Intercellular Signaling in Vibrio Harveyi

哈维氏弧菌的细胞间信号转导

• 批准号: 0948112
• 负责人: Thomas Silhavy
• 金额: $ 82.37万
• 依托单位: Princeton University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-15 至 2017-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0948112&HistoricalAwards=false
• 关键词: Intercellular; Signaling; Vibrio; Harveyi

Intellectual Merit: The overall goal of this project is to understand quorum sensing: the process of cell-cell communication in bacteria. Quorum sensing involves the production, release, and subsequent detection of chemical signal molecules called autoinducers. This process enables populations of bacteria to regulate gene expression, and therefore behavior, on a community-wide scale. The ability to produce and simultaneously detect multiple autoinducers was first discovered, and is best studied, in Vibrio harveyi which uses three autoinducers for intra-species, intra-genera, and inter-species cell-cell communication. Thus, the V. harveyi quorum-sensing circuit has revealed itself to be ideally suited for explorations of questions concerning how sensory information is integrated and transduced to control gene expression. The research in this project focuses on five non-coding small RNAs (sRNAs) that lie at the heart of the V. harveyi quorum-sensing circuit and are responsible for collecting the autoinducer input information and converting it into the quorum-sensing output response. The factors and mechanisms controlling the individual sRNAs will be defined, the individual and collective targets of each sRNA will be identified, and the unique control features provided by sRNA regulators (as opposed to DNA-binding proteins) will be discovered. At the most general level, this project will provide insight into intra- and inter-species communication, population-level cooperation, and the network principles underlying signal transduction and information processing at the cellular level. At a more specific level, this project will advance the understanding of the mechanisms of sRNA-mediated control of gene expression, the global nature of which has been, until recently, under-appreciated and under-studied in bacteria. Finally, at a practical level, this project could lead to synthetic strategies for controlling quorum sensing. Broader Impacts: As part of this project, undergraduate lecture and laboratory class for non-majors (MOL101: From DNA to Human Complexity) and the gateway molecular biology course for majors (MOL214: Introduction to Molecular Biology) will be taught. Furthermore, the project leader is the Chair of the Molecular Biology Department Diversity Committee responsible for recruiting graduate students from under-represented groups. She also directs the Department's science outreach efforts. She is Director of Princeton's Council on Science and Technology, responsible for developing, implementing, and vetting the University's science, math, and engineering curriculum for all non-science majors. She is President Elect of the American Society for Microbiology. She is the Howard Hughes 2009 Holiday Lecturer, and in that capacity, she is responsible for developing a series of lectures and activities for high school students on Biodiversity and the Invisible Bacterial World to be made into 100,000 DVDs and given free to US high school teachers for classroom use. The project leader works with NPR, NOVA Science Now, and TED making science pieces for lay people. With the Liz Lerman Dance Exchange, she participates in numerous activities including the traveling dance piece Ferocious Beauty Genome and a permanent exhibit at the Baltimore Science Center (Cells: The Universe Inside Us). She is on the Sloan Foundation Jury, responsible for evaluating and funding science-related screenplays. Among other duties, she has been an editor for Molecular Microbiology for a decade, she is the Chief Editor of Annual Reviews of Genetics, and she is on several other editorial boards. She serves on NAS, NIH, Keck, Damon Runyon, Burroughs Wellcome, Jane Coffin Childs, HHMI, ASM, and AAM grant, fellowship, meeting, education, and award review panels. Most importantly, the project leader is actively involved in mentoring in the laboratory. She currently has 8 graduate students, 4 postdocs, 4 undergraduates, and 3 technicians. Over the past 15 years she has mentored a total of 10 postdocs, 19 graduate students, and 31 undergraduates. This project is jointly supported by the Molecular Genetics Program and the Cellular Systems Cluster in the Division of Molecular and Cellular Biosciences.

智力优势：这个项目的总体目标是理解群体感应：细菌中细胞-细胞交流的过程。群体感应涉及到被称为自诱导剂的化学信号分子的产生、释放和随后的检测。这个过程使细菌群体能够在整个群落范围内调节基因表达，从而调节行为。产生和同时检测多种自诱导剂的能力是在哈维弧菌中首次发现的，并得到了最好的研究，该弧菌使用三种自诱导剂进行种内、属内和种间的细胞-细胞通信。因此，V. harveyi群体感应电路已经显示出它非常适合探索有关如何整合和转导感觉信息以控制基因表达的问题。本项目的研究重点是五种非编码小rna (sRNAs)，它们位于V. harveyi群体感应电路的核心，负责收集自诱导器输入信息并将其转换为群体感应输出响应。将定义控制单个sRNA的因素和机制，确定每个sRNA的单个和集体靶标，并发现sRNA调节剂（与dna结合蛋白相反）提供的独特控制特征。在最一般的层面上，该项目将提供洞察物种内和物种间的交流，种群水平的合作，以及信号转导和信息处理在细胞水平的网络原理。在更具体的层面上，该项目将促进对srna介导的基因表达控制机制的理解，直到最近，这种机制在细菌中的全球性质还没有得到充分的认识和研究。最后，在实际层面上，该项目可能导致控制群体感应的综合策略。更广泛的影响：作为该项目的一部分，将教授非专业的本科生讲座和实验课（MOL101：从DNA到人类复杂性）和专业的入门分子生物学课程（MOL214：分子生物学导论）。此外，项目负责人是分子生物系多样性委员会的主席，负责从代表性不足的群体中招募研究生。她还负责该部的科学推广工作。她是普林斯顿大学科学与技术委员会的主任，负责为所有非科学专业的学生制定、实施和审查大学的科学、数学和工程课程。她是美国微生物学会的当选主席。她是Howard Hughes 2009年的假期讲师，在这个职位上，她负责为高中生开发一系列关于生物多样性和看不见的细菌世界的讲座和活动，并制作成10万张dvd，免费提供给美国高中教师供课堂使用。项目负责人与NPR、NOVA Science Now和TED合作，为外行人制作科学作品。随着利兹·勒曼舞蹈交流，她参加了许多活动，包括巡回舞蹈作品“凶猛的美丽基因组”和巴尔的摩科学中心的永久展览（细胞：我们体内的宇宙）。她是斯隆基金会评审团成员，负责评估和资助与科学相关的电影剧本。在其他职责中，她担任《分子微生物学》的编辑已有十年之久，她是《遗传学年度评论》的主编，并在其他几个编辑委员会任职。她任职于NAS、NIH、Keck、Damon Runyon、Burroughs Wellcome、Jane Coffin Childs、HHMI、ASM和AAM拨款、奖学金、会议、教育和奖励审查小组。最重要的是，项目负责人积极参与实验室的指导工作。现有研究生8人，博士后4人，本科生4人，技术人员3人。在过去的15年中，她共指导了10名博士后，19名研究生和31名本科生。该项目由分子遗传学项目和分子与细胞生物科学部的细胞系统集群共同支持。