Research interests

I am currently undertaking a three-year UKRI Innovation Fellowship, jointly funded by the MRC and BBSRC, to investigate the structural basis of antigenic variation among human and avian influenza viruses using a One Health approach. Based at the University of Glasgow, I am a member of both the Institute of Biodiversity, Animal Health and Comparative Medicine and the Institute of Health and Wellbeing. I am also a member of the multidisciplinary Boyd Orr Centre for Population and Ecosystem Health.

Broadly speaking, my interests lie in the relationships between pathogens and their hosts, the evolution of traits such as resistance, virulence and host preference, and how an understanding of these processes can be used to inform disease control and intervention strategies.

Areas of Research

Antigenic evolution of influenza viruses

Factors associated with the emergence and persistence of epidemic avian influenza

Collaboration with the National Health Service

Antimicrobial resistance in the Greater Serengeti Ecosystem


Antigenic evolution of human influenza viruses

I have a keen interest interest in the development of quantitative methods for exploring the antigenic evolution of human influenza viruses humans. Influenza A viruses are characterised by rapid antigenic drift: amino acid substitutions cause biophysical structural changes to B-cell epitopes that facilitate escape from pre-existing immunity in the human population. Consequently, seasonal influenza continues to impose a major burden on human health. Accurate quantification of the antigenic impact of specific amino acid substitutions is a prerequisite for predicting the fitness and evolutionary outcome of variant viruses.

My PhD was based at the University of Glasgow under the supervision of Richard Reeve, Dan Haydon, and John McCauley (The Francis Crick Institute) and focused on the antigenic drift of seasonal influenza viruses. Viruses of the influenza A subtypes A(H1N1) and A(H3N2) circulate globally in the human population causing seasonal epidemics and requiring a global surveillance program responsible for on-going antigenic characterisation and vaccine composition recommendations. The identification of emerging antigenic variants among circulating influenza viruses is critical to the vaccine selection process, with vaccine effectiveness maximised when constituents are antigenically similar to circulating viruses.

hischematic

The antigenic data we use often comes from the haemagglutination inhibition assay. It measures the extent to which antibodies recognise and bind influenza virus preventing the agglutination of red blood cells.

Analysing antigenic and genetic data generated at the The Worldwide Influenza Centre at the Francis Crick Institute (formerly the WHO Collaborating Centre for Reference and Research on Influenza at the National Institute for Medical Research), I have focused on the application of statistical models to these data in order to to identify molecular determinants of antigenic phenotype, quantify the antigenic impact of specific amino acid substitutions, and to make predictions of antigenicity from sequence. To find out more about my PhD work, find my thesis online.

Read more: Identification of low- and high-impact hemagglutinin amino acid substitutions that drive antigenic drift of influenza A(H1N1) viruses


Antigenic variation among RNA viruses of livestock and poultry

Working in collaboration with researchers at the Pirbright Institute and the ARC-Onderstepoort Veterinary Institute (OVI), Richard Reeve and I are involved in efforts to determine the genetic basis of antigenic variation among multiple serotypes of foot-and-mouth disease virus (FMDV). Globally, FMDV is one of the most economically important livestock diseases and is still widely distributed. Novel genetic and antigenic variants continue to emerge within each of the six recently observed serotypes of the virus, which has confounded attempts to develop vaccines that protect against a broad range viruses, even within serotypes. Such broad-range protection is one of the major goals underpinning current research in FMDV vaccine development, making it vitally important to identify those areas of the capsid that are targets for protective immunity.

Read more: Tracking the antigenic evolution of foot-and-mouth disease virus

More recently, Richard and I have applied these methods to avian influenza A(H9N2) collaborating with Thomas Peacock and Munir Iqbal at the Pirbright Institute. A(H9N2) viruses are a major cause of poultry production losses across Asia, vaccination is widespread however the emergence of antigenic variants is a significant factor compromising their efficacy. Most knowledge of the antigenicity of A(H9N2) viruses is derived from the results on monoclonal antibody escape studies in mice. Through this work we hope to reveal more about the antigenic evolution of natural isolates and the genetic differences among A(H9N2) viruses that contribute to loss of vaccine effectiveness.

Richard and I have also been working with Vinny Davies and Dirk Husmeier who are based within the School of Mathematics and Statistics in Glasgow.  Vinny recently completed his PhD in Glasgow and has interests in the application of Markov chain Monte Carlo methods to biological data and the development of improved Bayesian methods for variable selection. Identifying the genetic changes involved in antigenic evolution usually requires distinguishing between large numbers of, often highly correlated, variables. We have successfully applied mixed-effects models using slab and spike priors to FMDV and influenza datasets detecting antigenic residues. To read about this work in detail take a look at Vinny’s thesis.

Read more: Selecting random effect components in a sparse hierarchical Bayesian model for identifying antigenic variability

Sparse Bayesian variable selection for the identification of antigenic variability in the foot-and-mouth disease virus