Programmed population control by cell–cell communication and regulated killing

Abstract

De novo engineering of gene circuits inside cells is extremely difficult^{1,2,3,4,5,6,7,8,9}, and efforts to realize predictable and robust performance must deal with noise in gene expression and variation in phenotypes between cells^10,11,12. Here we demonstrate that by coupling gene expression to cell survival and death using cell–cell communication, we can programme the dynamics of a population despite variability in the behaviour of individual cells. Specifically, we have built and characterized a ‘population control’ circuit that autonomously regulates the density of an Escherichia coli population. The cell density is broadcasted and detected by elements from a bacterial quorum-sensing system^13,14, which in turn regulate the death rate. As predicted by a simple mathematical model, the circuit can set a stable steady state in terms of cell density and gene expression that is easily tunable by varying the stability of the cell–cell communication signal. This circuit incorporates a mechanism for programmed death in response to changes in the environment, and allows us to probe the design principles of its more complex natural counterparts.