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

描述（由申请人提供）：本研究的总体目标是了解群体感应：细菌中细胞间通讯的过程。该应用将重点关注两种相关细菌的群体感应：霍乱弧菌（一种主要的人类病原体）和海洋细菌哈维氏弧菌。这些细菌中的群体感应系统将多个群体感应信号引导到一个信号电路中。该电路的核心是多个小调节 RNA (sRNA)，它们介导群体感应开关并允许细胞共同调节基因表达。该应用的具体目标是（1）开发霍乱弧菌和哈维弧菌群体感应电路的定量模型，以及（2）开发一个新的理论框架，用于分析弧菌群体感应电路如何使用工程和物理学的分析工具来整合感觉信息。开发用于分析信息流的定量模型和理论框架将有助于回答三个基本问题。 （1）即使多个信号通过共享途径传输，弧菌群体感应网络如何保持信号转导特异性？ (2) 群体感应回路中 RNA 调节因子（相对于 DNA 结合蛋白）提供的信号传导的相对优势是什么？ (3) 群体感应电路中的主要噪声源是什么？这些噪声对信号特性有何影响？回答这些问题将有助于我们了解细菌的种内和种间通讯以及细胞回路中信息处理和信号转导的原理。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。这项研究还具有重要的健康意义，因为霍乱（霍乱弧菌）等许多病原体使用群体感应来调节毒力。因此，对群体感应的更深入了解可能会带来控制感染的新药物。

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.