Design Principles of Biochemical Reaction Networks

智力优势：在单个活细胞的生物学基础上，是一种非常复杂的生化机制，它允许细胞执行复杂的代谢功能，对外部信号做出精确的反应，甚至在受到剧烈波动的环境时也能忠实地复制自己。这种机制包括相互连接的生化反应模块的网络，每个模块涉及多个化学反应和各种不同的分子种类。 大自然似乎采用了某些统一的设计原则，即经过数亿年进化的生命策略，来调整反应网络模块的结构，以适应它们执行的细胞任务。该项目的目标是开发反应网络结构和反应网络行为之间关系的综合理论，从而增加对细胞功能和对环境变化的鲁棒响应的理解。这项研究需要生物学、数学和化学工程方面的专业知识，将由俄亥俄州州立大学的一个跨学科小组与以色列Rehovet的魏茨曼科学研究所的一个先驱小组合作进行。更广泛的影响：对生化网络中结构-功能关系的基本理论理解将对生物科学产生广泛的影响，并应用于特定系统的分析和新系统的设计。正如电路理论是电子工业发展的关键一样，一个精辟的生物化学电路理论预计将成为新兴学科合成生物学发展的基础，该学科旨在从生物成分中塑造新的有用设备。该项目将支持一名研究生的教育。PI开发的一个广泛传播的模拟生化反应网络的计算机程序将被更新，以反映新的理论和计算能力。它将分发给该领域的从业人员，并作为创新外联的基础，使高中和本科生参与合成生物学和分子生物工程。

Intellectual Merit: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.