Think Tank 5

Time Dependence of Signalling Networks

Description:
General question: What can we learn about network architecture by studying time series of data? More specific question: How can we use this knowledge for the treatment of cancer? The time response of a network after a perturbation depends on its architecture. For signal transduction networks often the sample concentration of phosphorylated proteins is measured over time using (semi-) quantitative western blotting, e.g. after binding of a ligand to its plasma membrane receptor. Emergent properties like robustness, amplification, noise suppression and decisions for apoptosis, senescence, differentiation, etc. can eventually be deduced by mathematical modelling. Abnormalities in cellular signalling networks can disturb the balance between cell survival and cell death, resulting in cancer. Recently “addiction to an oncogene” has been recognized as a feature of some cancers becoming addicted to survival signalling by an overactive oncogene. Inhibition of the corresponding protein (often a kinase) activity or another node directly connected to that protein can lead to a dramatic anti-cancer response and lead to increased survival of the patient. It has been found that an oncogene can result in two opposing signals representing life and death of the cell. The life/death balance can vary over time after a perturbation. The study of the dynamics of this balance and the underlying biochemical reaction kinetics is extremely interesting with regard to translation to timing of perturbations by drugs during chemotherapy.

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