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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM065859-09
Application #
8258161
Study Section
Special Emphasis Panel (ZRG1-GGG-H (03))
Program Officer
Singh, Shiva P
Project Start
2002-08-01
Project End
2015-11-30
Budget Start
2012-01-15
Budget End
2012-11-30
Support Year
9
Fiscal Year
2012
Total Cost
$307,165
Indirect Cost
$114,115
Name
Princeton University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Perez, Lark J; Karagounis, Theodora K; Hurley, Amanda et al. (2014) Highly Potent, Chemically Stable Quorum Sensing Agonists for Vibrio Cholerae. Chem Sci 5:151-155
Ke, Xiaobo; Miller, Laura C; Ng, Wai-Leung et al. (2014) CqsA-CqsS quorum-sensing signal-receptor specificity in Photobacterium angustum. Mol Microbiol 91:821-33
Kim, Minyoung Kevin; Drescher, Knut; Pak, On Shun et al. (2014) Filaments in curved streamlines: Rapid formation of Staphylococcus aureus biofilm streamers. New J Phys 16:065024
Werner, Kristen M; Perez, Lark J; Ghosh, Rajarshi et al. (2014) Caenorhabditis elegans recognizes a bacterial quorum-sensing signal molecule through the AWCON neuron. J Biol Chem 289:26566-73
Shao, Yi; Bassler, Bonnie L (2014) Quorum regulatory small RNAs repress type VI secretion in Vibrio cholerae. Mol Microbiol 92:921-30
Drescher, Knut; Nadell, Carey D; Stone, Howard A et al. (2014) Solutions to the public goods dilemma in bacterial biofilms. Curr Biol 24:50-5
Shao, Yi; Feng, Lihui; Rutherford, Steven T et al. (2013) Functional determinants of the quorum-sensing non-coding RNAs and their roles in target regulation. EMBO J 32:2158-71
van Kessel, Julia C; Ulrich, Luke E; Zhulin, Igor B et al. (2013) Analysis of activator and repressor functions reveals the requirements for transcriptional control by LuxR, the master regulator of quorum sensing in Vibrio harveyi. MBio 4:
van Kessel, Julia C; Rutherford, Steven T; Shao, Yi et al. (2013) Individual and combined roles of the master regulators AphA and LuxR in control of the Vibrio harveyi quorum-sensing regulon. J Bacteriol 195:436-43
Nadell, Carey D; Bucci, Vanni; Drescher, Knut et al. (2013) Cutting through the complexity of cell collectives. Proc Biol Sci 280:20122770

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