Intra- and Inter Species Communication in Bacteria

描述（由申请人提供）：我的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。拟议的研究将探讨群体感应如何在相对自然的环境中发挥作用，这些环境包含多种细菌，在空间和时间上是异质的，并经历条件的波动。在最一般的层面上，拟议的工作将提供深入了解内部和内部 物种交流，种群水平的合作，以及信号转导和信息处理的网络原理。在更具体的层面上，该研究将促进对群体感应的特定化学输入和遗传输出，小RNA介导的基因表达控制的机制以及生物膜形成的进化和物理化学驱动因素的理解。在实践层面上，我的团队的研究可能会导致控制群体感应的策略，包括针对利用群体感应控制毒性和生物膜形成的细菌的抗菌药物的开发，以及改善天然产品的工业生产。拟议的研究依赖于霍乱弧菌和哈维氏弧菌的体内遗传操作和表型分析。该研究采用了纯化蛋白质，DNA和小分子配体，全基因组微阵列，ChIP测序和荧光成像的体外生化测定。我们还将使用荧光显微镜结合微流体技术来量化液体培养物和不同几何形状的生物膜室中以及不同流动和扰动条件下的单个细菌细胞中的群体感应。 公共卫生相关性：群体感应是一种细胞间通讯的过程，允许细菌共同控制包括生物膜形成和毒力因子分泌在内的过程。我们的研究将探讨群体感应功能在相对自然的环境中如何发挥作用，这些环境包含多种细菌，在空间和时间上是异质的，并经历条件的波动。我的团队的研究可能会导致控制群体感应的策略，包括针对利用群体感应控制毒性和生物膜形成的细菌的抗微生物药物的开发，以及改善天然产品的工业生产。

DESCRIPTION (provided by applicant): The overall goal of my research is to understand quorum sensing: the process of cell-cell communication in bacteria. The proposed research will probe how quorum sensing functions in relatively natural environments that contain multiple species of bacteria, are spatially and temporally heterogeneous, and undergo fluctuations in conditions. At the most general level, the proposed work will provide insight into intra- and inter species communication, population-level cooperation, and the network principles underlying signal transduction and information processing. At a more specific level, the research will advance the understanding of the specific chemical inputs and genetic outputs of quorum sensing, the mechanisms underlying small-RNA-mediated control of gene expression, and the evolutionary and physico-chemical drivers of biofilm formation. At a practical level, my group's investigations could lead to strategies for controlling quorum sensing, including development of anti-microbial drugs aimed at bacteria that use quorum sensing to control virulence and biofilm formation, and improved industrial production of natural products. The proposed research relies on in vivo genetic manipulation and phenotypic analyses of Vibrio cholerae and Vibrio harveyi. The research employs in vitro biochemical assays with purified proteins, DNA, and small molecule ligands, whole-genome microarrays, ChIP-sequencing, and fluorescent imaging. We will also use fluorescence microscopy combined with microfluidics to quantify quorum sensing in individual bacterial cells in liquid cultures and in biofilm chambers of different geometries and under different flow and perturbation conditions. PUBLIC HEALTH RELEVANCE: Quorum sensing is a process of cell-cell communication that allows bacteria to collectively control processes including biofilm formation and the secretion of virulence factors. Our research will probe how quorum sensing functions in relatively natural environments that contain multiple species of bacteria, are spatially and temporally heterogeneous, and undergo fluctuations in conditions. My group's investigations could lead to strategies for controlling quorum sensing, including development of anti-microbial drugs aimed at bacteria that use quorum sensing to control virulence and biofilm formation, and improved industrial production of natural products.