Underlying the biology of individual living cells is a remarkably intricate biochemical machinery that permits the cell to perform complex metabolic functions, to respond precisely to external signals, and to replicate itself faithfully even when subjected to a wildly fluctuating environment. This machinery comprises networks of interconnected biochemical reaction modules, each involving multiple chemical reactions and a variety of distinct molecular species. Nature appears to employ certain unifying design principles life-strategies that evolved over hundreds of millions of years to tailor the structures of reaction network modules to the cellular tasks they execute. The goal of this project is to develop a comprehensive theory of the relationship between reaction network structure and reaction network behavior, and thus increase the understanding of how cells function and respond robustly to environmental changes. The research requires expertise in biology, mathematics, and chemical engineering and will be carried out by an inter-disciplinary team based at Ohio State University collaborating with a pioneering group at the Weizmann Institute of Science in Rehovet, Israel.
Broader Impacts: Fundamental theoretical understanding of structure-function relationships in biochemical networks will have a broad impact on biological science, with applications in the analysis of specific systems and the design of new ones. Just as electrical circuit theory was key to the development of the electronics industry, an incisive theory of biochemical circuitry is expected to be fundamental for development of the emerging discipline of synthetic biology, which seeks to fashion new and useful devices from biological components. The project will support the education of a graduate student. A widely disseminated computer program developed by the PI to model biochemical reaction networks will be updated to reflect new theory and computing capabilities. It will be disseminated to practitioners in the field and used as a basis for innovative outreach to engage high school and undergraduate students in synthetic biology and molecular bioengineering.