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Special Semester on Quantitative Biology analyzed by Mathematical Methods
Linz, October 1, 2007 - January 27, 2008
Perturbing and Analyzing the Dynamics of Apoptosis in Single Cells

Workshop on Systems Biology, Tue, 06 Nov, 2007

Speaker: Bree Aldridge

Abstract

Receptor-mediated cell death – apoptosis – is typically characterized by activation of effector proteases, called caspases, which make a binary die-or-survive decision. A key feature of apoptosis is the rapid “all-or-nothing” activation of these caspases. Without this, cells that develop genomic instability from the partial caspase activation may survive, potentially leading to oncogenesis. To quantitatively understand the breakdown of this necessary switch-like mechanism, we use a combined computational and experimental approach. Computationally, we use direct Lyapunov exponents to quantitatively analyze transient signals in our physicochemical model. This analysis allows us to quantitatively separate the signaling- (phase-) space into regions destined for cell survival or death, in a system where steady-state analysis is inadequate. Experimentally, we use live-cell imaging with fluorescence-based reporters to quantitatively monitor the activities of different components of the apoptosis network.

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