Collaborative Research: Constraints of biomass on innate immunity across terrestrial mammals

该项目通过研究体型如何影响陆生哺乳动物的免疫防御，解决了生物学中两个长期存在的问题，即基因组如何成为现象，以及生物体如何通过变化保持稳定性。虽然体重是对许多生理特征影响最大的因素之一，但对免疫系统的影响还不为人所知。通过一种前所未有的比较方法，该研究测试了体型是否解释了为什么一些物种对寄生虫更敏感，更有可能成为寄生虫宿主，而其他物种则有抵抗力。具体来说，这项研究将为150种不同体型的动物园饲养的陆生哺乳动物的先天免疫功能形式与体型之间的关系提供新的信息。研究结果将为理解哺乳动物免疫变异提供一个框架，有可能通过预测从未研究过的物种的免疫防御水平来增强疾病传播模型。该项目为两名青年研究员、一名博士后研究员和8-10名本科生提供职业发展机会。参与者将为动物园和当地初中和高中的生物课开展推广活动，以提高动物园展览和课程计划的教育效果。这些活动将展示比较研究如何与了解人类和动物健康相关。本项目研究体重是否以及如何与陆生哺乳动物的抗微生物免疫防御体系相关，这是一个尚未研究的尺寸缩放方面。宿主大小可能影响1)接触感染性生物的机会，2)免疫防御跟上病原体复制步伐的能力，3)宿主监测机制在相对较大的风险空间中发现威胁的能力。该项目将确定150种动物园饲养的陆生哺乳动物的先天免疫功能形式与体重之间的关系，这些动物的体重有7个数量级。此外，将对10种灵长类动物的先天免疫防御蛋白表达与体重的关系进行量化，这些灵长类动物的体型大小为5个数量级。使用动物园饲养的动物，它们在普通环境中经历了相似的发育历史，最大限度地减少了野生个体研究固有的混杂变量的影响。测量功能性抗菌反应比不太直接的宿主防御测定更可取。转录组学方法将显示哪些先天免疫基因、基因网络和/或基因模块对体重最敏感。该项目解决了有机体生物学中的两大挑战，并有可能改变科学家对宿主-寄生虫相互作用的看法。生成的转录组学数据将有助于其他系统生物学的研究，包括理解大小如何限制脊椎动物调节过程的进化。参与者，包括8-10名本科生，将为动物园开发解释性展示和展览，并为初中和高中生物课制定课程计划，以吸引和教育学生和公众，并展示比较研究的相关性。

This project addresses two long-standing questions in biology, how genomes become phenomes and how organisms maintain stability through change, by investigating how body size affects immune defenses in terrestrial mammals. Although body mass is one of the strongest influences on many physiological traits, effects of body size are not known for immune systems. Through an unprecedented comparative approach, the research tests whether body size explains why some species are more susceptible to parasites and more likely to act as parasite reservoirs, whereas other species are resistant. Specifically, the research will provide new information on how functional forms of innate immunity relate to body size among 150 zoo-housed terrestrial mammal species spanning a broad range of sizes. Results will provide a framework for understanding of mammalian immune variation has the potential to enhance models of disease spread by providing predictions about the level of immune defense expected in species never before studied. The project fosters career development for two young investigators, a postdoctoral researcher, and 8-10 undergraduate research students. Participants will develop outreach activities for zoos and for biology classes at local middle and high schools, to enhance the educational effectiveness of zoo exhibits and lesson plans. These activities will demonstrate how comparative research is relevant to understanding human and animal health.This project investigates whether and how body mass is related to the architecture of antimicrobial immune defenses in terrestrial mammals, an unstudied aspect of size-scaling. Host size likely affects i) the chance of exposure to infectious organisms, ii) the ability of immune defenses to keep pace with pathogen replication, iii) the ability of host surveillance mechanisms to detect threats in a comparatively large risk space. The project will determine how functional forms of innate immunity relate to body size among 150 zoo-housed species of terrestrial mammals spanning 7 orders of magnitude in body mass. In addition, protein expression for innate immune defenses as a function of body mass among 10 primate species spanning 5 orders of magnitude in size will be quantified. Using zoo-housed animals, which experience similar developmental histories in common environments, minimizes effects of confounding variables inherent to the study of wild individuals. Measuring functional antimicrobial responses is preferable to less direct assays of host defense. The transcriptomic methods will show which innate immune genes, gene networks, and/or gene modules are most sensitive to body mass. This project addresses two Grand Challenges in Organismal Biology, and has the potential to transform how scientists think about host-parasite interactions. The transcriptomic data generated will contribute to other systems biology pursuits, including understanding how size may constrain the evolution of regulatory processes in vertebrate animals. The participants, including 8-10 undergraduates, will develop interpretive displays and exhibits for zoos, and lesson plans for middle- and high-school biology classes to engage and educate students and the public and to demonstrate the relevance of comparative research.