Genome-based Modeling and Design of Microbial 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. Advances in genome sequencing and omics methods have enabled the unprecedented characterization of cellular metabolism and have paved the way for developing genome-scale metabolic models. While such genome-scale modeling methods have been extensively applied to studying metabolism in industrially relevant microbes such as Escherichia coli, there are relatively few models of bacteria relevant to gut microbiome and even fewer models of microbial communities. Hence, one of the longer term objectives of our research is to develop integrated models of human metabolism and genome-scale models of microbes relevant to the gut. Specifically, in the shorter term, we will focus on developing models of the microbes present in gut microbiome and common probiotics and integrate them into a community model in order to simulate the dynamics of community in response to dietary changes.The successful completion of the proposal will enable the development of novel tools for modeling and engineering metabolism in individual cells and communities and lead to 1) robust microbial communities for non-natural chemical production and 2) potential nutritional strategies for maintaining a healthy gut microbiome. Further, the computational and experimental tools developed will provide the foundations for improved understanding and engineering of metabolism in complex environments and will drive the application to other significant problems including bioconversion of CO2 to value-added chemicals, bioremediation and personalized nutrition and medicine.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.