Model-based Engineering of Metabolism in Microbial Cells and Communities

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Metabolism is the source of energy required for powering cellular processes in all living things. Understanding metabolism in an integrated way allows the opportunity to harness the power of natural metabolic networks for several applications including the manufacture of renewable fuels and non-natural chemicals, clean-up of contaminated groundwater, and potentially for maintaining a healthy gut microbiome through nutritional and probiotic interventions. However, there are several challenges in engineering metabolism for these practical applications. A key limitation is the ability to quantitatively describe the dynamics of metabolic transience within the cells and the metabolic interactions with other species in microbial communities. Further, novel tools to manipulate metabolism in a dynamic manner will enable the precise engineering of metabolism. Hence, the objectives of the proposal are the development of modeling and optimization frameworks for large-scale metabolic networks in cells and communities along with experimental tools for the dynamic control of metabolic pathways. The ultimate objective is the application of these tools for the development of commercializable bioprocess for the manufacture of non-natural chemicals and model-based design for personalized nutrition and medicine.