Modeling The Unfolded Protein Response And Its Connection To Cellular Stress
The Endoplasmic Reticulum (ER) plays a pivotal role in cellular functioning. Proteins undergo modifications in the ER. The cell monitors protein folding and has a quality control. The incorrectly folded proteins are tagged for degradation or sent back to the refolding cycle. Upon accumulation of incorrectly folded proteins in the cell, due to any alterations in the cellular homeostasis, cellular stress is created. This leads to a cascade of events, termed the Unfolded Protein Response (UPR). Cellular stresses range from hypoxia, nutrient deprivation to external stimulus such as heat or radiation. It is vital to understand the complexities involved in this system, to predict the role of UPR in cancer, diabetes and other diseases associated with misfolded proteins. In the current study, we have created an initial model of the UPR. This model is based on mass action kinetics. We solve this model deterministically, to look at the concentration profiles of the proteins and protein complexes, upon UPR induction. This kind of study, along with the mathematical and statistical tools developed in the Varner lab provide tools to identify fragile elements of the UPR network. These fragile components of the system become targets for intervention by drugs and inform the development of experiments to discover new pharmaceutical treatments.
dissertation or thesis