Collaborative Research: Linking environmental challenges to the likelihood and severity of epidemics: A view through the shifting window of susceptibility

这项研究将帮助管理野生动物种群的生物学家更好地了解使疾病爆发更有可能感染、控制和传播的环境条件。生物学的一个基本目标是了解环境如何影响人类和野生动物的健康。例如，紧张的环境会使动物更容易受到感染。但很难预测或管理压力对疾病爆发的影响，因为有许多复杂的、相互作用的过程。此外，个体对压力的反应可能不同。这项研究项目将测试慢性应激是否会在动物发育的关键时期削弱免疫系统，这被称为易感的关键时间段。它将测试动物是否更容易感染，是否更容易传播感染，是否更有可能死亡。然后，这些结果将被用来测试环境应激源是否会使整个人群更有可能和更严重地爆发疾病。这项工作将有助于确定预防或减少疾病暴发的优先行动。它还将为研究动物疾病提供一个更复杂的框架。此外，研究人员将开发新的教学模块和研讨会，帮助告知州、联邦和学术科学家、土地管理人员、教师和大学生压力影响疾病结局的方式。这些项目将使用两栖动物的一种经常致命的病原体RANAV及其林蛙蝌蚪宿主作为模型系统来测试三个特定的假设：1)环境应激源增加宿主的平均易感性，2)改变易感性关键窗口的时间和持续时间，3)放大宿主之间的易感性的微小差异。一系列剂量-反应实验将确定敏感性的窗口和分布(对RANAV感染的抵抗力和耐受性)，并确定它们如何受到高盐度和温度升高的影响--这是两个相关且日益重要的环境挑战。其次，实验室实验将描述这些应激源如何影响新城疫病毒的传播。据推测，最敏感的蝌蚪也将是最具传染性的。第三，将测量最易感染和最不敏感的个体的特定生理和免疫反应，以更好地了解这些反应背后的机制。第四，将使用复杂的数学模型将这些结果转化为人口水平的结果。最后，半自然人群中的实验性流行病将被用来测试该模型的预测，即应激源如何改变关键的易感窗口，以影响RANAV流行的可能性和严重性。这一奖项反映了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。

This research will help biologists who manage wildlife populations better understand the environmental conditions that make disease outbreaks more likely to catch hold and spread. A fundamental goal in biology is understanding how the environment affects human and wildlife health. Stressful environments, for instance, can make animals more susceptible to infection. But it is difficult to predict or manage the effects of stress on disease outbreaks because there are many complex, interacting processes. In addition, individuals may not respond the same way to stress. This research project will test whether chronic stress weakens the immune system during key times in an animal's development termed 'critical windows' of susceptibility. It will test whether animals are more easily infected, better at spreading the infection, and more likely to die. These results will then be used to test whether environmental stressors make disease outbreaks more likely and severe for whole populations. This work will help prioritize actions to prevent or lessen disease outbreaks. It will also provide a more sophisticated framework for studying animal diseases. In addition, the researchers will develop new teaching modules and workshops to help inform state, federal, and academic scientists, land managers, teachers, and college students about the ways in which stress affects disease outcomes. The projects will use a ranavirus, an often-lethal pathogen of amphibians, and their wood frog tadpole hosts as model system to test three specific hypotheses: environmental stressors 1) increase the average susceptibility of hosts, 2) change the timing and duration of critical windows of susceptibility, and 3) magnify initially small differences in susceptibility among hosts. A series of dose-response experiments will characterize the windows and distribution of susceptibility (both resistance to and tolerance of ranavirus infections) and determine how they are affected by high salinity and elevated temperature - two relevant and increasingly important environmental challenges. Second, laboratory experiments will characterize how these stressors affect ranavirus transmission. It is hypothesized that the most susceptible tadpoles will also be most infectious. Third, the specific physiological and immunological responses will be measured in the most and least susceptible individuals to better understand the mechanisms underlying these responses. Fourth, a sophisticated mathematical model will be used to translate these results to population-level outcomes. Lastly, experimental epidemics in semi-natural populations will be used to test the model's predictions of how stressors alter critical windows of susceptibility to affect the likelihood and severity of ranavirus epidemics.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.