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Optimal control of self-organized dynamics in cellular signal transduction

Author

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  • O. Slaby
  • S. Sager
  • O. S. Shaik
  • U. Kummer
  • D. Lebiedz

Abstract

We demonstrate how model-based optimal control can be exploited in biological and biochemical modelling applications in several ways. In the first part, we apply optimal control to a detailed kinetic model of a glycolysis oscillator, which plays a central role in immune cells, in order to analyse potential regulatory mechanisms in the dynamics of associated signalling pathways. We demonstrate that the formulation of inverse problems with the aim to determine specific time-dependent input stimuli can provide important insight into dynamic regulations of self-organized cellular signal transduction. In the second part, we present an optimal control study aimed at target-oriented manipulation of a biological rhythm, an internal clock mechanism related to the circadian oscillator. This oscillator is responsible for the approximate endogenous 24 h (latin: circa dies) day-night rhythm in many organisms. On the basis of a kinetic model for the fruit fly Drosophila, we compute switching light stimuli via mixed-integer optimal control that annihilate the oscillations for a fixed time interval. Insight gained from such model-based specific manipulation may be promising in biomedical applications.

Suggested Citation

  • O. Slaby & S. Sager & O. S. Shaik & U. Kummer & D. Lebiedz, 2007. "Optimal control of self-organized dynamics in cellular signal transduction," Mathematical and Computer Modelling of Dynamical Systems, Taylor & Francis Journals, vol. 13(5), pages 487-502, October.
    • Handle: RePEc:taf:nmcmxx:v:13:y:2007:i:5:p:487-502
    DOI: 10.1080/13873950701243969
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    References listed on IDEAS

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    1. Albert Goldbeter, 2002. "Computational approaches to cellular rhythms," Nature, Nature, vol. 420(6912), pages 238-245, November.
    2. Steven M. Reppert & David R. Weaver, 2002. "Coordination of circadian timing in mammals," Nature, Nature, vol. 418(6901), pages 935-941, August.
    3. Michael J. Berridge, 1997. "The AM and FM of calcium signalling," Nature, Nature, vol. 386(6627), pages 759-760, April.
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    Cited by:

    1. Neda Bagheri & Jörg Stelling & Francis J Doyle III, 2008. "Circadian Phase Resetting via Single and Multiple Control Targets," PLOS Computational Biology, Public Library of Science, vol. 4(7), pages 1-10, July.
    2. Bersani, Alberto Maria & Carlini, Elisabetta & Lanucara, Piero & Rorro, Marco & Ruggiero, Vittorio, 2010. "Application of Optimal Control techniques and Advanced Computing to the study of enzyme kinetics," Mathematics and Computers in Simulation (MATCOM), Elsevier, vol. 81(3), pages 705-716.

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