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Automated optogenetic feedback control for precise and robust regulation of gene expression and cell growth

Author

Listed:
  • Andreas Milias-Argeitis

    (ETH Zurich)

  • Marc Rullan

    (ETH Zurich)

  • Stephanie K. Aoki

    (ETH Zurich)

  • Peter Buchmann

    (ETH Zurich)

  • Mustafa Khammash

    (ETH Zurich)

Abstract

Dynamic control of gene expression can have far-reaching implications for biotechnological applications and biological discovery. Thanks to the advantages of light, optogenetics has emerged as an ideal technology for this task. Current state-of-the-art methods for optical expression control fail to combine precision with repeatability and cannot withstand changing operating culture conditions. Here, we present a novel fully automatic experimental platform for the robust and precise long-term optogenetic regulation of protein production in liquid Escherichia coli cultures. Using a computer-controlled light-responsive two-component system, we accurately track prescribed dynamic green fluorescent protein expression profiles through the application of feedback control, and show that the system adapts to global perturbations such as nutrient and temperature changes. We demonstrate the efficacy and potential utility of our approach by placing a key metabolic enzyme under optogenetic control, thus enabling dynamic regulation of the culture growth rate with potential applications in bacterial physiology studies and biotechnology.

Suggested Citation

  • Andreas Milias-Argeitis & Marc Rullan & Stephanie K. Aoki & Peter Buchmann & Mustafa Khammash, 2016. "Automated optogenetic feedback control for precise and robust regulation of gene expression and cell growth," Nature Communications, Nature, vol. 7(1), pages 1-11, November.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12546
    DOI: 10.1038/ncomms12546
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    Cited by:

    1. François Bertaux & Sebastián Sosa-Carrillo & Viktoriia Gross & Achille Fraisse & Chetan Aditya & Mariela Furstenheim & Gregory Batt, 2022. "Enhancing bioreactor arrays for automated measurements and reactive control with ReacSight," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Joaquín Gutiérrez Mena & Sant Kumar & Mustafa Khammash, 2022. "Dynamic cybergenetic control of bacterial co-culture composition via optogenetic feedback," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Maurice Filo & Sant Kumar & Mustafa Khammash, 2022. "A hierarchy of biomolecular proportional-integral-derivative feedback controllers for robust perfect adaptation and dynamic performance," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    4. Sally Wang & Chen-Yu Chen & John R. Rzasa & Chen-Yu Tsao & Jinyang Li & Eric VanArsdale & Eunkyoung Kim & Fauziah Rahma Zakaria & Gregory F. Payne & William E. Bentley, 2023. "Redox-enabled electronic interrogation and feedback control of hierarchical and networked biological systems," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Jean-Baptiste Lugagne & Caroline M. Blassick & Mary J. Dunlop, 2024. "Deep model predictive control of gene expression in thousands of single cells," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    6. Anđela Davidović & Remy Chait & Gregory Batt & Jakob Ruess, 2022. "Parameter inference for stochastic biochemical models from perturbation experiments parallelised at the single cell level," PLOS Computational Biology, Public Library of Science, vol. 18(3), pages 1-22, March.
    7. Sebastián Sosa-Carrillo & Henri Galez & Sara Napolitano & François Bertaux & Gregory Batt, 2023. "Maximizing protein production by keeping cells at optimal secretory stress levels using real-time control approaches," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Lucas Henrion & Juan Andres Martinez & Vincent Vandenbroucke & Mathéo Delvenne & Samuel Telek & Andrew Zicler & Alexander Grünberger & Frank Delvigne, 2023. "Fitness cost associated with cell phenotypic switching drives population diversification dynamics and controllability," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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