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

该项目解决了生物学中两个长期存在的问题，即基因组如何成为表型组，以及生物体如何通过变化保持稳定，通过调查身体大小如何影响陆生哺乳动物的免疫防御。虽然身体质量是对许多生理特征的最强影响之一，但身体大小对免疫系统的影响尚不清楚。通过一种前所未有的比较方法，该研究测试了身体大小是否解释了为什么一些物种更容易受到寄生虫的影响，更有可能成为寄生虫的宿主，而其他物种则具有抵抗力。具体来说，这项研究将提供新的信息，说明先天免疫的功能形式如何与150种动物园饲养的陆地哺乳动物物种的体型相关，这些哺乳动物的体型范围很广。结果将提供一个框架，了解哺乳动物的免疫变异有可能提高疾病传播的模型，通过提供预测的免疫防御水平的物种从未研究过。该项目为两名年轻的研究人员、一名博士后研究人员和8-10名本科研究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发外展活动，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理解人类和动物健康相关。该项目调查体重是否以及如何与陆生哺乳动物的抗菌免疫防御体系结构相关，这是规模缩放的一个未研究的方面。宿主的大小可能影响i）暴露于感染性生物体的机会，ii）免疫防御跟上病原体复制的能力，iii）宿主监测机制在相对较大的风险空间中检测威胁的能力。该项目将确定先天免疫的功能形式如何与150种动物园饲养的陆地哺乳动物的身体大小相关，这些哺乳动物的身体质量跨越7个数量级。此外，将量化10种灵长类动物中先天免疫防御的蛋白质表达作为体重的函数，跨越5个数量级的大小。使用动物园圈养的动物，在共同的环境中经历类似的发育历史，最大限度地减少了野生个体研究中固有的混淆变量的影响。测量功能性抗微生物反应优于不太直接的宿主防御测定。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。该项目解决了生物学中的两个重大挑战，并有可能改变科学家对宿主-寄生虫相互作用的看法。所产生的转录组数据将有助于其他系统生物学研究，包括了解大小如何限制脊椎动物调控过程的进化。包括8-10名本科生在内的参与者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.