(498e) Circuit-Host Interactions: Mechanism and Control

Failure of modularity remains a significant challenge for assembling synthetic gene circuits with tested modules as they often do not function as expected. Hidden circuit-host interactions, such as growth feedback and resource competition, could significantly impair intended circuit function but are often overlooked. Here, I will present our recent efforts on the quantitative understanding of how the functional perturbation of gene circuits by these hidden interactions depends on network topology, host physiological environment, and resource competition, together with modeling frameworks for predicting circuit behaviors and practical control strategies for engineering robust gene circuits. First, we will discuss how the interference of synthetic gene circuit function by growth feedback depends on circuit network topology and nutrient level. Second, we will demonstrate how resource competition redirected desired successive cell fate transitions following a ‘winner-takes-all’ rule. Third, we will highlight our control strategies against resource competition, including a division of labor using microbial consortia, negatively competitive regulation (NCR) controllers. Lastly, we will discuss the effects of resource competition on the circuit noise behavior. Overall, our works will help us in the understanding and control of circuit-host interactions toward engineering robust synthetic gene circuits