Intercellular Signaling in Vibrio Harveyi

智力优势：这个项目的总体目标是了解群体感应：细菌中细胞间通讯的过程。群体感应包括产生、释放和随后检测称为自诱导物的化学信号分子。这一过程使细菌群体能够在整个社区范围内调节基因表达，从而调节行为。产生并同时检测多个自身诱导物的能力首先在哈氏弧菌中发现，并且在哈氏弧菌中得到最好的研究，哈氏弧菌使用三个自身诱导物用于种内、属内和种间细胞-细胞通信。因此，哈维氏弧菌群体感应回路非常适合探索有关感觉信息如何整合和转导以控制基因表达的问题。该项目的研究重点是五个非编码小RNA（sRNA），它们位于哈维氏弧菌群体感应电路的核心，负责收集自诱导物输入信息并将其转换为群体感应输出响应。控制单个sRNA的因素和机制将被定义，每个sRNA的个体和集体靶标将被鉴定，并且将发现由sRNA调节剂（与DNA结合蛋白相反）提供的独特控制特征。在最一般的水平上，该项目将提供深入了解物种内和物种间的通信，人口水平的合作，以及在细胞水平上的信号转导和信息处理的网络原则。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，细菌中的全球性质一直未得到充分的重视和研究。最后，在实践层面上，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讲座和实验室课程（MOL 101：从DNA到人类复杂性）和专业的门户分子生物学课程（MOL 214：分子生物学导论）。此外，项目负责人是分子生物学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。她还指导该部的科学推广工作。她是普林斯顿大学科学技术理事会主任，负责开发、实施和审查所有非科学专业的科学、数学和工程课程。她是美国微生物学会的当选主席。她是霍华德休斯2009年假期讲师，并在该能力，她负责开发一系列讲座和活动，为高中学生的生物多样性和无形的细菌世界将被制成10万张DVD，并免费提供给美国高中教师课堂使用。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，包括旅游舞蹈作品凶猛的美丽基因组和在巴尔的摩科学中心（细胞：我们体内的宇宙）的永久展览。她是斯隆基金会的评审团成员，负责评估和资助与科学相关的剧本。除其他职责外，她一直是分子微生物学编辑十年，她是遗传学年度评论的主编，她是其他几个编辑委员会。她在NAS、NIH、Keck、Damon Runyon、Burroughs Wellcome、Jane Coffin查尔兹、HHMI、ASM和AAM资助、奖学金、会议、教育和奖项评审小组任职。最重要的是，项目负责人积极参与实验室的指导。她目前有8名研究生，4名博士后，4名本科生和3名技术人员。在过去的15年里，她指导了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计划和分子和细胞生物科学部的细胞系统集群共同支持。

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.