Dynamics of Cell Fate Decision Mediated by the Interplay of Autophagy and Apoptosis in Cancer Cells: Mathematical Modeling and Experimental Observatio

ISBN-13: 9783319365121 / Angielski / Miękka / 2016 / 79 str.

Iman Tavassoly

Opis

This interdisciplinary thesis introduces a systems biology approach to study the cell fate decision mediated by autophagy. A mathematical model of interaction between Autophagy and Apoptosis in mammalian cells is proposed. In this dynamic model autophagy acts as a gradual response to stress (Rheostat) that delays the initiation of bistable switch of apoptosis to give the cells an opportunity to survive. The author shows that his dynamical model is consistent with existing quantitative measurements of time courses of autophagic responses to cisplatin treatment. To understand the function of this response in cancer cells, he has provided a systems biology experimental framework to study quantitative and dynamical aspects of autophagy in single cancer cells using live-cell imaging and quantitative fluorescence microscopy. This framework can provide new insights on function of autophagic response in cancer cells.

Spis treści

1 Introduction 1.1 Cell Death Modalities in Cancer 1.2 Autophagy Pathway 1.3 Selective Autophagy 1.4 Autophagy and Pathogenesis of Diseases 1.5 Autophagy and Metabolism in Cancer 1.6 Signaling Pathway Controlling Interplay of Autophagy and Apoptosis 1.6.1 Calcium Signaling from ER to Mitochondrion 1.6.2 DAPK Fine Tunes the Autophagic Response Bibliography 2 Mathematical Modeling of the Interplay of Autophagy and Apoptosis 2.1 Systems Biology of Cell Death Pathways 2.2 Dynamic Modeling of the Interplay of Autophagy and Apoptosis 2.2.1 Mathematical Formalism 2.2.2 Results 2.2.3 Future Directions 3 An Experimental Framework to Study the Dynamics of Autophagic Response 3.1 Methods to Detect and Measure Autophagy 3.2 Quantitative Parameters of Autophagic Response 3.3 Experimental Observations in Human H4 Neuroglioma Cells 3.4 Experimental Observations in Breast Cancer Cells 3.4.1 Basal Autophagy in Breast Cancer Cells 3.4.2 Autophagy, Cell Growth and Cell Cycle 3.4.3 Serum Starvation-Induced Autophagy in Breast Cancer Cells 3.5 Current Realities and Future Directions Bibliography 4 Conclusions Bibliography 5 Source Code

O autorze

Iman Tavassoly (MD, PhD) is a physician-scientist working at Icahn School of Medicine at Mount Sinai and Systems Biology Center New York. His research interests include systems biology of complex diseases and cancer biology. He graduated from medical school in 2007 and received his PhD in Genetics, Bioinformatics and Computational Biology at Virginia Tech where he was awarded as the outstanding interdisciplinary program doctoral student.