Understanding and predicting viral evolution

A key problem with viral infections is the on-going evolution of the virus. This is particularly true for RNA viruses and retroviruses as they have error-prone polymerases. Viral evolution can lead to immune escape, vaccine escape and drug resistance. It is therefore essential that we understand the viral evolution and develop methods to predict evolutionary trajectories.

Fortunately, evolutionary change is not without limits. Viral proteins must be expressed at the appropriate level, fold up to make appropriate three-dimensional structures and form the correct binding and active sites. All of these requirements constrain viral evolution, limiting the envelope of allowed sequences. In this project we aim to understand and quantify these constraints. We will use available information on sequence variation from a range of pathogens. We will put this in the appropriate phylogenetic and structural context, and identify patterns and limits on change. We will develop computational tools to predict the likely limits on the future course of viral evolution. These predictions will be tested against new sequencing data that describes on-going viral outbreaks.

Understanding and predicting viral evolution is a problem of fundamental biology, with wide applications to both human and animal diseases. It also advances our understanding of constraints on evolution in other biological systems. We will be developing novel computational technologies and methodologies, and this project fits squarely within 'World Class Bioscience.'