Determining the role of the IL2 pathway in susceptibility to juvenile idiopathic arthritis

The Centre for Musculoskeletal Research invites applications for a 3-year Arthritis Research UK funded PhD due to commence October 2014. The studentship covers UK/EU tuition fees, research expenses and annual tax-free stipend starting at £14, 212. The studentship is open to UK/EU nationals only due to the nature of the award.

Juvenile idiopathic arthritis (JIA) is an umbrella term for all chronic childhood arthropathies and can be classified into seven subtypes. A recent, landmark genetic study in a large cohort of three subtypes of JIA led by the Arthritis Research UK group here in Manchester, recently identified 17 loci that reached genome-wide significance(1). One consistent finding has been the association of SNPs within three genes in the IL2 pathway. The IL2 signalling pathway is essential for regulation of immune responses. Impairment of this pathway has been shown to affect tolerance of self-antigen, knockout mice deficient for any of these genes develop severe autoimmunity and early death. These genes have also been associated with multiple other autoimmune diseases.

This PhD project will combine statistical, bioinformatics and laboratory techniques aimed at characterising the role of the IL2 signalling genes in conferring susceptibility to JIA and its subtypes. To determine whether SNPs in the IL2 pathway are important in all JIA or specific subtypes, additional JIA cases will be genotyped. The data will then be combined with previously generated GWAS and Immunochip genetic data.

The study will therefore seek to determine:

- Whether the IL2 pathway genes are associated across all subtypes of JIA.

- Whether genes in the IL2 pathway are important in JIA susceptibility and if prioritizing variants in this pathway yields any additional putative disease associations for JIA and its subtypes.

- The cumulative risk of variants in all IL2 pathway genes.

Bioinformatic investigations will be performed to prioritise potential functional variants in the design of future functional experiments. Extensive training in genotyping, statistical/epistasis analysis, FACS, eQTL analysis, ChIP and RNA sequencing will be provided.

The successful candidate will be based in the Arthritis Research UK Centre of Genetics and Genomics, which holds an international reputation in the study of genetic risk factors for rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis and treatment response.

Candidates are expected to hold (or be due to obtain) a minimum upper-second (or equivalent) undergraduate degree in a relevant biomedical/social science/statistics/mathematics area. A Masters qualification would be an advantage.

Please direct applications in the following format to Sumita Chopra ([Email Address Removed]):

- Academic CV
- Official academic transcripts
- Contact details for two academic referees
- A personal statement (750 words maximum) outlining your suitability for the study, what you hope to achieve from the PhD and your research experience to date.

Any enquiries relating to the project and/or suitability should be directed to Dr Joanna Cobb ([Email Address Removed]). Deadline for applications: 30 April 2014

http://www.medicine.manchester.ac.uk/staff/155190
http://www.inflammation-repair.manchester.ac.uk/Musculoskeletal
http://www.mhs.manchester.ac.uk/postgraduate/

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