NERC Industrial CASE PhD studentship: Genetics of tuberculosis susceptibility, progression and diagnosis in a wild animal host



Funding has been secured for a studentship to commence in September 2014. The award will cover UK/EU tuition fees and an annual stipend (in 2013/14 this was £13,726 for full-time students, pro rata for part-time students) for three and a half years. The CASE partner, Animal Health and Veterinary Laboratories Agency, will also provide a £1,000 stipend top up in each year.

Supervisors: Dr Alastair Wilson, College of Life and Environmental Sciences, Centre for Ecology and Conservation, University of Exeter

Professor Robbie McDonald, College of Life and Environmental Sciences, Environment and Sustainability Institute, University of Exeter

Professor Dez Delahay, Animal Health and Veterinary Laboratories Agency, National Wildlife Management Center

Project description: Summary: This project will investigate the genetic basis of variation in tuberculosis infection and its pathology in wild badgers (Meles meles).

Opportunity: Our CASE partners will provide an unparalleled set of ecological, epidemiological and genetic data from a long-running study of badgers at Woodchester Park, Glos. Since 1976, data on >3000 individual animals have been collected, including regular assays of cellular and antibody immune responses and excretion of Mycobacterium bovis, as well as a suite of ecologically relevant phenotypes (e.g. body size, condition, tooth wear, reproduction). Individuals have been sampled longitudinally with multiple recaptures during their lifetimes. Genetic data (microsatellite genotypes) are also available. Together these data provide a rare and timely opportunity to test hypotheses about the genetics of disease susceptibility and progression in wild animals.

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Objectives:

i) Quantify inbreeding and test the hypothesis that inbreeding depression influences expression and fitness consequences of disease traits; 

ii) Use pedigree-based quantitative genetic models to investigate the genetic architecture of TB progression and its relationship to life history.

iii) Estimate natural selection on disease traits (using pedigree-derived measures of fitness).

iv) Combine estimates of selection and genetic variation to predict evolution of disease traits.

Methods: The project is ambitious but “low risk” because all required data are available, though the student will participate in ongoing field data collection (see Training). The first stage of the project will use genetic marker (microsatellite) data to reconstruct the population pedigree structure using maximum likelihood and/or Bayesian methods. Subsequent analyses will employ linear mixed effects models, including quantitative genetic “animal models”. Ideally suited for handling ecological data sets with longitudinal sampling of known individuals, these methods allow simultaneous modelling of genetic and environmental effects on phenotype.

Impact and wider relevance: Though primarily addressing fundamental questions in evolutionary and ecological genetics, the importance of tuberculosis as an animal and public health issue, means that the project will also have wider impacts. For example, it will ask how genetic and ecological factors interact with disease progression, to influence immune response and hence detection of infection by immunodiagnostic testing. Badgers are a valuable model of TB progression since, unlike cattle or humans, there is no clinical intervention after detection and therefore we will have the opportunity to examine how genetic factors affect the likelihood of progression to infectiousness, and morbidity. Thus, results could have a bearing on TB detection and control in cattle and humans as well as badgers.

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The closing date for applications is midnight Sunday 2 February 2014. Interviews are expected to take place in February.

For further information, please visit the apply button below

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