Collaborative Research: The Evolution of Pathogen Virulence in Experimental Metapopulations

引起疾病的生物体通常具有在相对较短的时间内可能发生进化变化的特征。多药耐药细菌的增加和宿主的转换（例如，疾病从动物转移到人类）是特别显著的例子。尽管进化变化很重要，但大多数流行病学模型都假设病原体不会改变。该项目结合了数学和实验方法来研究细分种群（即元种群）中病原体的进化动力学。使用模型宿主-病原体系统（细菌作为宿主，病毒感染细菌作为病原体），宿主/病原体在大量亚群之间的运动模式将被实验操纵，病原体的进化将被监测。将这些实验与基于经验的数学模型相结合，将能够评估寄主-病原体种群的结构如何影响病原体的进化。特别是，病原体的毒力（即它杀死宿主的速度有多快）将是研究的重点，因为毒力的进化可能密切依赖于宿主相互接触的方式。这项工作具有一系列更广泛的影响。一个目标是利用这个系统作为博士后、研究生和本科生的教育工具。此外，实验系统将被改编为高等本科课程的教学工具。将积极征聘代表性不足的少数民族和妇女参与拟议的研究。最后，提出的工作可能会突出群体结构的微妙方面如何有利于人类病原体的不同进化路径。这些信息将对公共卫生管理产生重要影响。

Organisms that cause disease often possess features that make evolutionary change likely over relatively short periods of time. The rise of multi-drug resistant bacteria and the switching of hosts (e.g., diseases shifting from animals to humans) are particularly notable examples. Despite the importance of evolutionary change, most epidemiological models assume that pathogens do not change. This project combines mathematical and experimental approaches to study the evolutionary dynamics of pathogens in subdivided populations (i.e., metapopulations). Using a model host-pathogen system (bacteria as hosts and viruses infecting bacteria as pathogens'), the pattern of host/pathogen movement between a large set of subpopulations will be experimentally manipulated and evolution of the pathogen monitored. Pairing these experiments with empirically-based mathematical models will allow an assessment of how the structure of the host-pathogen population influences the evolution of the pathogen. In particular, virulence in the pathogen (i.e., how quickly it kills its host) will be the focus of the research, as the evolution of virulence may depend intimately on the manner by which hosts contact one another.This work has a range of broader impacts. One goal is the use of this system as an educational tool for postdoctoral, graduate and undergraduate students. In addition, the experimental system will be adapted to serve as a teaching tool within upper-level undergraduate courses. Underrepresented minorities and women will be actively recruited for involvement in the proposed research. Finally, the proposed work may highlight how subtle aspects of population structure could favor different evolutionary paths in human pathogens. Such information would carry important implications for public health management.