Collaborative Research: Mechanisms and evolution of thermogenic capacity in high-altitude deer mice

对吸热型(“温血”)动物(如哺乳动物)来说，适应高海拔环境带来了一些最极端的挑战，这些动物强烈依赖代谢产生的热量来维持体温。代谢热的产生主要通过有氧(有氧)代谢发生，在高海拔地区氧气供应减少(低氧)可能限制维持最佳体温的能力。这项研究将以适应不同海拔的鹿鼠种群为模型，确定哪些生理机制允许它们在高海拔的低氧和寒冷条件下生存。PI将结合生理、遗传和代谢研究来识别不同海拔小鼠的潜在适应特征，并使用建模方法将这些特征整合起来，并将它们与生物体-S在不同环境中的适应能力联系起来。虽然本研究主要针对鹿鼠种群，但许多代谢调节和体温调节的分子和生理机制在哺乳动物中是高度保守的；因此，本研究的发现将对理解包括人类在内的其他哺乳动物种群对寒冷和缺氧的生理适应具有重要意义。该项目将研究与各种广泛的教育和公共宣传活动结合在一起，包括培训研究生和本科生，促进国际合作，为高中教师举办讲习班，以及在当地博物馆进行公开展示。这项研究项目的目的是确定不同海拔地区鹿鼠之间产热能力适应群体差异的机制基础。研究人员将在人工饲养的纯种小鼠身上进行共同花园驯化实验，以评估表型可塑性和基因特化在适应不同海拔中的作用。整个动物产热能力的测量将与各种从属性状的测量和潜在调控网络的功能基因组分析相结合。这种系统级分析的规模，包括复杂的建模工作，以整合一组全面的生理、遗传和代谢变量，以前从未尝试过。这项研究将对低氧和寒冷暴露的联合挑战的生理适应的机制基础产生重要的见解。这项研究涉及与加拿大麦克马斯特大学的研究人员的重要合作，他们拥有专门的专业知识，并可以使用进行某些实验所需的设施。海外合作的一个组成部分将是麦克马斯特大学为内布拉斯加-林肯大学和伊利诺伊大学厄巴纳-香槟分校的本科生提供的研究经验。本科生的研究经验得到了国际和综合活动办公室国际科学和工程科的共同资助。关于极端环境中生活的故事对公众的想象力产生了强大的吸引力，调查人员将利用这种吸引力制定一个公共外联计划，以内布拉斯加州大学州立博物馆的“周日与科学家”计划为中心。将开发面向普通公众的计划，重点是“适应极端环境”。在伊利诺伊大学厄巴纳-香槟分校，研究人员将参与一系列进化生物学研讨会，旨在帮助高中教师开发工具和有效方法，利用这项研究的例子教授进化生物学。

Adaptation to high altitude environments poses some of the most extreme challenges for endothermic ("warm-blooded") animals such as mammals that strongly depend on metabolically generated heat for maintaining the body temperature. Metabolic heat generation occurs predominantly through oxygen-dependent (aerobic) metabolism, and reduced oxygen availability (hypoxia) at high altitude may limit the capacity for maintaining of the optimal body temperature. This study will use populations of deer mice (Peromyscus maniculatus) adapted to different altitudes as a model to determine which physiological mechanisms permit them to survive under hypoxic and cold conditions of high altitudes. The PIs will use a combination of physiological, genetic and metabolic studies to identify the potentially adaptive traits in mice at different altitudes and use modeling approach to integrate these traits and link them to the organism?s fitness in different environments. Although this study focuses on the populations of deer mice, many molecular and physiological mechanisms of metabolic regulation and thermoregulation are highly conserved among the mammals; therefore, the findings of this study will have implications for understanding physiological adaptations to cold and hypoxia in high-altitude populations of other mammals including humans. This project integrates research with diverse and extensive educational and public outreach activities including training of graduate and undergraduate students, fostering international collaborations, workshops for high school teachers and public displays at a local museum. The goal of this research project is to identify the mechanistic basis of adaptive population differences in thermogenic capacity between deer mice that are native to different elevations. The investigators will conduct common-garden acclimation experiments in captive-bred, pedigreed mice to assess the roles of phenotypic plasticity and genotypic specialization in adaptation to different altitudes. Measures of whole-animal thermogenic capacity will be integrated with measures of various subordinate traits and a functional genomic analysis of the underlying regulatory networks. The scale of this systems-level analysis, which involves a sophisticated modeling effort to integrate a comprehensive set of physiological, genetic and metabolic variables, has never before been attempted. This research will yield important insights into the mechanistic basis of physiological adaptation to the combined challenges of hypoxia and cold exposure. This research involves an important collaboration with investigators at McMaster University in Canada, who have specialized expertise and access to facilities required for conduct of some experiments. A component of the foreign collaboration will be research experiences at McMaster University for undergraduate students from the University of Nebraska - Lincoln, and the University of Illinois Urbana-Champaign. The undergraduate research experiences are being supported by co-funding from the International Science and Engineering section of the Office of International and Integrative Activities. Stories about life in extreme environments exert a powerful hold on the public imagination, and the investigators will capitalize on this fascination to develop a public outreach program that is centered on the "Sunday with a Scientist" program at the University of Nebraska State Museum. Programs will be developed for the general public that will focus on 'adaptation to extreme environments'. At the University of Illinois Urbana-Champaign, researchers will be involved in a series of workshops in evolutionary biology aimed at assisting high school teachers to develop tools and effective approaches to teach evolutionary biology using examples from this research.