitative tools for analyzing signal-transduction and information flow in biochemical networks. This research also has important health implications because many pathogens such as cholera (Vibrio cholerae) use quorum sensing to regulate virulence. Thus, a greater understanding of quorum-sensing may lead to novel drugs to control infection.

描述（由申请人提供）：这项研究的总体目标是了解法规传感：细菌中细胞对细胞通信的过程。该应用将集中于两种相关细菌中的法定人数：弧菌霍乱，一种主要的人类病原体和海洋 - 细菌弧菌Harveyi。这些细菌中的法定感应系统将多个法定信号信号通向一个信号电路。该电路的核心是多个小的调节RNA（SRNA），可介导群体感应开关并允许细胞集体调节基因表达。该应用程序的具体目标是（1）为V. cholerae和V. harveyi中的群体传感电路的定量模型和（2）开发一个新的理论框架，用于分析使用工程和物理学的分析工具分析的弧形法定人数传感电路如何通过工程和物理学的分析电路整合感官信息。开发一个定量模型和理论框架来分析信息流将有助于回答三个基本问题。 （1）即使在通过共享途径传输多个信号时，纤维群群体感应网络即使如何保持信号转导特异性？ （2）在法定感应电路中，RNA调节剂（与DNA结合蛋白相反）提供的信号传导的比较优势是什么？ （3）法定感应电路中噪声的主要来源是什么？这种噪声对信号传导特性有什么影响？回答这些问题将有助于我们对细菌中种内和种间交流以及细胞中的原理处理以及细胞电路中的信号传导转移。从广泛的建模角度来看，这项研究可能会产生新的分析和定量工具，用于分析生化网络中的信号转导和信息流。这项研究也具有重要的健康影响，因为许多病原体（例如霍乱（圆锥形霍乱））使用法定人数调节毒力。因此，对法定感应的更深入的了解可能导致新的药物控制感染。