Summary: Hybrid Modeling and Simulation of Biomolecular Networks
Rajeev Alur, Calin Belta, Franjo IvanŸci'c, Vijay Kumar, Max Mintz, George Pappas, Harvey Rubin, and
Jonathan Schug
University of Pennsylvania
Abstract. In a biological cell, cellular functions and the genetic regulatory apparatus are imple­
mented and controlled by a network of chemical reactions in which regulatory proteins can control
genes that produce other regulators, which in turn control other genes. Further, the feedback path­
ways appear to incorporate switches that result in changes in the dynamic behavior of the cell. This
paper describes a hybrid systems approach to modeling the intra­cellular network using continuous
differential equations to model the feedback mechanisms and mode­switching to describe the changes
in the underlying dynamics. We use two case studies to illustrate a modular approach to modeling
such networks and describe the architectural and behavioral hierarchy in the underlying models.
We describe these models using Charon [2], a language that allows formal description of hybrid
systems. We provide preliminary simulation results that demonstrate how our approach can help
biologists in their analysis of noisy genetic circuits. Finally we describe our agenda for future work
that includes the development of models and simulation for stochastic hybrid systems. We believe
that an understanding of the redundant design for robust regulation of noisy biological processes
may help engineers in designing, organizing and programming distributed embedded systems.
1 Introduction
In order to survive, organisms continuously monitor their surroundings and, if necessary, adjust traffic

Source: Alur, Rajeev - Department of Computer and Information Science, University of Pennsylvania

Collections: Computer Technologies and Information Sciences