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A Detailed Kinetic Model for a Bistable Genetic Network

Aditya Pratap Singh, Department of Chemical Engineering, University of Delaware, Allan P. Colburn Lab, 150 Academy Street, Newark, DE 19716 and Jeremy S. Edwards, Chemical and Nuclear Engineering, University of New Mexico.

The field of synthetic biology has emerged in the post-genome era. Synthetic biology focuses on the design, analysis and construction of artificial biological networks, and is thus analogous to other engineering fields; where the design of networks and systems is based on a detailed understanding of the individual components that are modeled using systems approaches and the final design is based on the simulation results. In this manuscript, we describe a detailed mechanistic kinetic model of a double negative feedback system that can be used in the design of bistable biological networks. Using the model, we identified the kinetic parameters responsible for controlling the reversibility of the bistable system. We investigate the reversal of epigenetic memory for bistable genetic networks. An explanation of reversibility in terms of a stochastic formalism is also provided. We also defined the dimensionless parameter that controls the maximum number of TetR repressor molecules. Analysis of such a model will help understand biological control systems and can be used in the design of the genetic networks by providing a deeper insight into the mechanisms giving rise to the emergent properties of biological networks.