Cooperative Control of Bacterial Consortia with Application to a Wound-Healing Model System

Wound healing is a complicated biological process consisting of many types of cellular dynamics and functions regulated by chemical molecular signals. Recent advances in synthetic biology have made it possible to predictably design and build closed-loop controllers that can function appropriately alongside biological species. In this work we develop a simple dynamical population model mimicking the sequential relay-like dynamics of cellular populations involved in the wound healing process. Our model consists of four nodes and fives signals whose parameters we can tune to simulate various chronic healing conditions. We also develop a set of regulator functions based on type-1 incoherent feed forward loops (IFFL) that can sense the change from acute healing to incomplete chronic wounds, improving the undesired system dynamics in a timely manner. Both wound healing and type-1 IFFL controller architectures are compatible with available synthetic biology experimental tools for potential medical application. We began implementing the population circuits in wild type E. coli strain to build a wound healing testbed model. We will experimentally characterize the improved wound healing functions of our chronic-like wound healing testbed, regulated by our type-1 IFFL regulator controller cell types.