Quasispecies Network Theories for the Cross Scale Evolutionary Dynamics of Pathogens

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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.