QSB: Reconstruction and Simulation of Genome-Scale Regulatory Networks

University Of California-San Diego, La Jolla CA

Investigators

Abstract

A systems point of view of cellular functions has emerged as a result of a broadening spectrum of high-throughput experimental technologies. The systems biology process is commonly viewed as being comprised of four major steps: 1) enumeration of biological components, 2) network reconstruction, 3) mathematical modeling and simulation of network properties and 4) comparison of computed and experimentally observed behavior and systematic reconciliation of discrepancies. For microbial metabolism these four steps have been completed for several organisms demonstrating that the process is feasible. While building genome-scale representations of metabolism in this way may be considered well established, the same is not true for regulatory networks. This project is aimed at establishing an integrated framework for building, simulating, and expanding models of transcriptional regulatory networks, and thus generating the capability to incorporate them into genome-scale models of metabolism in microbial organisms. Specifically, the Principal Investigator (PI) will pursue three goals: 1) to develop and apply methods for refining and expanding known regulatory networks (built using information from literature and curated databases) by using high-throughput gene expression and location analysis data; 2) to develop and evaluate mathematical modeling approaches for simulation of reconstructed regulatory networks integrated with constraints-based metabolic models; and 3) to develop and apply methods for iterative model-building in order to formulate a procedure to systematically expand the scope of regulatory and metabolic network models. The third goal is the most innovative and involves the highest risk.