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In Vivo Real-Time Control of Gene Expression: A Comparative Analysis of Feedback Control Strategies in Yeast

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)154-162
Number of pages9
JournalACS Synthetic Biology
Issue number2
DatePublished - 2015


Real-time automatic regulation of gene expression is a key technology for synthetic biology enabling, for example, synthetic circuit’s components to operate in an optimal range. Computer-guided control of gene expression from a variety of inducible promoters has been only recently successfully demonstrated. Here we compared, in silico and in vivo, three different control algorithms: the Proportional Integral (PI) and Model Predictive Control (MPC) controllers, which have already been used to control gene expression, and the Zero Average Dynamics (ZAD), a control technique used to regulate electrical power systems. We chose as an experimental testbed the most commonly used inducible promoter in yeast: the galactose-responsive GAL1 promoter. We set two control tasks: either force cells to express a desired constant fluorescence level of a reporter protein downstream of the GAL1 promoter (set-point) or a time-varying fluorescence (tracking). Using a microfluidics-based experimental platform, in which either glucose or galactose can be provided to the cells, we demonstrated that both the MPC and ZAD control strategies can successfully regulate gene expression from the GAL1 promoter in living cells for thousands of minutes. The MPC controller can track fast reference signals better than ZAD but with a higher actuation effort due to the large number of input switches it requires. Conversely, the PI controller’s performance is comparable to that achieved by the MPC and the ZAD controllers only for the set-point regulation.

    Structured keywords

  • Bristol BioDesign Institute

    Research areas

  • synthetic biology, control engineering, microfluidics, gene expression, yeast

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  • Gianfranco Fiore - In-vivo real-time control of gene expression

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via American Chemical Society at Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 626 KB, PDF document


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