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In Silico Control of Biomolecular Processes

  • Jannis Uhlendorf
  • Agnès Miermont
  • Thierry Delaveau
  • Gilles Charvin
  • François Fages
  • Samuel Bottani
  • Pascal HersenEmail author
  • Gregory BattEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1244)

Abstract

By implementing an external feedback loop one can tightly control the expression of a gene over many cell generations with quantitative accuracy. Controlling precisely the level of a protein of interest will be useful to probe quantitatively the dynamical properties of cellular processes and to drive complex, synthetically-engineered networks. In this chapter we describe a platform for real-time closed-loop control of gene expression in yeast that integrates microscopy for monitoring gene expression at the cell level, microfluidics to manipulate the cells environment, and original software for automated imaging, quantification, and model predictive control. By using an endogenous osmo-stress responsive promoter and playing with the osmolarity of the cells environment, we demonstrate that long-term control can indeed be achieved for both time-constant and time-varying target profiles, at the population level, and even at the single-cell level.

Key words

Model predictive control Gene expression High-osmolarity glycerol (HOG) pathway Computational biology Quantitative systems and synthetic biology 

Notes

Acknowledgments

We acknowledge the support of the Agence Nationale de la Recherche (under the references DiSiP-ANR-07-JCJC-0001 and ICEBERG-ANR-10-BINF-06-01), of the Région Ile de France (C’Nano-ModEnv), of the Action d’Envergure ColAge from INRIA/INSERM (Institut Nationale de la Santé et de la Recherche Médicale), of the MechanoBiology Institute, and of the Laboratoire International Associé CAFS (Cell Adhesion France-Singapour).

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Jannis Uhlendorf
    • 1
    • 2
  • Agnès Miermont
    • 2
  • Thierry Delaveau
    • 3
  • Gilles Charvin
    • 4
  • François Fages
    • 1
  • Samuel Bottani
    • 2
  • Pascal Hersen
    • 2
    • 5
    • 6
    Email author
  • Gregory Batt
    • 1
    Email author
  1. 1.INRIA Paris-RocquencourtLe ChesnayFrance
  2. 2.Laboratoire Matière et Systèmes Complexes, UMR 7057 CNRSUniversité Paris DiderotParisFrance
  3. 3.Laboratoire de Génomique des Microorganismes, UMR 7238 CNRSUniversité Pierre et Marie CurieParisFrance
  4. 4.Institut de Biologie Moléculaire et CellulaireIllkirchFrance
  5. 5.The Mechanobiology InstituteNational University of SingaporeSingaporeSingapore
  6. 6.Laboratoire Matière et Systèmes ComplexesUniversité Paris Diderot-Paris 7Paris, Cedex 13France

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