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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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  <identifier identifierType="URL">https://zenodo.org/record/4818306</identifier>
  <creators>
    <creator>
      <creatorName>Bartoli, Vittorio</creatorName>
      <givenName>Vittorio</givenName>
      <familyName>Bartoli</familyName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0002-8764-1294</nameIdentifier>
      <affiliation>BrisSynBio, University of Bristol, Life Sciences Building, Tyndall Avenue, Bristol, UK Department of Engineering Mathematics, University of Bristol, Woodland Road, Bristol, UK</affiliation>
    </creator>
    <creator>
      <creatorName>Meaker, Grace A.</creatorName>
      <givenName>Grace A.</givenName>
      <familyName>Meaker</familyName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0003-4705-3137</nameIdentifier>
      <affiliation>School of Biosciences, Cardiff University, Museum Avenue, Cardiff, UK</affiliation>
    </creator>
    <creator>
      <creatorName>di Bernardo, Mario</creatorName>
      <givenName>Mario</givenName>
      <familyName>di Bernardo</familyName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0002-3329-0839</nameIdentifier>
      <affiliation>Department of Electrical Engineering and Information Technology, University of Naples Federico II, Via Claudio 21, Napoli, Italy</affiliation>
    </creator>
    <creator>
      <creatorName>Gorochowski, Thomas E.</creatorName>
      <givenName>Thomas E.</givenName>
      <familyName>Gorochowski</familyName>
      <nameIdentifier nameIdentifierScheme="ORCID" schemeURI="http://orcid.org/">0000-0003-1702-786X</nameIdentifier>
      <affiliation>BrisSynBio, University of Bristol, Life Sciences Building, Tyndall Avenue, Bristol, UK School of Biological Sciences, University of Bristol, Tyndall Avenue, Bristol, UK</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Tunable genetic devices through simultaneous control of transcription and translation</title>
  </titles>
  <publisher>Zenodo</publisher>
  <publicationYear>2020</publicationYear>
  <dates>
    <date dateType="Issued">2020-04-29</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://zenodo.org/record/4818306</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1038/s41467-020-15653-7</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://zenodo.org/communities/cosy-bio</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="https://creativecommons.org/licenses/by/4.0/legalcode">Creative Commons Attribution 4.0 International</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">&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;</description>
  </descriptions>
  <fundingReferences>
    <fundingReference>
      <funderName>European Commission</funderName>
      <funderIdentifier funderIdentifierType="Crossref Funder ID">10.13039/501100000780</funderIdentifier>
      <awardNumber awardURI="info:eu-repo/grantAgreement/EC/H2020/766840/">766840</awardNumber>
      <awardTitle>Control Engineering of Biological Systems for Reliable Synthetic Biology Applications</awardTitle>
    </fundingReference>
  </fundingReferences>
</resource>
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