Many biological functions are cooperative in nature and depend on interactions, both physical and chemical, between cells. This project will investigate the organizing principles of multicellular assemblies using systems biology approaches and the social bacterium Pseudomonas aeruginosa as a model. This project will test the hypothesis that social bacteria have evolved molecular mechanisms that confer robustness to their multicellular traits. Multidisciplinary approaches that combine mathematical modeling, microbial genetics and comparative genomics will be used to dissect the multiple factors that affect biofilm formation and swarming motility. Graduate student training includes extensive research experience in genomic and systems biology. Education outreach programs will train summer undergraduate student interns and local scientific community workshop participants in evolutionary genomics and systems biology analyses including the use of computational tools. The outreach program is partnered with Hunter College of the City University of New York, a neighboring large, urban, and public institution.

This project will use swarming as a model of microbial cooperation. Swarming is a collective form of surface motility that enables bacteria to migrate over surfaces. Swarming requires the production and secretion of rhamnolipid biosurfactants by individual bacteria: biosurfactant production requires significant resources that can be exploited by cheaters who do not produce the surfactant but take advantage of surfactant production by others. Cooperative behavior can also be disrupted by mutants with many flagella that take over the population and disrupt swarming at the cost of being unable to form biofilms. This project will: 1) dissect the spatial-temporal dynamics of metabolic prudence, a mechanism regulating the synthesis of rhamnolipids required for swarming; 2) investigate the evolutionary and molecular mechanisms of hyperswarming evolution; and 3) dissect the trade-off between two collective traits: swarming and biofilms in natural bacterial populations. In addition this project will develop a bioinformatics infrastructure and database to investigate the genomic correlates of phenotypic diversity in environmental strains of P. aeruginosa. Specifically, this project will develop novel methods of comparative genomics based on evolutionary analysis of whole genome sequencing data using ancestral character reconstruction of both genotypes and phenotypes. The novel methods will be applicable to other social bacteria.

Agency
National Science Foundation (NSF)
Institute
Division of Molecular and Cellular Biosciences (MCB)
Type
Standard Grant (Standard)
Application #
1517002
Program Officer
David Rockcliffe
Project Start
Project End
Budget Start
2015-08-15
Budget End
2019-07-31
Support Year
Fiscal Year
2015
Total Cost
$887,516
Indirect Cost
Name
Sloan Kettering Institute for Cancer Research
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10065