Journal article Open Access

Tunable genetic devices through simultaneous control of transcription and translation

Bartoli, Vittorio; Meaker, Grace A.; di Bernardo, Mario; Gorochowski, Thomas E.

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    <subfield code="u">School of Biosciences, Cardiff University, Museum Avenue, Cardiff, UK</subfield>
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    <subfield code="a">Meaker, Grace A.</subfield>
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    <subfield code="u">Department of Electrical Engineering and Information Technology, University of Naples Federico II, Via Claudio 21, Napoli, Italy</subfield>
    <subfield code="0">(orcid)0000-0002-3329-0839</subfield>
    <subfield code="a">di Bernardo, Mario</subfield>
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    <subfield code="u">BrisSynBio, University of Bristol, Life Sciences Building, Tyndall Avenue, Bristol, UK School of Biological Sciences, University of Bristol, Tyndall Avenue, Bristol, UK</subfield>
    <subfield code="0">(orcid)0000-0003-1702-786X</subfield>
    <subfield code="a">Gorochowski, Thomas E.</subfield>
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    <subfield code="u"> et al 2020 Nature.pdf</subfield>
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    <subfield code="c">2020-04-29</subfield>
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    <subfield code="p">Nature Communications</subfield>
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    <subfield code="u">BrisSynBio, University of Bristol, Life Sciences Building, Tyndall Avenue, Bristol, UK Department of Engineering Mathematics, University of Bristol, Woodland Road, Bristol, UK</subfield>
    <subfield code="0">(orcid)0000-0002-8764-1294</subfield>
    <subfield code="a">Bartoli, Vittorio</subfield>
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    <subfield code="a">Tunable genetic devices through simultaneous control of transcription and translation</subfield>
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    <subfield code="c">766840</subfield>
    <subfield code="a">Control Engineering of Biological Systems for Reliable Synthetic Biology Applications</subfield>
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    <subfield code="a">&lt;p&gt;&lt;strong&gt;Abstract&lt;/strong&gt;&lt;/p&gt;

&lt;p&gt;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 &amp;gt;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.&lt;/p&gt;</subfield>
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    <subfield code="a">10.1038/s41467-020-15653-7</subfield>
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