MATHEMATICAL MODELING OF CASPASE

Abstract

Cells are programmed to stay alive, develop and die through a series of complex and tightly regulated system, particularly, apoptosis-indispensable in controlling many aspects of normal physiology such as maintaining homeostasis, embryonic development and immunity.

Caspases (Cysteine- dependent ASPartyl-specific proteASES) are the core elements responsible for biochemical and morphological changes in cell suicide. They are synthesized as inactive zymogens (procaspases) in cells [4, 11] and activated by extrinsic and intrinsic apoptotic signaling pathways proteolytically.

It is crucial to understand the molecular mechanisms of apoptosis to identify the main causes of multiple pathologies where cell suicide begins. Dysfunctional apoptotic programs are the contributing factors to various diseases ranging from neurodegenerative disorders to cancer.

The objective of this project is to build a mathematical based on newly emerging biological information to explain the main elements of receptor-mediated and stress-induced apoptotic signaling pathways on caspase activations. Matlab and Simulink are used to construct ordinary differential equations (ODEs) and to simulate the respective signaling pathways. Simulation results of activated caspases are consistent with experimental findings.

This quantitative mathematical model provides a flexible yet meticulous framework to store, visualize and interact with the current, updated emerging elements. The model will enable biologists to quantitate experimental outcomes and identify points of intervention to test their hypotheses. Together with experimental work, the model can be used for investigating novel therapeutic strategies for aberrations in cell death processes.