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

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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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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