Analysis of Circuits for Dosage Control in Microbial Populations

Abstract

Designing genetic circuits to control the behaviors of microbial populations is an ongoing challenge in synthetic biology. Here we analyze circuits which implement dosage control by controlling levels of a global signal in a microbial population in face of varying cell density, growth rate, and environmental dilution. We utilize the Lux quorum sensing system to implement dosage control circuits, and we analyze the dynamics of circuits using both simplified analytical analysis and in silico simulations. We demonstrate that strong negative feedback through inhibiting LuxI synthase expression along with AiiA degradase activity results in circuits with fast response times and robustness to cell density and dilution rate. We find that degradase activity yields robustness to variations in population density for large population sizes, while negative feedback to synthase production decreases sensitivity to dilution rates.