CANCER

Possible Submerge Research Projects – Ordinary, Delay, or Age-structured Differential Equations The Bcl Family of Proteins and Cell Death

It is widely reported that the outcome of death signals that are regulated by the BCL-2 family depends upon a complex three-way ratio of the multi-domain anti-apoptotic, multi-domain pro-apoptotic, and BH3-only members.  Specifically, Bax and Bak (multi-domain pro-apoptotic members) represent the central core of the proapoptotic Bcl-2 death machinery that is held in check by the pro-survival members Bcl-2 and Bcl-XL. However, members of the BH3-only subfamily are required for the activation of proapoptotic Bax/Bak function [Bouillet, 2002].  Further, there is evidence that BH3-only members function upstream of Bax and Bak [Lindsten, 2000; Wei, 2001 and that the killing effect of BH3-only members depends on Bax/Bak, see figure below adapted from Shore, G. C. et al. Hematology 2005:226-230. The goal of this project is to develop a model of the cell death cascade and link it to a population model of cell response to external death signals.

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