Bacterial cells are amongst the simplest forms of life. Nevertheless, explaining a cell’s behavior still represents a challenge that the scientific community is grappling with. In this dissertation, I disentangle multiple layers of interacting dynamic complex systems that govern the bacterial response including: 1) the metabolic network, 2) the genetic background, and 3) the nutritional environment. I start by implementing a traditional methodology for the deep metabolic characterization of a single strain of S. aureus, by reconstructing its metabolic network, and proceed to elucidate how this network governs its metabolic response as a result of a changing nutritional environment. Next, I leverage the deluge in genomic sequence data to propagate knowledge from deeply characterized Gram-negative strains including S. enterica to multiple closely related strains, linking genotypic variations to diverging phenotypes, and diverging phenotypes to bacterial lifestyle. Finally, I demonstrate how information inherent to small genomic deviations can reveal the impact of long term colonization on bacterial evolution.
|Advisor:||Palsson, Berhnard Ø.|
|Commitee:||Raffatellu, Manuela, Nizet, Victor, McCulloch, Andrew, Mesirov, Jill|
|School:||University of California, San Diego|
|School Location:||United States -- California|
|Source:||DAI-B 82/3(E), Dissertation Abstracts International|
|Subjects:||Bioinformatics, Genetics, Microbiology|
|Keywords:||Evolution, Metabolism, Prokaryotic pathogens, Systems biology|
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