By Iman Tavassoly
This interdisciplinary thesis introduces a platforms biology method of examine the phone destiny choice mediated by means of autophagy. A mathematical version of interplay among Autophagy and Apoptosis in mammalian cells is proposed. during this dynamic version autophagy acts as a gentle reaction to emphasize (Rheostat) that delays the initiation of bistable swap of apoptosis to offer the cells a chance to outlive. the writer exhibits that his dynamical version is in line with current quantitative measurements of time classes of autophagic responses to cisplatin remedy. to appreciate the functionality of this reaction in melanoma cells, he has supplied a platforms biology experimental framework to check quantitative and dynamical features of autophagy in unmarried melanoma cells utilizing live-cell imaging and quantitative fluorescence microscopy. This framework grants new insights on functionality of autophagic reaction in melanoma cells.
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Extra resources for Dynamics of Cell Fate Decision Mediated by the Interplay of Autophagy and Apoptosis in Cancer Cells: Mathematical Modeling and Experimental Observations
WDAPK_0 C wDAPK_S S / which varies between 0 (no activation) and 1 (full activation). Roughly speaking, the steepness of the sigmoid function is governed by D , and DAPK is half-activated when S D wDAPK_0 =wDAPK_S . The rate at which DAPK moves towards its steadystate value is controlled by the rate constant D . H. ), and Xi is the concentration of the active form of species i. i is a rate constant determining how fast Xi approaches its steady-state value . The function H. i Wi / is sigmoidally shaped, varying from 0 for Wi << 1= i to 1 for Wi >> 1= i .
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Physiology 23(5), 248–262 (2008) 147. : Eating the endoplasmic reticulum: quality control by autophagy. Trends Cell Biol. 17(6), 279–285 (2007) 148. : Calpain-mediated cleavage of atg5 switches autophagy to apoptosis. Nat. Cell Biol. 8(10), 1124–1132 (2006) 149. : Phosphorylation of beclin 1 by dap-kinase promotes autophagy by weakening its interactions with BCL-2 and BCL-XL. Autophagy 5(5), 720–722 (2009) 150. : DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from BCL-XL and induction of autophagy.
Dynamics of Cell Fate Decision Mediated by the Interplay of Autophagy and Apoptosis in Cancer Cells: Mathematical Modeling and Experimental Observations by Iman Tavassoly