Towards Real-Time Control of Gene Expression at the Single Cell Level: A Stochastic Control Approach

  • Lakshmeesh R. M. Maruthi
  • Ilya Tkachev
  • Alfonso Carta
  • Eugenio Cinquemani
  • Pascal Hersen
  • Gregory Batt
  • Alessandro Abate
Conference paper

DOI: 10.1007/978-3-319-12982-2_12

Part of the Lecture Notes in Computer Science book series (LNCS, volume 8859)
Cite this paper as:
Maruthi L.R.M. et al. (2014) Towards Real-Time Control of Gene Expression at the Single Cell Level: A Stochastic Control Approach. In: Mendes P., Dada J.O., Smallbone K. (eds) Computational Methods in Systems Biology. CMSB 2014. Lecture Notes in Computer Science, vol 8859. Springer, Cham

Abstract

Recent works have demonstrated the experimental feasibility of real-time gene expression control based on deterministic controllers. By taking control of the level of intracellular proteins, one can probe single-cell dynamics with unprecedented flexibility. However, single-cell dynamics are stochastic in nature, and a control framework explicitly accounting for this variability is presently lacking. Here we devise a stochastic control framework, based on Model Predictive Control, which fills this gap. Based on a stochastic modelling of the gene response dynamics, our approach combines a full state-feedback receding-horizon controller with a real-time estimation method that compensates for unobserved state variables. Using previously developed models of osmostress-inducible gene expression in yeast, we show in silico that our stochastic control approach outperforms deterministic control design in the regulation of single cells. The present new contribution leads to envision the application of the proposed framework to wetlab experiments on yeast.

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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Lakshmeesh R. M. Maruthi
    • 1
  • Ilya Tkachev
    • 1
  • Alfonso Carta
    • 2
  • Eugenio Cinquemani
    • 3
  • Pascal Hersen
    • 4
  • Gregory Batt
    • 5
  • Alessandro Abate
    • 1
    • 6
  1. 1.Delft Center for Systems and ControlTU DelftThe Netherlands
  2. 2.INRIA Sophia-AntipolisMéditerranéeFrance
  3. 3.INRIA GrenobleRhône-AlpesFrance
  4. 4.UMR 7057Laboratoire Matière et Systèmes ComplexesParisFrance
  5. 5.INRIA Paris-RocquencourtFrance
  6. 6.Department of Computer ScienceUniversity of OxfordUK

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