Research
Update! I have just joined the Nuffield Department of Clinical Medicine at Oxford University, as "Leadership Fellow in Genomic Medicine". A large part of my new activities will involve the Modernising Medical Microbiology project, as part of which I will be advertising a post-doc and graduate student position. Until I update the website, visit the MMM homepage or read on for my research interests to date.
Until December I was a Post-doctoral Research Scholar in Molly Przeworski's lab at the University of Chicago Department of Human Genetics. My research interests centre on the application of population genetics tools to solving problems in human infectious diseases. Another major interest of mine is detecting the signature of natural selection within populations. My software omegaMap is designed to address that problem in recombining populations, and is available to download from this site.
For more information on my research interests please see
- omegaMap: Detecting natural selection in genes
- Campylobacter source attribution and evolution
- Meningococcal meningitis
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Links to collaborators' websites
- Publications
- Contact me
omegaMap: Detecting natural selection in genes
As part of my research into the evolution of the interaction of the immune system with pathogen antibodies, I have developed a new method for detecting natural selection in gene sequences in the presence of recombination. The method uses the codon model of Nielsen and Yang (1998) to estimate variation in the dN/dS ratio (the ratio of non-synonymous to synonymous mutation) along a gene. Previous methods have not allowed for recombination, which occurs frequently not just in genes from bacteria such as Campylobacter and Neisseria meningitidis, but also viruses such as HIV, protozoans such as Plasmodium and eukaryotes including humans. When recombination is not accounted for it can elevate the false positive rate for detecting sites under positive selection.omegaMap is a program that implements the method, and is freely available from here. The key publication is
Wilson, D. J. and G. McVean
Estimating diversifying selection and functional constraint in the presence of
recombination. (Abstract)
Submitted to Genetics.
Campylobacter source attribution and evolution
As a Research Associate in Genetics at Lancaster University Department of Maths and Statistics my research was concerned with exploiting the information contained in patterns of DNA sequence variation to learn about the spatial epidemiology of Campylobacter in humans, a common bacterial infection that causes gastroenteritis. I worked with Paul Fearnhead, Edith Gabriel and Peter Diggle in Lancaster, in collaboration with groups at Liverpool Vet School and Manchester Royal Infirmary.
The idea is that genetic variation in pathogen populations contains an (albeit corrupted) record of the evolutionary history of the species. Evolutionary models are applied to DNA sequence data (notably MLST in the case of bacterial pathogens) in order to extract that historical information, which can then be used to inform epidemiological studies. For Campylobacter we are specifically interested in modelling the spatial and temporal epidemiology of cases in the North of England over a period of a decade.
Meningococcal meningitis
Previously I was based at the Peter Medawar Building for Pathogen Research in Oxford, where I wrote my D.Phil. thesis on the population genetics of meningococcal meningitis. In Oxford I was a member of the Mathematical Genetics and Bioinformatics group, and jointly supervised by Gil McVean and Martin Maiden.
The title of my D.Phil. thesis was 'Multi-locus sequence analysis of the pathogen Neisseria meningitidis'. N. meningitidis is the bacterium that causes meningococcal disease (meningitis and septicaemia) in humans at a rate of about 1 case per 20,000 people per year in England (see the Meningitis Research Foundation). Its asympotmatic carriage rate is higher - around 10% in Europe and the US. Virulence is not thought to be important in the spread and persistence of N. meningitidis, so recent research has concentrated more closely on studying the populations of meningococci carried asymptomatically by one in ten of us.
Our research showed that contrary to simpler ideas of the evolution of bacterial pathogens, natural selection is an important force in shaping populations of carried meningococci. The heterogeneity of different strains, or clonal complexes, of meningococci, the apparent stability of these clonal complexes over time, and the different characteristics of the clonal complexes (including genetic composition and propensity to cause disease) cannot be explained by neutral models of meningococcal evolution. Some of the key publications I have been involved in are
Jolley, K. A., D. J. Wilson, P. Kriz, G. McVean and M. C. J. Maiden (2005)
The influence of mutation, recombination, population history and selection on
patterns of genetic diversity in Neisseria meningitidis.
Molecular Biology and Evolution 22: 562-569. (pdf)
Yazdankhah, S. P., P. Kriz, G. Tzanakaki, J. Kremastinou, J. Kalmusova, M.
Musilek, T. Alvedstad, K. A. Jolley, D. J. Wilson, N. D. McCarthy, D. A.
Caugant and M. C. J. Maiden (2004)
Distribution of Serogroups and Genotypes among Disease-Associated and Carried
Isolates of Neisseria meningitidis from the Czech Republic, Greece, and
Norway.
Journal of Clinical Microbiology 42: 5146-5153. (pdf)
Claus, H., M. C. J. Maiden, D. J. Wilson, N. D. McCarthy, K. A. Jolley, R.
Urwin, F. Hessler, M. Frosch and U. Vogel (2005)
Genetic analysis of meningococci carried by children and young adults.
Journal of Infectious Diseases 191: 1263-1271. (pdf)
