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In silico feedback for in vivo regulation of a gene expression circuit

Nature Biotechnology volume 29, pages 1114–1116 (2011)Cite this article

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Abstract

We show that difficulties in regulating cellular behavior with synthetic biological circuits may be circumvented using in silico feedback control. By tracking a circuit's output in Saccharomyces cerevisiae in real time, we precisely control its behavior using an in silico feedback algorithm to compute regulatory inputs implemented through a genetically encoded light-responsive module. Moving control functions outside the cell should enable more sophisticated manipulation of cellular processes whenever real-time measurements of cellular variables are possible.

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Figure 1: Characterization of the light-switched system.
Figure 2: In silico feedback achieves robust regulation of gene expression fold change.

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Acknowledgements

We would like to thank P. Quail (UC, Berkeley) for the generous gift of the PIF3 construct and W. Lim (UCSF) and J. Stelling (ETH, Zurich) for providing PCB. The work was supported by National Science Foundation grant CCF-0943385 (H.E.-S.), ECCS-0835847 (M.K.), and MoVeS FP7-ICT-2009-257005 (J.L.).

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Author notes

  1. Andreas Milias-Argeitis, Sean Summers and Jacob Stewart-Ornstein: These authors contributed equally to this work.

  2. lygeros@control.ee.ethz.ch

Authors and Affiliations

  1. Department of Electrical Engineering, ETH Zurich, Automatic Control Laboratory, Zurich, Switzerland

    Andreas Milias-Argeitis, Sean Summers & John Lygeros

  2. Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, USA

    Jacob Stewart-Ornstein, Ignacio Zuleta, David Pincus & Hana El-Samad

  3. Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland

    Mustafa Khammash

Authors
  1. Andreas Milias-Argeitis
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  2. Sean Summers
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  3. Jacob Stewart-Ornstein
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  4. Ignacio Zuleta
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  6. Hana El-Samad
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  7. Mustafa Khammash
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  8. John Lygeros
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Corresponding authors

Correspondence to Hana El-Samad or Mustafa Khammash.

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The authors declare no competing financial interests.

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Supplementary Methods and Supplementary Figures 1–4 (PDF 651 kb)

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Milias-Argeitis, A., Summers, S., Stewart-Ornstein, J. et al. In silico feedback for in vivo regulation of a gene expression circuit. Nat Biotechnol 29, 1114–1116 (2011). https://doi.org/10.1038/nbt.2018

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  • DOI: https://doi.org/10.1038/nbt.2018

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