Intercellular Signaling in Vibrio Harveyi

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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.