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An Orthogonal Multi-input Integration System to Control Gene Expression in Escherichia coli

Research output: Contribution to journalLetter

Original languageEnglish
Pages (from-to)1816-1824
Number of pages9
JournalACS Synthetic Biology
Volume6
Issue number10
Early online date19 Jul 2017
DOIs
DateAccepted/In press - 19 Jul 2017
DateE-pub ahead of print - 19 Jul 2017
DatePublished (current) - 20 Oct 2017

Abstract

In many biotechnological applications, it is useful for gene expression to be regulated by multiple signals, as this allows the programming of complex behavior. Here we implement, in Escherichia coli, a system that compares the concentration of two signal molecules, and tunes GFP expression proportionally to their relative abundance. The computation is performed via molecular titration between an orthogonal σ factor and its cognate anti-σ factor. We use mathematical modeling and experiments to show that the computation system is predictable and able to adapt GFP expression dynamically to a wide range of combinations of the two signals, and our model qualitatively captures most of these behaviors. We also demonstrate in silico the practical applicability of the system as a reference-comparator, which compares an intrinsic signal (reflecting the state of the system) with an extrinsic signal (reflecting the desired reference state) in a multicellular feedback control strategy.

    Research areas

  • synthetic biology

    Structured keywords

  • Bristol BioDesign Institute
  • BrisSynBio

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  • Full-text PDF (final published version)

    Rights statement: This is the final published version of the article (version of record). It first appeared online via ACS at http://pubs.acs.org/doi/abs/10.1021/acssynbio.7b00109. Please refer to any applicable terms of use of the publisher.

    Final published version, 1 MB, PDF document

    Licence: CC BY

  • Supplementary information PDF

    Rights statement: This is the final published version of the article (version of record). It first appeared online via ACS at http://pubs.acs.org/doi/abs/10.1021/acssynbio.7b00109. Please refer to any applicable terms of use of the publisher.

    Final published version, 585 KB, PDF document

    Licence: CC BY

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