Quasispecies Network Theories for the Cross Scale Evolutionary Dynamics of Pathogens

该项目将建立一个理论框架，以了解病毒病原体的内在变异性，以及如何从普遍的宿主免疫反应中逃脱的进化，在生物组织的各个层面上发展。目标是整合从宿主内的病毒准种进化，通过宿主社会传播网络，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，并辅以案例研究；由此产生的理论将用于探索选择工作的综合规模，跨越一系列重要的急性和慢性病毒病原体。从分子水平到大陆尺度，理解跨整体尺度或组织水平的动力学是理论生物学的一个关键前沿。传染病为探索这些想法提供了特别肥沃的土壤。使这个问题具有挑战性和引人入胜的是，通过自然选择的压力，从蛋白质到流行病再到其他尺度的适应性反馈。该项目将开发和传播理论工具，以探索这些动态，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运行疾病动力学的跨学科研讨会。为物理、生物专业本科生提供暑期研究机会；每个学生将被要求在“其他”学科中开发一个项目。

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.