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Multidimensional Characterization of Parts Enhances Modeling Accuracy in Genetic Circuits

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    Multidimensional Characterization of Parts Enhances Modeling Accuracy in Genetic Circuits
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    • Mariana Gómez-Schiavon
      Mariana Gómez-Schiavon
      Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, United States
      More by Mariana Gómez-Schiavon
      Orcidhttp://orcid.org/0000-0002-0955-7257
    • Galen Dods
      Galen Dods
      Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, United States
      More by Galen Dods
    • Hana El-Samad*
      Hana El-Samad
      Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, United States
      Chan−Zuckerberg Biohub, San Francisco, California 94158, United States
      Cell Design Institute, University of California, San Francisco, San Francisco, California 94158, United States
      *Email: [email protected]
      More by Hana El-Samad
      Orcidhttp://orcid.org/0000-0001-6239-9916
    • Andrew H. Ng*
      Andrew H. Ng
      Cell Design Institute, University of California, San Francisco, San Francisco, California 94158, United States
      Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California 94158, United States
      *Email: [email protected]
      More by Andrew H. Ng
      Orcidhttp://orcid.org/0000-0001-8044-1807
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    ACS Synthetic Biology

    Cite this: ACS Synth. Biol. 2020, 9, 11, 2917–2926
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    https://doi.org/10.1021/acssynbio.0c00288
    Published November 9, 2020
    Copyright © 2020 American Chemical Society
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    Abstract

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    Mathematical models can aid the design of genetic circuits, but may yield inaccurate results if individual parts are not modeled at the appropriate resolution. To illustrate the importance of this concept, we study transcriptional cascades consisting of two inducible synthetic transcription factors connected in series. Despite the simplicity of this design, we find that accurate prediction of circuit behavior requires mapping the dose responses of each circuit component along the dimensions of both its expression level and its inducer concentration. Using this multidimensional characterization, we were able to computationally explore the behavior of 16 different circuit designs. We experimentally verified a subset of these predictions and found substantial agreement. This method of biological part characterization enables the use of models to identify (un)desired circuit behaviors prior to experimental implementation, thus shortening the design–build–test cycle for more complex circuits.

    Copyright © 2020 American Chemical Society

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acssynbio.0c00288.

    • Supplemental figures; plasmids, oligos, and strains used; pZ4 (-Gal4 site) sequence (PDF)

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    Cited By

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    This article is cited by 13 publications.

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    ACS Synthetic Biology

    Cite this: ACS Synth. Biol. 2020, 9, 11, 2917–2926
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acssynbio.0c00288
    Published November 9, 2020
    Copyright © 2020 American Chemical Society
    Request reuse permissions

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