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 #
5R01GM065859-11
Application #
8585857
Study Section
Special Emphasis Panel (ZRG1-GGG-H (03))
Program Officer
Sledjeski, Darren D
Project Start
2002-08-01
Project End
2015-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
11
Fiscal Year
2014
Total Cost
$330,354
Indirect Cost
$117,671
Name
Princeton University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Ismail, Anisa S; Valastyan, Julie S; Bassler, Bonnie L (2016) A Host-Produced Autoinducer-2 Mimic Activates Bacterial Quorum Sensing. Cell Host Microbe 19:470-80
Papenfort, Kai; Bassler, Bonnie L (2016) Quorum sensing signal-response systems in Gram-negative bacteria. Nat Rev Microbiol 14:576-88
Drescher, Knut; Dunkel, Jörn; Nadell, Carey D et al. (2016) Architectural transitions in Vibrio cholerae biofilms at single-cell resolution. Proc Natl Acad Sci U S A 113:E2066-72
Even-Tov, Eran; Bendori, Shira Omer; Valastyan, Julie et al. (2016) Social Evolution Selects for Redundancy in Bacterial Quorum Sensing. PLoS Biol 14:e1002386
Kim, Minyoung Kevin; Ingremeau, François; Zhao, Aishan et al. (2016) Local and global consequences of flow on bacterial quorum sensing. Nat Microbiol 1:15005
Yan, Jing; Sharo, Andrew G; Stone, Howard A et al. (2016) Vibrio cholerae biofilm growth program and architecture revealed by single-cell live imaging. Proc Natl Acad Sci U S A 113:E5337-43
Persat, Alexandre; Nadell, Carey D; Kim, Minyoung Kevin et al. (2015) The mechanical world of bacteria. Cell 161:988-97
Ke, Xiaobo; Miller, Laura C; Bassler, Bonnie L (2015) Determinants governing ligand specificity of the Vibrio harveyi LuxN quorum-sensing receptor. Mol Microbiol 95:127-42
van Kessel, Julia C; Rutherford, Steven T; Cong, Jian-Ping et al. (2015) Quorum sensing regulates the osmotic stress response in Vibrio harveyi. J Bacteriol 197:73-80
Feng, Lihui; Rutherford, Steven T; Papenfort, Kai et al. (2015) A qrr noncoding RNA deploys four different regulatory mechanisms to optimize quorum-sensing dynamics. Cell 160:228-40

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