Programmed population control by cell–cell communication and regulated killing

Lingchong You, Robert Sidney Cox, Ron Weiss and Frances H. Arnold ()
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Lingchong You: California Institute of Technology
Robert Sidney Cox: California Institute of Technology
Ron Weiss: Princeton University
Frances H. Arnold: California Institute of Technology

Nature, 2004, vol. 428, issue 6985, 868-871

Abstract: Abstract De novo engineering of gene circuits inside cells is extremely difficult1,2,3,4,5,6,7,8,9, and efforts to realize predictable and robust performance must deal with noise in gene expression and variation in phenotypes between cells10,11,12. 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 system13,14, 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.

Date: 2004
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DOI: 10.1038/nature02491

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