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Tunable genetic devices through simultaneous control of transcription and translation

Author

Listed:
  • Vittorio Bartoli

    (University of Bristol, Life Sciences Building
    University of Bristol)

  • Grace A. Meaker

    (Cardiff University)

  • Mario di Bernardo

    (University of Bristol, Life Sciences Building
    University of Bristol
    University of Naples Federico II)

  • Thomas E. Gorochowski

    (University of Bristol, Life Sciences Building
    University of Bristol)

Abstract

Synthetic genetic circuits allow us to modify the behavior of living cells. However, changes in environmental conditions and unforeseen interactions with the host cell can cause deviations from a desired function, resulting in the need for time-consuming reassembly to fix these issues. Here, we use a regulatory motif that controls transcription and translation to create genetic devices whose response functions can be dynamically tuned. This allows us, after construction, to shift the on and off states of a sensor by 4.5- and 28-fold, respectively, and modify genetic NOT and NOR logic gates to allow their transitions between states to be varied over a >6-fold range. In all cases, tuning leads to trade-offs in the fold-change and the ability to distinguish cellular states. This work lays the foundation for adaptive genetic circuits that can be tuned after their physical assembly to maintain functionality across diverse environments and design contexts.

Suggested Citation

  • Vittorio Bartoli & Grace A. Meaker & Mario di Bernardo & Thomas E. Gorochowski, 2020. "Tunable genetic devices through simultaneous control of transcription and translation," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15653-7
    DOI: 10.1038/s41467-020-15653-7
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    Cited by:

    1. Judee A. Sharon & Chelsea Dasrath & Aiden Fujiwara & Alessandro Snyder & Mace Blank & Sam O’Brien & Lauren M. Aufdembrink & Aaron E. Engelhart & Katarzyna P. Adamala, 2023. "Trumpet is an operating system for simple and robust cell-free biocomputing," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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