EAGER: Dynamic Flux Control Enabled by Synthetic Metabolic Valves

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This EAGER project, funded by the Systems and Synthetic Biology program in MCB and the Energy for Sustainability program, will lead to the development of new tools that will enable investigators to control the allocation of carbon, energy, and other resources in cells in a precise way during the biomanufacture of chemicals. This will allow carbon and energy to be diverted from cell growth to product formation, which should increase product yield. In addition, the tools could be transferred from bacteria used in biomanufacturing to other organisms, and used to address fundamental questions about control and regulation of metabolism in these systems. The investigator will train graduate and undergraduate students in an interdisciplinary environment and mentor undergraduates who participate in the International Genetically Engineering Machine (iGEM) competition, an international competition that engages young people in science and engineering by asking them to design and build new function into microorganisms.Technical Description: This project aims to develop flexible (controllable) valves in metabolic pathways that will allow carbon flux through pathways to be redirected at will. This would enable the dynamic optimization of microbial metabolism, shifting metabolic flux from pathways associated with growth to those associated with product formation. Researchers will use CRISPRi gene silencing technologies coupled with controlled enzyme degradation to achieve the desired carbon flux. The researchers will then test the effectiveness of these strategies thru detailed metabolic flux measurements. The tools could not only improve current metabolic engineering and synthetic biology practices, and thus impact biomanufacturing of renewable chemicals, but if transferable to other hosts, the technology could be used to address important questions about regulation of metabolism and metabolic pathways.