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
Kim, Minyoung Kevin; Zhao, Aishan; Wang, Ashley et al. (2017) Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development. Nat Microbiol 2:17080
Paczkowski, Jon E; Mukherjee, Sampriti; McCready, Amelia R et al. (2017) Flavonoids Suppress Pseudomonas aeruginosa Virulence through Allosteric Inhibition of Quorum-sensing Receptors. J Biol Chem 292:4064-4076
H√łyland-Kroghsbo, Nina M; Paczkowski, Jon; Mukherjee, Sampriti et al. (2017) Quorum sensing controls the Pseudomonas aeruginosa CRISPR-Cas adaptive immune system. Proc Natl Acad Sci U S A 114:131-135
Nadell, Carey D; Ricaurte, Deirdre; Yan, Jing et al. (2017) Flow environment and matrix structure interact to determine spatial competition in Pseudomonas aeruginosa biofilms. Elife 6:
Papenfort, Kai; Silpe, Justin E; Schramma, Kelsey R et al. (2017) A Vibrio cholerae autoinducer-receptor pair that controls biofilm formation. Nat Chem Biol 13:551-557
Mukherjee, Sampriti; Moustafa, Dina; Smith, Chari D et al. (2017) The RhlR quorum-sensing receptor controls Pseudomonas aeruginosa pathogenesis and biofilm development independently of its canonical homoserine lactone autoinducer. PLoS Pathog 13:e1006504
Yan, Jing; Nadell, Carey D; Bassler, Bonnie L (2017) Environmental fluctuation governs selection for plasticity in biofilm production. ISME J 11:1569-1577
Yan, Jing; Nadell, Carey D; Stone, Howard A et al. (2017) Extracellular-matrix-mediated osmotic pressure drives Vibrio cholerae biofilm expansion and cheater exclusion. Nat Commun 8:327
Hurley, Amanda; Bassler, Bonnie L (2017) Asymmetric regulation of quorum-sensing receptors drives autoinducer-specific gene expression programs in Vibrio cholerae. PLoS Genet 13:e1006826
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

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