Biological Information Technology Systems - BITS: Modeling and Analysis of Biological and Information Networks

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

EIA-0130797 -Harvey Rubin-University of Pennsylvania-Modeling and Analysis of Biological and Information Networks The overall goals of our research are to: 1) create enabling technologies and experimental systems that are necessary to understand and predict the integrated functions of two bacterial sensing and regulatory networks--porim osmo-regulation in E.coli and oxygen sensing regulation of DNA synthesis in Mycobacterium tuberculosis; 2) model and abstract principles of organization, design control and coordination of biological systems. We believe that a better understanding of networked, hybrid models in biology will provide deeper insights into networked, embedded systems. No systematic approach to designing and developing such hybrid systems exists today. Our research on the porin osmo-regulatory system in E. coli will investigate crosstalk between the porin osmo-regulatory system and other signaling systems. We suggest that the ability of the sensing element of the system, EnvZ, to act as both a kinase and phosphatase is crucial for the control of information flow and to minimize crosstalk. We will extend our models in a related series of experiments on the PhoQ/PhoP two component systems, which responds to changes in the extracellular magnesium concentration. Since the levels of the histidine kinase PhoQ and response regulator PhoP are modulated by the concentration of phosphorylated PhoP, we will be able to establish the effect of this feedback and its influence on robustness of the overall system behavior.