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Interaction between Experiment, Modeling and Simulation of Spatial Aspects in the JAK2/STAT5 Signaling Pathway

Friedmann, Elfriede and Pfeifer, Andrea C. and Neumann, Rebecca and Klingmüller, Ursula and Rannacher, Rolf

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Abstract

Fundamental progress in systems biology can only be achieved if experimentalists and theoreticians closely collaborate. Mathematical models cannot be formulated precisely without deep knowledge of the experiments while complex biological systems can often not be understood fully without mathematical interpretation of the dynamic processes involved. In this article, we describe how these two approaches can be combined to gain new insights on one of the most extensively studied signal transduction pathways, the Janus kinase (JAK)/ signal transducer and activator of transcription (STAT) pathway. We focus on the parameters of a model describing how STAT proteins are transported from the membrane to the nucleus where STATs regulate gene expression. We discuss which parameters can be measured experimentally in different cell types and how the unknown parameters are estimated, what the limits of these techniques and how accurate the determinations are.

Translation of abstract (English)

Fundamental progress in systems biology can only be achieved if experimentalists and theoreticians closely collaborate. Mathematical models cannot be formulated precisely without deep knowledge of the experiments while complex biological systems can often not be understood fully without mathematical interpretation of the dynamic processes involved. In this article, we describe how these two approaches can be combined to gain new insights on one of the most extensively studied signal transduction pathways, the Janus kinase (JAK)/ signal transducer and activator of transcription (STAT) pathway. We focus on the parameters of a model describing how STAT proteins are transported from the membrane to the nucleus where STATs regulate gene expression. We discuss which parameters can be measured experimentally in different cell types and how the unknown parameters are estimated, what the limits of these techniques and how accurate the determinations are.

Item Type: Preprint
Date Deposited: 21. Nov 2011 12:04
Date: 2010
Faculties / Institutes: The Faculty of Mathematics and Computer Science > Department of Applied Mathematics
Service facilities > Uni-externe Einrichtungen
Subjects: 510 Mathematics
Controlled Keywords: Helmholtz Alliance on Systems Biology (SBCancer, Submodule V.7), FORSYS-ViroQuant (#0313923)
Uncontrolled Keywords: JAK2/STAT5 Signalweg, Reaktions-Diffusionsgleichungen, ParameterschätzungJAK2/STAT5 Signaling Pathway, Reaction Diffusion Equations, Parameter Estimation
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