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Harnessing the central dogma for stringent multi-level control of gene expression

Author

Listed:
  • F. Veronica Greco

    (University of Bristol)

  • Amir Pandi

    (Max Planck Institute for Terrestrial Microbiology)

  • Tobias J. Erb

    (Max Planck Institute for Terrestrial Microbiology
    SYNMIKRO Center of Synthetic Microbiology)

  • Claire S. Grierson

    (University of Bristol
    University of Bristol)

  • Thomas E. Gorochowski

    (University of Bristol
    University of Bristol)

Abstract

Strictly controlled inducible gene expression is crucial when engineering biological systems where even tiny amounts of a protein have a large impact on function or host cell viability. In these cases, leaky protein production must be avoided, but without affecting the achievable range of expression. Here, we demonstrate how the central dogma offers a simple solution to this challenge. By simultaneously regulating transcription and translation, we show how basal expression of an inducible system can be reduced, with little impact on the maximum expression rate. Using this approach, we create several stringent expression systems displaying >1000-fold change in their output after induction and show how multi-level regulation can suppress transcriptional noise and create digital-like switches between ‘on’ and ‘off’ states. These tools will aid those working with toxic genes or requiring precise regulation and propagation of cellular signals, plus illustrate the value of more diverse regulatory designs for synthetic biology.

Suggested Citation

  • F. Veronica Greco & Amir Pandi & Tobias J. Erb & Claire S. Grierson & Thomas E. Gorochowski, 2021. "Harnessing the central dogma for stringent multi-level control of gene expression," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21995-7
    DOI: 10.1038/s41467-021-21995-7
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    Cited by:

    1. Shivang Hina-Nilesh Joshi & Chentao Yong & Andras Gyorgy, 2022. "Inducible plasmid copy number control for synthetic biology in commonly used E. coli strains," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Carolyn N. Bayer & Maja Rennig & Anja K. Ehrmann & Morten H. H. Nørholm, 2021. "A standardized genome architecture for bacterial synthetic biology (SEGA)," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    3. Amir Pandi & Christoph Diehl & Ali Yazdizadeh Kharrazi & Scott A. Scholz & Elizaveta Bobkova & Léon Faure & Maren Nattermann & David Adam & Nils Chapin & Yeganeh Foroughijabbari & Charles Moritz & Nic, 2022. "A versatile active learning workflow for optimization of genetic and metabolic networks," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Michael B. Sheets & Nathan Tague & Mary J. Dunlop, 2023. "An optogenetic toolkit for light-inducible antibiotic resistance," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    5. Yuanli Gao & Lei Wang & Baojun Wang, 2023. "Customizing cellular signal processing by synthetic multi-level regulatory circuits," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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