RoL: FELS: EAGER: A Predictive framework of metabolism as an engine of functional environmental responses across levels of biological organization

生命几乎栖息在地球的每一个角落，生物体使用不同的生存策略。尽管如此，生态学、生理学和行为的巨大多样性，生物过程是由一组高度相似的控制新陈代谢的反应推动的。在更高层次的生物组织中运作的生物过程如何从新陈代谢反应中出现，以及新陈代谢如何决定生物体对环境条件的反应，这些一般规则都是未知的。这项研究旨在解释单细胞和多细胞生物体的基本生命规则：观察到生物体的性能随着温度的变化而增加到最佳水平，之后随着温度的增加而下降（即，热性能曲线）。这项研究将检验这样一种假设，即新陈代谢对温度的反应通过生物组织的水平决定热性能曲线，最终导致生物体的生存和繁殖以及随后的种群增长。这项研究可能会对科学和社会产生更广泛的影响，因为它将提供一个实验和数学研究框架，可以应用于不同的系统，包括社会经济重要的系统，如农业，害虫和疾病物种。由于代谢的组成部分在人类和生物体之间是共享的，代谢和生物体的性能之间的基本联系将提供与代谢紊乱相关的健康问题的关键信息。该研究整合了分子，生理，生态和数学方法来测量生物体如何应对环境温度的变化。这些实验将测量热性能曲线的变化，以响应从线粒体功能到人口增长的多个生物组织水平的温度变化。这项测量将在两个经过充分研究的系统-果蝇和纤毛草履虫-中进行，以测试对温度的塑性和适应性代谢反应将通过组织水平扩大到影响种群水平的一般假设。该研究将开发一个通用的数学框架，使用一组嵌套的函数来描述因果和预测关系，这些关系将代谢反应与人口和生态系统对环境的反应联系起来。该框架旨在确定规则存在的地方，但也要发现在生物层次中出现的紧急属性。这个框架可以被在不同系统中工作的研究人员采用，以将生物组织水平上的功能性状反应联系起来，并预测他们所研究的生物体和群落如何受到环境变化的影响。实验设计明确地为未来的工作奠定了基础，这些工作将把（表型）基因组对表型组的反应联系起来，并将系统基因组学方法纳入这一框架。这项研究可能会加强研究基础设施，为广大社区的科学家在非常不同的规模的生物学工作。这一奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

Life inhabits nearly every corner of the planet, with organisms using diverse strategies to survive. Despite this, tremendous diversity in ecology, physiology, and behavior, biological processes are fueled by a set of highly similar reactions that govern metabolism. The general rules of how biological processes operating at higher levels of biological organization emerge from the reactions of metabolism and how this determines organism responses to environmental conditions are unknown. The research aims to explain a fundamental rule of life that holds across single- and multi-celled organisms: the observation that an organism's performance increases as a function of temperature to an optimal level, after which it declines as temperatures increase (i.e., the thermal performance curve). The research will test the hypothesis that the response of metabolism to temperature determines thermal performance curves through levels of biological organization, culminating in the survival and reproduction of organisms and the subsequent growth of populations. The research may have broader impact for science and society, as it will provide an experimental and mathematical research framework that can be applied to diverse systems, including socio-economically important systems, such as agricultural, pest, and disease species. Because the components of metabolism are shared between humans and the organisms studied, fundamental links between metabolism and an organism's performance will provide critical information on health issues related to metabolic disorders.The research integrates molecular, physiological, ecological, and mathematical approaches to measure how organisms respond to change in environmental temperature. The experiments will measure change in thermal performance curves in response to shifts in temperature at multiple levels of biological organization, from mitochondrial function to population growth. This measurement will be done in two well-studied systems - the fruit fly Drosophila and the ciliate Paramecium - to test the general hypothesis that plastic and adaptive metabolic responses to temperature will scale up through levels of organization to affect population-level properties such as growth rate. The research will develop a general mathematical framework using a nested set of functions to describe causal and predictive relationships that link metabolic responses up through population- and ecosystem-level responses to the environment. The framework aims to identify where rules exist, but also to discover where emergent properties arise in the biological hierarchy. This framework can be adopted by researchers working in diverse systems to link functional trait responses across levels of biological organization, and to predict how the organisms and communities that they study may be impacted by changes in the environment. The experimental design explicitly sets the stage for future work that will link (epi)genome- to-phenome responses and incorporate systems genomics approaches within this framework. The research may enhance research infrastructure for a broad community of scientists working at very different scales of biology.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.