Design Principles of Biochemical Reaction Networks

智力价值：单个活细胞的生物学基础是一种极其复杂的生化机制，它允许细胞执行复杂的新陈代谢功能，对外部信号做出准确的反应，并即使在剧烈波动的环境中也能忠实地复制自己。这台机器由相互连接的生化反应模块组成的网络，每个模块都涉及多个化学反应和各种不同的分子物种。大自然似乎采用了某些统一的设计原则--经过数亿年演变而来的生命策略，以调整反应网络模块的结构，以适应它们执行的细胞任务。该项目的目标是发展反应网络结构和反应网络行为之间关系的全面理论，从而增加对细胞如何发挥作用和对环境变化做出强有力响应的理解。这项研究需要生物学、数学和化学工程方面的专业知识，并将由俄亥俄州立大学的一个跨学科团队与以色列雷霍维市魏兹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影响，应用于特定系统的分析和新系统的设计。就像电路理论是电子工业发展的关键一样，精辟的生化电路理论有望成为合成生物学这一新兴学科发展的基础，合成生物学试图从生物成分中制造出新的有用的设备。该项目将支持研究生的教育。由PI开发的用于模拟生化反应网络的广泛传播的计算机程序将进行更新，以反映新的理论和计算能力。它将传播给该领域的从业者，并作为创新推广的基础，使高中生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.