21-EEID US-UK Collab: Multi-scale infection dynamics from cells to landscapes: foot-and-mouth disease viruses in African buffalo

Infectious disease dynamics necessarily operate across biological scales: pathogens replicate within host cells and tissues; they transmit among hosts, and across host populations. As such, functional changes in host-pathogen interactions, such as those affecting pathogen vital rates or host immune responses, can generate cascading effects from molecular to landscape scales. Similarly, variation in pathogen success at larger scales generates selective pressures that feed back to shape pathogen population genetics. Linking pathogen dynamics across biological scales is thus critical to understanding evolutionary trajectories of host-pathogen systems and represents a central challenge in disease ecology.

Multi-scale models of infectious disease dynamics seek to address this challenge by linking mechanistic models representing host-pathogen interactions from cellular to population scales. Developing the mathematical tools for connecting dynamic processes operating at vastly different temporal and spatial scales has been an active focus in infectious disease modelling over recent years. These theoretical innovations have so far not been matched by empirical data generation, providing integrated data streams documenting infection processes in the same host-pathogen system, collected consistently across organizational scales. This mismatch has limited the iterative interplay between theory and data. As such, the full potential of multi-scale disease models has not been realized. If successful, these approaches could provide tools for predicting the spread and persistence of new pathogen variants in natural host populations from variant genetic or phenotypic traits - a question of immediate urgency.

In this project we will investigate viral dynamics from genomic to landscape scales using a suite of foot-and-mouth disease viruses (FMDVs) in their reservoir host, African buffalo, as a model system. FMDVs are highly contagious viruses that cause clinical disease in domestic...