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Programmed population control by cell-cell communication and regulated killing

You, Lingchong and Cox, Robert Sidney, III and Weiss, Ron and Arnold, Frances H. (2004) Programmed population control by cell-cell communication and regulated killing. Nature, 428 (6985). pp. 868-871. ISSN 0028-0836. doi:10.1038/nature02491.

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De novo engineering of gene circuits inside cells is extremely difficult, and efforts to realize predictable and robust performance must deal with noise in gene expression and variation in phenotypes between cells. 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, 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.

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Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2004 Nature Publishing Group. Received 18 January 2004; Accepted 15 March 2004; Published online 4 April 2004. Y. Wang, R. Georgescu, S. Thiberge, F. Balagadde and S. Maerkle assisted with preliminary characterization of the circuit. C. Collins constructed plasmids pLuxR, pLuxR2 and pluxGFPuv. We also thank Y. Yokobayashi, M. Raizada, J. Leadbetter, M. Elowitz and M. Savageau for discussions or comments on the manuscript. This material is based on work supported by the Defense Advanced Research Projects Agency (DARPA). Any opinions, findings, and conclusions or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of the DARPA.
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Defense Advanced Research Projects Agency (DARPA)UNSPECIFIED
Issue or Number:6985
Record Number:CaltechAUTHORS:20150327-140146311
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:56193
Deposited By: Tony Diaz
Deposited On:27 Mar 2015 21:15
Last Modified:10 Nov 2021 20:56

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