Quasispecies Network Theories for the Cross Scale Evolutionary Dynamics of Pathogens

该项目将开发一个理论框架，以了解病毒病原体的内在变异性，从而了解逃避普遍宿主免疫反应的进化是如何在生物组织水平上发展的。其目标是通过宿主社会传播网络整合从宿主内的病毒准种进化到种群水平的流行病和病毒进化的动态。所需的理论框架将通过分析方法得出，并得到案例研究的支持；由此产生的理论将用于探索在一系列重要的急性和慢性病毒病原体上进行选择的综合规模。从分子水平到大陆水平，理解跨综合尺度或组织水平的动力学是理论生物学的一个关键前沿。传染病是探索这些想法的特别肥沃的土壤。使这个问题具有挑战性和吸引力的是通过自然选择的压力，跨范围的适应性反馈--从蛋白质到大流行，再到回归。该项目将开发和传播探索这些动态的理论工具，并将其应用于从流感到逆转录病毒等一系列重要病原体。研究将通过宾夕法尼亚州立大学传染病动力学跨学科中心，与本科生和博士后研究人员的跨学科培训紧密结合。博士后研究人员将组织和举办疾病动力学方面的跨学科研讨会。将为物理和生物专业的本科生提供暑期研究机会；每个学生将被要求开发一个其他学科的项目。

This project will develop a theoretical framework to understand how the inherent variability of viral pathogens, and hence the evolution of escape from prevailing host immune responses, develops across levels of biological organization. The goal is to integrate dynamics from viral quasispecies evolution within hosts, through host social transmission networks, to population level epidemics and viral evolution. The required theoretical framework will be derived via analytical approaches, bolstered by case studies; the resulting theory will be used to explore the integrative scale at which selection works, across a range of important acute and chronic viral pathogens. Understanding dynamics across integrative scales or levels of organization, from the molecular level to the continental scale, is a key frontier of theoretical biology. Infectious diseases represent particularly fertile ground for exploring these ideas. What makes the problem challenging and fascinating is the adaptive feedback across scales - from protein to pandemic and back - through the pressures of natural selection. The project will develop and disseminate theoretical tools to explore these dynamics and apply them to a range of important pathogens, from influenza to retroviruses. Research will be tightly integrated to interdisciplinary training of undergraduates and postdoctoral researchers through Pennsylvania State University's interdisciplinary Center for Infectious Disease Dynamics. Postdoctoral researchers will organize and run interdisciplinary workshops in disease dynamics. Summer research opportunities will be provided for undergraduates majoring in physics and biology; each student will be required to develop a project in the 'other' discipline.