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. This has entailed use and development of a variety of molecular biology laboratory methods, and a wide range of genetic and bioinformatic analysis techniques that have been widely applied in a variety of virus groups.
Virus / host interactions. In the viral pathogenesis field, my recent research has been focussed on the characterisation of RNA secondary structure in viruses, and its effect on virus evolution. 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. The evolutionary and functional basis for the pervasive suppression of CpG and UpA dinucleotides in RNA viruses is a second, related area of research. The discovery that viruses with high frequencies of CpG/UpA are recognised and their replication suppressed 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 71.
Clinical Virology Research. I am closely involved in an active ongoing programme of research in clinical virology ranging from basic science molecular epidemiology, evolutionary and pathogenicity studies through to investigations of the impact and newly discovered and emerging viruses in human health. I am a member of a consortium developing and evaluating the efficacy and potential future clinical application of high-throughput sequencing methods (Illumina / Nanopore) in viral diagnostic and epidemiological surveillance. , and the development of diagnostics for patient screening and monitoring.
Virus Classification. In a more applied area, I initiated proposals for classification of HCV into genotypes and subtypes and developed a nomenclature system now adopted worldwide. This initiative brought clarity and a framework for subsequent clinical investigations of genotype-associated differences in pathogenesis and treatment response. Similar genetic-based approaches for classification of human rhinoviruses and hepatitis E virus have been implemented. As a member of the ICTV Executive committee, I am involved in broader advancement of the use of genetic relationships as the primary means for virus classification and a major re-structuring of how virus classification information is provided to the wider virological community.
Collectively, these investigations fit into a broader theme of research work in the nature of evolutionary process in RNA viruses, how it differs from that of their mammalian hosts, how this and recombination shapes their molecular epidemiology and clinical manifestations.