IntBIO: Collaborative Research: Integrated mechanisms of environment-host-virome interactions

在自然界中，人类与野生动物之间的接触与野生动物中更大的病毒负担相关，因此与新病毒病原体溢出到人群中的风险更高相关。然而，导致这种风险的因素仍然知之甚少，特别是在高度移动的，但密集的动物种群，如穴居蝙蝠。使用埃及果蝠作为研究系统，该项目旨在了解获得食物，整体动物健康和对免疫挑战的反应等因素如何在野外相互影响，以控制暴露于人类的人群中病毒感染的程度。该项目将使用高度综合的方法来阐明疾病风险的基本生物学，并提高预测蝙蝠对其他野生动物或人类的病毒溢出风险的能力。 该项目还将对教育和培训产生更广泛的影响，方法是实施一种创新的主动学习经验，称为“来自蝙蝠洞穴-本科生综合疾病研究”，博士后研究人员将学习应用综合研究和指导方法，通过GBatNet（一个由国家科学基金会资助的蝙蝠研究团体国际网络）让本科生群体参与研究和同行指导。 人类对环境的破坏被认为在野生动物种群出现疾病方面发挥了核心作用，因为它减少了动物所依赖的食物和避难所的可用性，从而使动物感到压力，使它们更容易感染病毒。然而，管理环境，野生动物宿主和它们支持的病毒群落之间关系的机制知之甚少。为了解决这个问题，该项目将利用埃及果蝠（Rousettus aegyptiacus）的单一凝聚力野生系统，从支持不同数量蝙蝠的洞穴中采样不同性别，年龄和生殖条件的动物，受到不同程度的狩猎，并被不同质量的觅食栖息地和食物资源所包围。以每一只蝙蝠为观察单位，分析的目的是将景观资源、个体状况和免疫力与病毒谱联系起来，从而回答三个关键问题：（1）宿主丰度、繁殖、年龄和状况如何差异或相互作用地影响病毒多样性;（2）野生种群的分子免疫机制如何对环境和生理压力作出反应;以及（3）基因表达谱和病毒感染在野外是如何相互影响的？ 这些结果应该可以识别出人类干扰的环境梯度与病毒组多样性之间的联系，从而为了解野生疾病动态，建模风险提供重要的新信息，从而防止下一次大流行。此外，该项目的综合和机械系统的方法来研究疾病出现的基本过程，预计将在人类-野生动物疾病接口的类群中推广。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

In nature, encounters between humans and wildlife correlate with greater viral burdens in wildlife and therefore with higher risk of new viral pathogens spilling over into human populations. Yet, the factors contributing to this risk remain poorly understood, especially among highly mobile, but tightly packed populations of animals, such as cave-dwelling bats. Using the Egyptian fruitbat as a study system, this project seeks to understand how factors such as access to food, overall animal health, and responses to immune challenges influence each other in the wild to control the degree of viral infection in populations experiencing variable exposure to humans. The project will use highly integrative approaches to illuminate the fundamental biology of disease risk and to enhance the capacity to predict risks of viral spillover from bats to other wildlife or to humans. The project will also have broader impact on education and training by implementing an innovative active-learning experience, called “From the Bat Cave – Integrative Disease Research for Undergraduates”, in which postdoctoral researchers will learn to apply integrative research and mentoring methods to involve cohorts of undergraduate students in research and peer-peer mentoring through GBatNet, a NSF-funded international network of bat research groups. Human disruption of the environment is thought to play a central role in disease emergence in wildlife populations by reducing the availability of foods and refuge that animals rely upon, thereby stressing the animals and making them more susceptible to viruses. However, the mechanisms governing relationships among the environment, the wildlife host, and the viral communities they support are poorly known. To address this problem, the project will take advantage of a single cohesive wild system of Egyptian fruit bats (Rousettus aegyptiacus) to sample animals of different sex, age, and reproductive condition from caves that support different numbers of bats, are subject to variable levels of hunting, and are surrounded by different qualities of foraging habitat and hence food resources. Using each individual bat as the unit of observation, analyses will aim to relate landscape resources, and individual condition and immunity to viral profiles, thus answering three key questions: (1) how do host abundance, reproduction, age, and condition differentially or interactively influence viral diversity; (2) how do molecular immune mechanisms respond to environmental and physiological stressors in wild populations; and (3) how do gene expression profiles and viral infection influence one another in the wild? The results should allow links to be discerned that connect environmental gradients of human disturbance to virome diversity via organismal conditions, thereby providing essential new information for understanding disease dynamics in the wild, modeling risks, and thus preventing the next pandemic. Moreover, the project’s integrated and mechanistic systems approach to studying fundamental processes in disease emergence is expected to be generalizable across taxa at the human-wildlife disease interface.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.