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

Fabio Annunziata, Antoni Matyjaszkiewicz, Gianfranco Fiore, Claire Grierson, Mario Di Bernardo, Lucia Marucci, Nigel Savery

Research output: Contribution to journalLetter (Academic Journal)peer-review

34 Citations (Scopus)
627 Downloads (Pure)


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.
Original languageEnglish
Pages (from-to)1816-1824
Number of pages9
JournalACS Synthetic Biology
Issue number10
Early online date19 Jul 2017
Publication statusPublished - 20 Oct 2017

Structured keywords

  • Bristol BioDesign Institute
  • BrisSynBio
  • Engineering Mathematics Research Group


  • synthetic biology


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