Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Session III Abstracts

Modeling and Dynamic Analysis of Feedback Loops of the Insulin and Angiotensin II Signalling Systems

Yaman Arkun 1 , Deniz Cizmeci 2 . 1 Koc University, Istanbul, Turkey, 2 University of Exeter, Exeter, United Kingdom This work applies the tools of systems theory to analyze the structure and the dynamics of the complex cellular networks associated with diabetes and hypertension. The primary research focus is the interaction between Angiotensin II (Ang II) and Insulin AKT signalling pathways. We provide a better understanding of design and operating principles of processes such as glucose uptake, cell proliferation, and blood pressure control by developing mathematical models of interactions at the system level. The overall model is a dynamic nonlinear model that includes mass-action kinetics and conservation laws. System behavior is analyzed within the context of signalling pathways and feedback regulation. We show that complex signalling pathways that govern the cross-talk between hypertension and diabetes are regulated by a nested set of feedback loops that are organized in hierarchical fashion. Using the dynamic models we develop, we simulate different scenarios to elucidate the functions of these feedback structures. While doing so, dominant steady-state and dynamic characteristics that determine the normal and diseased states are revealed. In particular parametric sensitivity and bistability of these feedback loops are shown to affect the regulatory mechanisms such as glucose uptake and vasodilation- vasoconstriction balance.

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