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

Autophagy is a conserved biological stress response in mammalian cells that is responsible for clearing damaged proteins and organelles from the cytoplasm and recycling their contents via the lysosomal pathway. In cases where the stress is not too severe, autophagy acts as a survival mechanism. In cases of severe stress, it may lead to programmed cell death. Autophagy is abnormally regulated in a wide-range of diseases, including cancer. To integrate the existing knowledge about this decision process into a rigorous, analytical framework, we built a mathematical model of cell fate decision mediated by autophagy. The model treats autophagy as a gradual response to stress that delays the initiation of apoptosis to give the cell an opportunity to survive. We show that our 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 we have provided a systems biology experimental framework to study dynamical aspects of autophagy in single cancer cells using live-cell imaging and quantitative uorescence microscopy. This framework can provide new insights on function of autophagic response in cancer cells.

Name thesis:degree_name

Ph. D.

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Genetics, Bioinformatics, and Computational Biology

Department dc:contributor.department

Animal and Poultry Sciences

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2013

Author dc:creator

• Tavassoly, Iman

Chair dc:contributor.committeechair

• Tyson, John J.

Committee members dc:contributor.committeemember

• Clarke, Robert
• Baumann, William T.
• Li, Liwu
• Finkielstein, Carla V.

• Apoptosis
• Autophagy
• Cancer
• Cell Death
• Dynamic Modeling
• Live Cell Imaging
• Quantitative Fluorescence Microscopy
• Single-Cell

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Dc Identifier Other

vt_gsexam:1530

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/79557