Berlin 2005 – wissenschaftliches Programm
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AKB: Biologische Physik
AKB 20: Systems Biology and Bioinformatics
AKB 20.2: Hauptvortrag
Freitag, 4. März 2005, 14:30–15:00, TU H2013
Systems Biology of the JAK-STAT signalling pathway — •Jens Timmer1 and Ursula Klingmüller2 — 1Centre for Data Analysis and Modelling, University of Freiburg, Eckerstr. 1, 79104 Freiburg — 2German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg
Considerable progress has been made in identifying the molecular composition of cellular signalling networks. However, to reveal the systems’ properties, quantitative models based on experimental data have to be developed. To demonstrate this Systems Biology approach, we investigate the core module of the JAK-STAT pathway of the Epo-receptor. Based on time resolved quantitative measurement of the involved proteins, we estimate the parameters in differential equations describing the pathway. The results show that the so far believed assumption of a feed-forward cascade to describe the pathway does not hold. A generalization of the model that includes nucleocytoplasmatic cycling is suggested and validated by successfully predicting the outcome of a new experiment. From this model, we infer the time courses of the unobserved STAT populations and show that, on a systems level, fast nucleocytoplasmatic cycling of STAT serves as a remote sensor to closely couple gene activation to receptor activity.