Dissertation Research: Within-host seasonal drivers of pathogen dynamics in a fruit bat reservoir

疾病通常有规律的模式：例如，通常有一个流感季节，麻疹和水痘的发生有规律的周期是众所周知的。解释通常涉及宿主(人)的运动和接触模式。该项目将研究其他因素，如宿主状况的季节性变化(例如，营养或生殖状况)如何影响疾病的传播。这项研究的重点是蝙蝠，它们是许多疾病的已知或疑似宿主和宿主。更多地了解宿主对疾病的耐受性对于预测和预防新的传染病至关重要。结果将提高对疾病风险和传播的了解，并对人类健康产生直接影响。研究人员将继续与马达加斯加的科学家合作，为该国的人类和野生动物健康和保护做出贡献。该奖项将促进博士生的教育和培训，支持她开发一种新的宿主条件衡量标准和改进的疾病动力学模型。这位博士生将开发一门疾病动力学建模课程，并将继续邀请本科生参与这项研究。研究人员假设，脂肪组织的季节性波动是宿主对一系列不同的病毒、细菌和原虫感染耐受病原体的策略的基础。脂肪组织可能通过调节细胞内自噬过程来介导病原体诱导的细胞内损伤和促进修复。这一规定将促进宿主对感染的耐受性。在资源稀缺的冬季，肥胖的减少可能会导致自噬过程中功能的下降，从而允许细胞内病原体诱导的损伤积累，从而需要免疫抵抗。研究人员将使用在对马达加斯加三种地方性果蝠进行为期18个月的病原体动态实地研究期间收集的血清样本来验证这些假设。他们将对数据集中每只蝙蝠的血清样本进行瘦素的酶免疫分析，以量化肥胖程度。瘦素是一种由脂肪组织分泌的神经内分泌信号荷尔蒙。关于肥胖的数据将被用来对一种新的、宿主内的模型进行参数化，以探索脂肪组织对病原体损害控制的贡献。尽管季节性接触模式经常捕捉到人类感染的流行动态，但它们不足以解释病原体的持久性以及在包括蝙蝠在内的一些重要野生动物宿主中观察到的疾病传播的季节性。

Diseases often follow regular patterns: there is commonly a flu season, for example, and regular cycles in the occurrence of measles and chicken pox are well known. Explanations usually involve patterns of host (human) movement and contact. This project will examine how other factors such as seasonal changes in host status (nutritional or reproductive status, for example) influence the spread of disease. The research focuses on bats, which are known or suspected hosts and reservoirs for a number of diseases. Understanding more about host tolerance to disease will be critical to predicting and preventing new infectious diseases. Results will improve understanding of disease risk and spread, with direct consequences for human health. The researchers will continue to work with scientists in Madagascar, contributing to human and wildlife health and conservation in that country. The award will advance the education and training of a doctoral student, supporting her to develop a new measure of host condition and improved models for disease dynamics. The doctoral student will develop a course in modeling disease dynamics and will continue to engage undergraduate students in the research. The researchers hypothesize that seasonal fluctuations in adipose tissue underlie a host's strategy of pathogen tolerance versus resistance for a diverse suite of viral, bacterial, and protozoan infections. Adipose tissues may mediate pathogen-induced intracellular damage and promote repair by regulating processes of intracellular autophagy. This regulation would promote host tolerance to infection. During resource-scarce winters, reductions in adiposity could lead to declining function in autophagic processes, allowing for accumulation of intracellular pathogen-induced damage that necessitates immune resistance. The researchers will test these hypotheses using serum samples collected during an 18-month field study of pathogen dynamics in three endemic fruit bats in Madagascar. They will conduct enzyme-immunoassays for leptin, a neuroendocrine signaling hormone secreted by adipose tissue, in serum samples of each individual bat in the dataset to quantify adiposity. Data on adiposity will be used to parameterize a new, within-host model exploring adipose tissue contributions to pathogen damage control. Although seasonal contact patterns often capture epidemic dynamics in human infections, they are insufficient to explain pathogen persistence, and the observed seasonality of disease transmission, in a number of important wildlife hosts, including bats.