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SYSTEMS BIOLOGY
Cell and Tissue ModelingSystems Biology:The last decade has seen quantum leaps in the field of systems biology with far-reaching applications in various fields. We focus on the developing an in silico model of blood flow in artery whose flow and pressure are regulated by NO signaling pathways. Starting at the shear stress and/or ligand induced effectors at the upstream to endothelial cell, the eNOS activation leading to NO release and smooth muscle relaxation are being reconstructed. Kinetic simulation of biochemical network: Endothelial cells in response to a particular stimulus undergo membrane reorganization and cytoskeletal remodeling. Endothelial Nitric Oxide Synthase (eNOS) is constitutively expressed in the endothelial cells and participates in various signaling cascades. Signaling pathways that regulate eNOS activity include phosphoinositide 3-kinase/Akt, Cyclic nucleotide dependent kinase, PKC and ERK. Activation of eNOS leads to the production of nitric oxide, which mediates a large number of physiological and pathophysiological processes. We focuses on spatio-temporal systemics of endothelial cell signal-transduction mechanisms. Specifically, we study eNOS activating pathways in silico. Incorporating into the computational model - cellular network integration, concentrating on the major components such as small GTPases (Rac, Rho and Cdc42) and downstream effectors involved in cytoskeletal and membrane remodeling, we plan to develop a generic model of eNOS activation process for variety of endothelial systems. In silico modeling of the eNOS activation pathway is performed using the GENESIS Simulator Simulations are constructed from modules that receive input (rate constants and other relevant kinetic data), perform calculations on them and generate the required output.
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