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

RoL：FELS：EAGER：新陈代谢的预测框架，作为跨生物组织层次的功能性环境响应的引擎

基本信息

批准号：
1838098
负责人：
Kristi Montooth
金额：
$ 30万
依托单位：
University of Nebraska-Lincoln
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1838098&HistoricalAwards=false
关键词：
RoL FELS EAGER Predictive framework

项目摘要

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.

生命几乎栖息在地球的每一个角落，有机体使用不同的策略生存。尽管如此，生态、生理和行为的巨大多样性，生物过程是由一组高度相似的新陈代谢反应推动的。生物过程如何在更高水平的生物组织中运行，如何从新陈代谢的反应中产生，以及这如何决定生物对环境条件的反应，这些一般规则尚不清楚。这项研究旨在解释一个存在于单细胞和多细胞生物体中的基本生命规律：观察到生物体的性能作为温度的函数增加到最佳水平，然后随着温度的升高而下降(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，可应用于不同的系统，包括重要的社会经济系统，如农业、虫害和疾病物种。因为新陈代谢的成分在人类和被研究的生物体之间是共享的，新陈代谢和生物体表现之间的基本联系将提供与新陈代谢紊乱相关的健康问题的关键信息。这项研究综合了分子、生理、生态和数学方法来测量生物对环境温度变化的反应。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种群增长的多个生物组织水平的温度变化。这项测量将在两个研究得很好的系统--果蝇和纤毛虫草履虫--中进行，以检验对温度的塑料和适应性新陈代谢反应将通过组织水平扩大到影响种群水平的属性，如增长率的普遍假设。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因果关系和预测关系，这些关系通过种群和生态系统对环境的反应将代谢反应联系起来。该框架旨在确定规则存在的位置，但也要发现生物层次结构中出现的新特性。这个框架可以被在不同系统中工作的研究人员采用，以将不同生物组织水平的功能特征反应联系起来，并预测他们研究的有机体和群落可能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(EPI)基因组到表观基因组的反应联系起来，并将系统基因组学方法纳入这个框架。这项研究可能会为在非常不同规模的生物学领域工作的广大科学家加强研究基础设施。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。