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Systems biology of apoptosis

  • Martin Bentele
  • Roland Eils
Chapter
Part of the Topics in Current Genetics book series (TCG, volume 13)

Abstract

New approaches are required for the mathematical modelling and system identification of complex signal transduction networks, which are characterized by a large number of unknown parameters and partially poorly understood mechanisms. Here, a new quantitative system identification method is described, which applies the novel concept of ’Sensitivity of Sensitivities’ revealing two important system properties: high robustness and modular structures of the dependency between state variables and parameters. This is the key to reduce the system’s dimensionality and to estimate unknown parameters on the basis of experimental data. The approach is applied to CD95-induced apoptosis, also called programmed cell death. Defects in the regulation of apoptosis result in a number of serious diseases such as cancer. With the estimated parameters, it becomes possible to reproduce the observed system behaviour and to predict important system properties. Thereby, a novel regulatory mechanism was revealed, i.e. a threshold between cell death and cell survival.

Keywords

System Biology Ligand Concentration Death Process Global Parameter Signal Transduction System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Authors and Affiliations

  • Martin Bentele
    • 1
  • Roland Eils
    • 1
  1. 1.Division Theoretical Bioinformatics, German Cancer Research Center (DKFZ), 69120 HeidelbergGermany

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