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，生物使用各种各样的策略来生存。尽管如此，在生态学、生理学和行为学上存在着巨大的多样性，但生物过程是由一系列高度相似的控制新陈代谢的反应推动的。生物过程如何在更高层次的生物组织中从代谢反应中产生，以及这如何决定生物体对环境条件的反应的一般规则尚不清楚。该研究旨在解释单细胞和多细胞生物的基本生命规律：观察到生物体的性能随着温度的增加而达到最佳水平，之后随着温度的增加而下降（即热性能曲线）。这项研究将验证这样一种假设，即新陈代谢对温度的反应决定了生物组织水平的热性能曲线，最终决定了生物体的生存和繁殖以及随后的种群增长。这项研究可能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，包括社会经济上重要的系统，如农业、病虫害物种。由于新陈代谢的组成部分在人类和所研究的生物体之间是共享的，新陈代谢和生物体性能之间的基本联系将为与代谢紊乱有关的健康问题提供关键信息。该研究综合了分子、生理、生态和数学方法来测量生物体如何对环境温度变化做出反应。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等多个生物组织水平的温度变化。这项测量将在两个被充分研究过的系统中进行——果蝇和纤毛虫草履虫——以测试一个普遍的假设，即对温度的可塑性和适应性代谢反应将通过组织水平扩大规模，从而影响种群水平的特性，如生长速度。这项研究将开发一个通用的数学框架，使用一套嵌套的函数来描述通过种群和生态系统水平对环境的反应将代谢反应联系起来的因果关系和预测关系。该框架旨在确定规则存在的位置，同时也发现在生物层次结构中出现的紧急属性的位置。这一框架可以被研究不同系统的研究人员采用，以联系跨生物组织水平的功能性状反应，并预测他们研究的生物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，这些工作将连接（epi）基因组对表型的反应，并将系统基因组学方法纳入该框架。这项研究可能会为从事不同生物学研究的广大科学家群体加强研究基础设施。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.