|Awardee:||UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.|
|Doing Business As Name:||University of Georgia Research Foundation Inc|
|Estimated Total Award Amount:||$ 299,996|
|Funds Obligated to Date:||
|Awarding Agency Code:||4900|
|Funding Agency Code:||4900|
|Primary Program Source:||040100 NSF RESEARCH & RELATED ACTIVIT|
|Award Title or Description:||Probing the Metabolic Network in Salmonella and its Response to Perturbations|
|Federal Award ID Number:||1411672|
|Program:||Systems and Synthetic Biology|
|Street:||310 East Campus Rd|
|Awardee Cong. District:||10|
Primary Place of Performance
|Organization Name:||University of Georgia|
|Street:||200 D.W. Brooks Drive|
Abstract at Time of Award
A fundamental question in biology is how metabolic pathways are integrated to result in the robust and efficient physiology characteristic of living cells. Current efforts to understand physiology as a complex system are comprised of modeling and reconstructing metabolic networks, and predicting their robustness from genomic sequences. Fundamental knowledge of biochemistry and metabolism, gained over several decades, provides the basis on which these global approaches are built. The proposed research focuses on integrating quantitative analysis into the study of a metabolism. Toward this end, investigators with diverse expertise will work together to quantify the metabolites of the system to assess the effect of specific perturbations; generate mathematical models from the metabolomic data; and iteratively test these models using genetic and biochemical approaches. This collaborative effort is anticipated to generate novel insights into the complexity and dynamics of integrated metabolic networks. The proposed work is a collaboration between a microbial physiologist, a systems biologist with expertise in modeling and predicting metabolic networks, and a synthetic chemist with expertise in metabolomics. The team will utilize state-of-the-art techniques to define the integrated metabolic network of purine, histidine, and thiamine biosynthesis of Salmonella. A key focus is on a strain that lacks the purH gene, which results in the accumulation of the aminoimidazole carboxamide ribotide intermediate metabolite. This mutation reveals the unpredicted metabolic connections between the purine, histidine and thiamine metabolic networks. The accumulation of this metabolite in other organisms, including mammalian systems, is the basis for a number of severe hereditary disorders. The project will train students and postdoctoral fellows at the intersection of biology, mathematics, chemistry and computation, and hence, will lead to a highly skilled next-generation workforce. The investigators have a track record of training minority students.
Publications Produced as a Result of this Research
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92. Bazurto, J. V., K. R. Farley and D. M. Downs. "An unexpected route to an essential cofactor: Escherichia coli relies on threonine for thiamine biosynthesis." mBio, v.7, 2016, p.. doi:10.1128/mBio.01840-15
Bazurto JV, Heitman NJ, Downs DM "Aminoimidazole Carboxamide Ribotide Exerts Opposing Effects on Thiamine Synthesis in Salmonella enterica." Journal of Bacteriology, v.197, 2015, p.2821. doi:10.1128/JB.00282-15
Dolatshahi, S., and E.O. Voit "Identification of metabolic pathway systems" Frontiers in Genetics, v.7, 2016, p.. doi:10.3389/fgene.2016.00006
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