Coevolutionary Epidemiology of Hosts and Their Infectious Pathogens

宿主及其传染性病原体的共同进化流行病学

• 批准号: RGPIN-2022-03113
• 负责人: MacPherson, Ailene
• 金额: $ 2.11万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=758544
• 关键词: Coevolutionary; Epidemiology; Hosts; Their; Infectious

My new research program addresses fundamental questions at the intersection of evolution, ecology, and epidemiology. Inspired by the Red Queen hypothesis and the putative importance of biotic interactions in shaping diversity, the long-term goal of my research program is to characterize the emergent consequences of coevolution between hosts and their infectious pathogens. Over the next 5 years, my team will develop and apply mathematical and statistical models to support the study of infectious pathogens as model systems of coevolution via two short-term objectives: 1) Develop phylogenetic methods to characterize epidemiological mechanisms of infectious diseases, and 2) Develop population genetic models and inference methods to characterize host-pathogen coevolution in spatially structured environments. To reassess the Red Queen hypothesis in the context of directly-transmitted diseases, my team will employ complementary genomic and genetic approaches to understand feedbacks between evolutionary, epidemiological, and ecological (E3) processes. In Objective 1 we will develop a new class of methods that will allow us to characterize epidemiological mechanisms from the evolutionary relationship between pathogen genome sequences. We will then optimize these methods to infer coinfection and coevolution. Finally, we will apply these methods to cytomegalovirus, to quantify coinfection in the multimammate rat, and hence its suitability as a vector for a transmissible vaccine. In Objective 2 we will use population genetic models to understand the emergent evolutionary consequences of coevolution in spatially structured environments. Local adaptation is a powerful metric connecting theoretical and empirical understandings of coevolution. By first adapting the measurement of local adaptation for coevolution between hosts and their infectious pathogens, we will use population genetic models to assess the consequences of disease on spatial diversity. We will then use these models to develop an inferential method for identifying the strength of trade-offs between epidemiological traits, knowledge which is essential for predicting disease evolution. Finally, we will adapt this inferential framework to design and test the robustness of genomic conservation strategies for rescuing species at risk of extinction from disease. We are faced with numerous existential crises at the E3 intersection: from the unprecedented loss of biodiversity from anthropogenic environmental change and the control of zoonotic pathogens. The outcomes of the proposed research will advance genomic epidemiology and provide a theoretical framework for developing evolutionarily robust conservation strategies for wildlife populations threatened by infectious disease. My research program applies mathematical and statistical approaches to both address fundamental questions in evolution and will contribute scientific knowledge and methods to address these crises for the benefit of Canadians.

我的新研究项目涉及进化、生态学和流行病学交叉领域的基本问题。受红皇后假说和生物相互作用在形成多样性方面的重要性的启发，我的研究项目的长期目标是描述宿主与其感染性病原体之间共同进化的紧急后果。在接下来的5年里，我的团队将通过两个短期目标开发和应用数学和统计模型来支持传染性病原体作为共同进化模型系统的研究：1)发展系统发育方法来表征传染病的流行病学机制；2)发展群体遗传模型和推理方法来表征空间结构环境中宿主-病原体的共同进化。为了在直接传播疾病的背景下重新评估红皇后假说，我的团队将采用互补的基因组和遗传学方法来理解进化、流行病学和生态（E3）过程之间的反馈。在目标1中，我们将开发一类新的方法，使我们能够从病原体基因组序列之间的进化关系中表征流行病学机制。然后，我们将优化这些方法来推断共同感染和共同进化。最后，我们将把这些方法应用于巨细胞病毒，量化在多动物大鼠中的共同感染，从而确定其作为传染性疫苗载体的适用性。在目标2中，我们将使用群体遗传模型来理解空间结构环境中共同进化的紧急进化后果。局部适应是连接共同进化理论和经验理解的有力指标。通过首先调整宿主及其感染性病原体之间共同进化的局部适应测量，我们将使用群体遗传模型来评估疾病对空间多样性的影响。然后，我们将使用这些模型来开发一种推断方法，以确定流行病学特征之间权衡的强度，这对预测疾病演变至关重要。最后，我们将采用这一推理框架来设计和测试基因组保护策略的稳健性，以拯救濒临灭绝的物种。在E3的交叉点上，我们面临着许多生存危机：从人为环境变化造成的生物多样性前所未有的丧失，到人畜共患病原体的控制。该研究成果将促进基因组流行病学的发展，并为开发受传染病威胁的野生动物种群的进化稳健保护策略提供理论框架。我的研究项目应用数学和统计方法来解决进化中的基本问题，并将为加拿大人的利益贡献科学知识和方法来解决这些危机。