Brief Communication | Published:

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

Nature Biotechnology volume 29, pages 11141116 (2011) | Download Citation

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Nat. Rev. Mol. Cell Biol. 11, 393–403 (2010).

  2. 2.

    , , & Mol. Syst. Biol. 2 2006.0028 (2006).

  3. 3.

    & Nat. Rev. Genet. 6, 533–543 (2005).

  4. 4.

    & Nat. Rev. Genet. 11, 367–379 (2010).

  5. 5.

    & Nat. Rev. Mol. Cell Biol. 10, 410–422 (2009).

  6. 6.

    & J. Cell Biol. 187, 589–596 (2009).

  7. 7.

    , , & Nature 461, 997–1001 (2009).

  8. 8.

    & Nat. Methods 5, 303–305 (2008).

  9. 9.

    , , & Proc. Natl. Acad. Sci. USA 105, 12797–12802 (2008).

  10. 10.

    , , & Nat. Biotechnol. 20, 1041–1044 (2002).

  11. 11.

    J. Basic Eng. 82, 35–45 (1960).

  12. 12.

    Comput. Chem. Eng. 23, 667–682 (1999).

  13. 13.

    et al. J. Biol. Eng. 3, 15 (2009).

Download references

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.).

Author information

Author notes

    • Andreas Milias-Argeitis
    • , Sean Summers
    •  & Jacob Stewart-Ornstein

    These authors contributed equally to this work.

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. Search for Andreas Milias-Argeitis in:

  2. Search for Sean Summers in:

  3. Search for Jacob Stewart-Ornstein in:

  4. Search for Ignacio Zuleta in:

  5. Search for David Pincus in:

  6. Search for Hana El-Samad in:

  7. Search for Mustafa Khammash in:

  8. Search for John Lygeros in:

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Hana El-Samad or Mustafa Khammash.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Methods and Supplementary Figures 1–4

About this article

Publication history

Received

Accepted

Published

DOI

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

Further reading