Xavier, JoaoBoyle, Kerry2019-03-262019-03-272016https://hdl.handle.net/1813/64726Cooperation plays a key role in the lives of unicellular and multicellular organisms. However, the molecular mechanisms that stabilize cooperative behavior are still largely unknown. We use a model bacterial system of social behavior to investigate molecular mechanisms that regulate and stabilize cooperative traits. This model system is swarming motility in the opportunistic pathogen, Pseudomonas aeruginosa. Using this system in combination with computational techniques and quantitative systems biology approaches we studied the production dynamics of a public good, rhamnolipids. Through studying the native regulation of rhamnolipids synthesis in the wild-type strain of P. aeruginosa we found that quorum sensing signals are integrated with internal metabolic signals in a non-digital manner to determine the level of rhamnolipid synthesis gene expression. Starvation by different nutrients induced radically different expression patterns of the rhamnolipid synthesis operon rhlAB suggesting that the internal metabolic state of the cell plays a large role in determining the expression level of this cooperative trait. To further understand how metabolism affects the stability of cooperative behavior, we used experimental evolution in swarming colonies starting with an engineered metabolic mutant, which lacked the gene ?cbrA. This study revealed that cooperative behavior can be recovered after significant perturbation, but recovery to a stable cooperative state was associated with a metabolic profile distinct from the wild-type. As a whole this work supports that metabolism is intimately linked with the social behavior of an organism. The quantitative assays, computational models and data from this work provide a foundation for the continued investigation of the link between cooperative traits and metabolism in P. aeruginosa and other organisms.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalCooperationEvolutionMathematical ModelingPseudomonas aeruginosaRhamnolipidsSystems Biologydissertation or thesis