BM, PhD, FRCPath, FRS(E)
Professor of Virology
My principal research interest and focus has been in the evolution and epidemiology of virus infections, and interactions with their hosts. This has led to a variety of research investigations ranging from evolutionary studies of virus variability and recombination, molecular epidemiology and investigations of viral pathogenesis and interactions of virus with host cell defences.
Viral pathogenesis. Recent research has been focussed on the characterisation of RNA secondary structure in viruses, and its effect on virus evolution. Discovery of large scale RNA structure in many families of positive-stranded RNA viruses has been based upon the development of large-scale bioinformatic methods to quantify and characterise RNA secondary structure formation in viral genomes. The association of genome-scale organised RNA structure (GORS) with host persistence, and the finding that their genomes are structured in a fundamentally different way from those causing acute infections has been the subject of ongoing investigations of the nature of virus interactions with host cell defences modulated by double-stranded RNA, the physical structure of the predicted RNA structures and the influence of RNA structure as a sequence constraint on the evolution of persistent viruses.
Recently, this work had progressed in the investigational of the evolutionary and functional basis for the pervasive suppression of CpG and UpA dinucleotides in RNA viruses. Modelling evidence for selection against them in cytoplasmically-expressed RNA sequences and the discovery that viruses with high frequencies of CpG/UpA are recognised and suppressed by as yet uncharacterised intrinsic defence mechanisms suddenly opens exciting, new areas of enquiry into innate immunity in mammalian cells. Conversely, accelerated replication of viruses with suppressed frequencies confronts us with a seeming evolutionary paradox only resolvable through re-evaluation of relationships between disease processes and transmission dynamics.
Molecular Evolution and Epidemiology. A second area of research focuses on the molecular epidemiology, evolution and emergence of a wide range of human pathogenic viruses. Through the development of methods to identify and use recombinant forms of human enteroviruses as population markers, it has been possible through collaboration with a network of globally distributed collaborating laboratories to investigate the transmission dynamics and network size of individual human enterovirus serotypes, such as echovirus 30 and enterovirus D71. Novel bioinformatic methods to detect and quantify recombination within viral genomes have been more widely applied to investigate its occurrence in the evolution of rhinoviruses and hepatitis B virus.