Using populations of engineered cells to regulate extracellular chemical concentrations

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Jordan Ang, David McMillen, Karen Polizzi, Guy-Bart Stan

Imperial College London, United Kingdom

We are working to construct a synthetic gene network intended to allow a population of engineered yeast cells to actively regulate the extracellular concentration of a small molecule. To accomplish this, the cells will be equipped with both the ability to sense the extracellular concentration level of the molecule, as well as the ability to synthesize and secrete the molecule itself. An intercellular control circuit coupling sensing to biochemical synthesis will effectively couple the cell population’s overall secretion rate to the extracellular small molecule concentration. Basing the control circuit design around the strategies of integral control will permit for the secretion rate to change precisely in response to static perturbations to the extracellular concentration. Furthermore, built-in modularity within the design–specifically the ability for the control circuit to interface with different sensing and synthesis units–is intended to allow for future customization toward different molecules of interest.