Trade-offs in Robustness to Perturbations of Bacterial Population Controllers

Synthetic biology applications have the potential to have lasting impact; however, there is considerable difficulty in scaling up engineered genetic circuits. One of the current hurdles is resource sharing, where different circuit components become implicitly coupled through the host cell9s pool of resources, which may destroy circuit function. One potential solution around this problem is to distribute genetic circuit components across multiple cell strains and control the cell population size using a population controller. In these situations, perturbations in the availability of cellular resources, such as due to resource sharing, will affect the performance of the population controller. In this work, we model a genetic population controller implemented by a genetic circuit while considering perturbations in the availability of cellular resources. We analyze how these intracellular perturbations and extracellular disturbances to cell growth affect cell population size. We find that it is not possible to tune the population controller9s gain such that the population density is robust to both extracellular disturbances and perturbations to the pool of available resources.