INSPIRE Track 1: Maximum Entropy Production and Evolution of Complex Systems

INSPIRE奖的部分资金来自生物科学局分子和细胞生物科学部的系统和合成生物学计划和细胞动力学和功能计划，以及工程局化学、生物工程、环境和运输系统司的生物光子学计划和生物医学工程计划。智力优势：在这个INSPIRE项目中，来自几个学科的独特概念以一种新颖的方式结合在一起，为新陈代谢网络的分析、设计、构建和进化提供了一致的理论框架。首先，拟议的工作建立在代谢网络可以离散为基本途径或基本模式的前提下。细胞只能根据这些基本模式或符合质量守恒定律的模式组合发挥作用。网络的这些独特的、离散的代谢状态可以用计算工具进行严格的评估，以揭示细胞可以执行的所有可能性。由于细胞的整个性质空间是已知的，代谢网络的设计可以在完全合理的基础上进行，然后用分子生物学技术来实现。其次，最大熵产生原理(MEP)预测，当个体、离散的基本模式的使用按照玻尔兹曼分布定律分布时，达到最可能的代谢状态。第三，当根据基本模式的分布使用计算出的可预测的最可能状态与网络的当前可测量状态相比较时，可以预测在进化过程中将改变什么反应。因此，这项研究具有深远的影响，因此，需要仔细的调查来证明其普遍的有效性。如果被证明是有效的，这代表了合成生物学中的一项设计原则，为了设计出不会随着时间进一步进化的健壮、稳定的系统，需要遵循这一原则。更广泛的影响：这项研究有可能在几个重要方面改变代谢工程领域。例如，可以加强生产包括药品或生物燃料在内的有价值化学品的生物技术进程。拟议的研究还可以为二氧化碳的封存和转化为异丁醇、从生物质中生产类胡萝卜素和生物乙醇提供一个平台。它将通过为包括高中、本科生、研究生和研究生在内的下一代科学家提供高级培训，进一步影响社会。最重要的是，该项目将为科学界以新颖的方式进一步推进和应用这些开创性原则奠定基础。

This INSPIRE award is partially funded by the Systems and Synthetic Biology Program and the Cellular Dynamics and Function Program in the Division of Molecular and Cellular Biosciences in the Directorate for Biological Science; and the Biophotonics Program and Biomedical Engineering Program in the Division of Chemical, Bioengineering, Environmental, and Transport System in the Directorate for Engineering.Intellectual Merit: In this INSPIRE project, unique concepts from several disciplines are combined in a novel way to give a consistent theoretical framework for the analysis, design, construction and evolution of metabolic networks. First, the proposed work builds on the premise that metabolic networks can be discretized into fundamental pathways or elementary modes. Cells function only according to these elementary modes or combinations of modes in compliance with the mass conservation law. These unique, discrete metabolic states of a network can be rigorously evaluated with computational tools to reveal all the possibilities that a cell can perform. Because the entire property space of a cell is known, the design of a metabolic network can be carried out on a completely rational basis and then implemented with molecular biology techniques. Second, the Maximum Entropy Production principle (MEP) predicts that the most probable metabolic state is reached when the usage of the individual, discrete elementary modes is distributed according to the Boltzmann distribution law. Third, when the predictable most probable state, which is computed from the distributed usage of elementary modes, is compared with the current measurable state of the network, it is possible to predict what reaction will be altered during the course of evolution. Thus, this research has far reaching implications and, therefore, requires careful investigation to prove its general validity. If proven to be valid, this represents a design principle in synthetic biology that needs to be followed in order to engineer robust, stable systems that do not evolve further in time. Broader Impacts: This research has the potential to transform the field of metabolic engineering in several significant ways. For example, biotechnology processes that produce valuable chemicals, including pharmaceuticals or biofuels, may be enhanced. The proposed study could also provide a platform for the sequestration and transformation of carbon dioxide into isobutanol, the production of carotenoids and bioethanol from biomass. It would further impact society by providing advanced training to the next generation of scientists, including high school, undergraduates, graduate, and post-graduate students. Most importantly, the project would lay the foundation for the scientific community to further advance and apply these groundbreaking principles in novel ways.