Modeling of Purine/Histidine/Thiamine Pathway

Abstract

Current efforts to understand physiology as a complex system are comprised of modeling metabolic networks, reconstructing pathway systems and predicting robustness from genomic sequences. Detailed kinetic knowledge of biochemistry and metabolism, gained over several decades, provides the basis on which these global approaches have been built. Nonetheless, a fundamental question in biology remains: How are metabolic pathways integrated and regulated to ensure the amazingly robust and efficient physiology that is associated with a living cell? For over 20 years, the research in Dr. Diana M. Downs’ laboratory at the University of Georgia (DMD Lab) in collaboration with two other laboratories has contributed insights into metabolic components and connections, using a bacterial model system, high-throughput metabolomics, and computational approaches, respectively. The present application proposes to build on past successes, utilize state-of-the-art metabolomics techniques, integrate kinetic and metabolomics data with computational models, and generate insights into the structure and function of a specific metabolic network in Salmonella enterica and how it responds to perturbations.