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Programmed population control by cell–cell communication and regulated killing

Author

Listed:
  • Lingchong You

    (California Institute of Technology)

  • Robert Sidney Cox

    (California Institute of Technology)

  • Ron Weiss

    (Princeton University)

  • Frances H. Arnold

    (California Institute of Technology)

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.

Suggested Citation

  • Lingchong You & Robert Sidney Cox & Ron Weiss & Frances H. Arnold, 2004. "Programmed population control by cell–cell communication and regulated killing," Nature, Nature, vol. 428(6985), pages 868-871, April.
    • Handle: RePEc:nat:nature:v:428:y:2004:i:6985:d:10.1038_nature02491
    DOI: 10.1038/nature02491
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    Cited by:

    1. Anna-Maria Makri Pistikou & Glenn A. O. Cremers & Bryan L. Nathalia & Theodorus J. Meuleman & Bas W. A. Bögels & Bruno V. Eijkens & Anne Dreu & Maarten T. H. Bezembinder & Oscar M. J. A. Stassen & Car, 2023. "Engineering a scalable and orthogonal platform for synthetic communication in mammalian cells," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Keun-Young Kim & Jin Wang, 2007. "Potential Energy Landscape and Robustness of a Gene Regulatory Network: Toggle Switch," PLOS Computational Biology, Public Library of Science, vol. 3(3), pages 1-13, March.
    3. Chae Won Kang & Hyun Gyu Lim & Jaehyuk Won & Sanghak Cha & Giyoung Shin & Jae-Seong Yang & Jaeyoung Sung & Gyoo Yeol Jung, 2022. "Circuit-guided population acclimation of a synthetic microbial consortium for improved biochemical production," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    4. Zhaoshou Wang & Xin Wu & Jianghai Peng & Yidan Hu & Baishan Fang & Shiyang Huang, 2014. "Artificially Constructed Quorum-Sensing Circuits Are Used for Subtle Control of Bacterial Population Density," PLOS ONE, Public Library of Science, vol. 9(8), pages 1-7, August.
    5. Yu-Yu Cheng & Zhengyi Chen & Xinyun Cao & Tyler D. Ross & Tanya G. Falbel & Briana M. Burton & Ophelia S. Venturelli, 2023. "Programming bacteria for multiplexed DNA detection," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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