Quantitative Analysis of Metabolic Networks and Flux Dynamics in Thermophilic Bacteria

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Thermus thermophilus is a potential host bacterium for the production of biofuels and other useful biochemicals. However, relatively little is known about its metabolism and the regulation of its metabolic activity. This project will characterize the metabolic network of this organism and quantify its metabolic flux phenotypes using classical steady-state techniques. In addition, techniques will be developed for dynamic metabolic flux analysis and metabolic network elucidation, requiring new tools and methods based on 13C-isotopomer analysis and tandem mass spectrometry. This project will 1) develop a new method of dynamic metabolic flux analysis, 2) provide improved techniques for validating metabolic network models, and 3) define optimized growth conditions for T. thermophilus. Broader Impacts: This project promises a major step forward in metabolic network analysis that will be broadly applicable to many organisms of biotechnological and biomedical importance. In addition, this project provides unique opportunities for graduate and undergraduate student education and training in an interdisciplinary environment comprising computational and experimental biology, metabolic flux analysis, mass spectrometry and metabolic network modeling.