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------------------------------------------------------------------------------ Announcement: Joined SysBio Seminar & SFB Kolloquium ------------------------------------------------------------------------------ Topic -------- A Combined Approach of Single Cell Imaging and Computational Modelling identifies Key Players of Apoptotic Signalling Who ------- Dr. rer. nat. Markus Rehm, Lecturer in Physiology and Biophysics, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland When --------- September 29, 17:15 pm Where ---------- Allmandring 31, 0.106 Abstract ------------ Apoptosis, or programmed cell death, removes superfluous or damaged cells from the body of multi cellular organisms. Enhanced or repressed apoptosis has been shown to contribute to developmental defects, autoimmune diseases, cancer, and neurodegenerative disorders. Intracellular apoptotic signalling is accompanied by the release of mitochondrial proteins into the cytosol, mitochondrial depolarization, and subsequent activation of proteases of the effector caspase family. We established multi-parameter imaging routines to analyse these signalling events spatiotemporally in single living cells using epifluorescence and confocal microscopy. The processes taking place between the initiation of the signalling network and the final effector caspase activation are complex. As naturally experimental set ups are confined to monitor only a limited number of parameters per experiment, quantitatively and temporally little is known about the interactions of the many other proteins within the apoptotic signalling network under physiological conditions. We therefore combined our live cell microscopy experiments with a comprehensive computer model based on the biochemical properties of the proteins involved. With this systems biology approach of live cell imaging and mathematical modelling we were able to characterize the temporal profiles of a multitude of different protein fractions and identified XIAP (X-linked inhibitor of apoptosis protein) as a possible key regulatory protein in the signalling network. Model-generated hypotheses on the progression of apoptotic signalling upon overexpressing XIAP were subsequently tested by live cell microscopy. We indeed identified a sharp XIAP dependent threshold deciding on the efficient activation of effector caspases at an intracellular concentration range closely resembling the computer model prediction. |
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ILS Universität Magdeburg University of Liège driven by sysbio |