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

在自然界中，人类与野生动物的接触与野生动物中更大的病毒负担相关，因此与新的病毒病原体蔓延到人类种群的风险更高。然而，造成这种风险的因素仍然知之甚少，特别是在高度流动但拥挤的动物种群中，如洞穴蝙蝠。该项目使用埃及果蝠作为研究系统，试图了解食物获取、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，以控制与人类接触不同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，并增强预测病毒从蝙蝠蔓延到其他野生动物或人类的风险的能力。该项目还将通过实施名为“来自蝙蝠洞穴--本科生综合疾病研究”的创新主动学习体验，对教育和培训产生更广泛的影响，博士后研究人员将学习应用综合研究和指导方法，让本科生队列参与研究，并通过GBatNet(国家科学基金会资助的BAT研究小组的国际网络)进行同行指导。人类对环境的破坏被认为是野生动物种群疾病出现的核心原因，因为它减少了动物赖以生存的食物和避难所的可获得性，从而给动物带来压力，使它们更容易受到病毒的影响。然而，管理环境、野生动物宿主及其支持的病毒社区之间关系的机制鲜为人知。为了解决这个问题，该项目将利用单一的埃及果蝠(Rousettus Aegyptiacus)野生系统，从洞穴中采集不同性别、年龄和生殖条件的动物，这些洞穴支持不同数量的蝙蝠，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包围。以每只蝙蝠为观察单位，分析将致力于将景观资源、个体状况和免疫力与病毒图谱联系起来，从而回答三个关键问题：(1)宿主丰度、繁殖、年龄和状况如何以不同或相互作用的方式影响病毒多样性；(2)分子免疫机制如何对野生种群中的环境和生理应激做出反应；以及(3)基因表达图谱和病毒感染在野外如何相互影响？这些结果应该能够识别出通过生物条件将人类干扰的环境梯度与病毒体多样性联系起来的联系，从而为理解野外疾病动态、模拟风险并从而预防下一次大流行提供必要的新信息。此外，该项目研究疾病出现的基本过程的集成和机械系统方法预计将在人-野生动物疾病界面上跨分类群推广。该奖项反映了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。

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.