Linking host energetics and multiple host defenses to transmission and virulence evolution

项目摘要 病原体性状的进化，如毒力和传播，构成了越来越多的 对基础生物学和应用生物学提出了严峻的挑战。从根本上讲， 塑造疾病的严重性和传播以及这些特征的演变， 破坏减轻疾病的策略（例如，疫苗、药物、饮食）。预测毒力 进化仍然具有挑战性，在很大程度上，因为最重要的驱动力之一， 病原体的进化、宿主的防御机制仍然知之甚少。多主机防御 机制强烈决定病原体的生产（在宿主内），从而传播 在人口水平上的主机之间。因此，主机内和主机间进程 最终控制着病原体的进化然而，宿主的防御机制及其对 传播也很难解开。宿主防御的能量消耗很大， 彼此之间以及与宿主生理学的其它方面（例如，生长、繁殖）， 宿主基因型，并且对环境条件敏感（例如，资源可用性）。更好 对宿主内过程及其对传播的影响的了解将大大有助于 提高我们将这些不同规模的生物组织与病原体进化联系起来的能力。 最近的理论表明，这种跨尺度的联系可以提供关键的洞察病原体 进化然而，到目前为止，这一理论还没有得到实证检验。 我们建议确定主机能量学和多个 宿主的防御机制决定了毒力和传播的进化。这个项目 整合（i）新的能量和进化理论的发展与（ii）个人和 种群水平的实验，使用模型宿主-病原体系统，大型蚤和 多枝巴氏杆菌（为了利用该系统众所周知的遗传和环境变异， 宿主防御和严格测试理论预测）。该积分将确定（1） 不同寄主防御机制对病原菌产生的独特和复合作用; 资源可利用性的环境变化如何影响宿主防御策略、病原体 生产，毒力和传播;（3）是否了解机制 宿主内部和宿主之间的联系提高了我们准确预测病原体的能力 在不同的环境和遗传背景下进化。我们将开发 明确整合资源（宿主饮食）和宿主内以及宿主之间的数学模型- 宿主动态预测流行病学和进化动态（毒力和传播 进化）。

PROJECT SUMMARY The evolution of pathogen traits such as virulence and transmission poses an increasingly formidable challenge to basic and applied biology. Virulence and transmission fundamentally shape the severity and spread of disease and the evolution of these traits frequently undermines strategies to mitigate disease (e.g., vaccines, drugs, diet). Predicting virulence evolution remains challenging, in large part, because one of the most important drivers of pathogen evolution, host defense, remains poorly understood. Multiple host defense mechanisms strongly determine pathogen production (within hosts) and thus transmission between hosts at the population-level. Hence, both within-host and between-host processes ultimately govern pathogen evolution. Yet, host defense mechanisms and their effects on transmission are also difficult to unravel. Host defenses are energetically costly, interfere with one another and with other aspects of host physiology (e.g., growth, reproduction), vary across host genotypes, and are sensitive to environmental conditions (e.g., resource availability). Better understanding of within-host processes and their effects on transmission will substantially improve our ability to link these different scales of biological organization to pathogen evolution. Recent theory suggests that such cross-scale links can provide key insight into pathogen evolution. To date, however, this theory has not been tested empirically. We propose to identify how fundamental interactions between host energetics and multiple host defense mechanisms shape the evolution of virulence and transmission. This project integrates (i) the development of novel energetic and evolutionary theory with (ii) individual and population-level experiments using a model host-pathogen system, Daphnia magna and Pasteuria ramosa (to leverage this system’s well-known genetic and environmental variation in host defense and rigorously test theoretical predictions). This integration will determine (1) the unique and composite effects of different host defense mechanisms on pathogen production; (2) how environmental variation in resource availability affects host defense strategies, pathogen production, virulence, and transmission; and (3) whether understanding mechanistic connections within and between hosts improves our ability to accurately predict pathogen evolution across different environmental and genetic backgrounds. We will develop mathematical models that explicitly integrate resources (host diet) and within-host and between- host dynamics to predict epidemiological and evolutionary dynamics (virulence and transmission evolution).