April 2013

School Announces Research Opportunities in Rheumatology

Sat, 20 April 13 09:00

The School is pleased to announce two research opportunities in Rheumatology within the team of the incoming Arthritis Ireland/UCD Chair of Rheumatology, Prof Gerry Wilson at the UCD School of Medicine & Medical Science.

Prof Wilson joins the School from the University of Sheffield Medical School where he led a EULAR Centre of Excellence for Rheumatology. Prof Wilson will establish a new rheumatology research group at the UCD Conway Institute and is seeking to make two initial appointments.

Applications are now invited for a Post Doctoral Research Fellow and a PhD Research Studentship.

About Rheumatoid Arthritis

Rheumatoid arthritis (RA) is the commonest chronic inflammatory joint disease and is characterised by synovial inflammation which, if uncontrolled, leads to cartilage and bone damage. The clinical course of RA is heterogeneous with wide variation in severity as assessed by parameters such as disease activity, functional status, and x-ray damage.

The identification of biomarkers of poorer outcome should, in combination with established biomarkers, facilitate patient stratification and improved therapeutic targeting.

Major progress in our understanding of the pathogenesis of RA has been made over the past few years with the identification of environmental risk modifying factors such as alcohol consumption and smoking whilst advances in genetics has led to the discovery of >45 susceptibility genes mostly encode immune-related proteins.

(1) Post Doctoral Fellow

This research project will use high throughput genetic, transcriptomic, proteomic and immunological techniques to identify biomarkers associated with poorer outcome using samples from 1,007 RA patients (1-3). This data would guide therapeutic targeting with more aggressive regimes resulting in less joint damage and improved quality of life of RA patients with unfavourable biomarker profiles.

Previous experience in genetic or genomic research is essential and basic statistical techniques an advantage.

References

  1. Teare, D.M., Knevel, R., Morgan, M.D., Kleszcz, A., Emery, P., Moore, D.J., Conaghan, P.G., Huizinga, T., Morgan, A.W., van der Helm-van Mil, A., et al. 2013. Allele dose association of the C5orf30 rs26232 variant with joint damage in rheumatoid arthritis. Arthritis Rheum.
  2. Maxwell, J.R., Marinou, I., Kuet, K.P., Orozco, G., Moore, D.J., Barton, A., Worthington, J., and Wilson, A.G. 2012. Rheumatoid Arthritis-associated Polymorphisms at 6q23 Are Associated with Radiological Damage in Autoantibody-positive RA. J Rheumatol 39:1781-1785.
  3. Marinou, I., Walters, K., Winfield, J., Bax, D.E., and Wilson, A.G. 2010. A gain of function polymorphism in the interleukin 6 receptor influences RA susceptibility. Ann Rheum Dis 69:1191-1194. Applications

Application

This post doctoral research fellowship opportunity is funded by the School for a period of three years at an appropriate point on the UCD Post Doctoral Fellows salary scale. Interested parties should submit a letter of application and their CV by email to Prof Wilson (aDOTgDOTwilson@sheffield.ac.uk)(Replace DOT with '.').

(1) PhD Research Studentship

The role of epigenetics in the pathogenesis and treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is the commonest chronic inflammatory joint disease and has a prevalence of 1%. It is characterised by synovial inflammation which, if uncontrolled, leads to cartilage and bone damage. Major progress in our understanding of the pathogenesis of RA has been made over the past few years with the identification of environmental risk modifying factors such as alcohol consumption and smoking whilst advances in genetics has led to the discovery of >45 susceptibility genes mostly encode immune-related proteins.

Recent evidence implicates epigenetic mechanisms in the pathogenesis of RA and there is increasing interest in therapeutically targeting the epigenome, as this is effective in animal models of RA (1, 2). This project will determine the epigenetic profiles of peripheral blood leucocytes and synovial cells in RA and determine if clinical responses to commonly used treatments, such as methotrexate and TNF inhibitors, are associated with resetting of the epigenetic signature. This information will lead to a better understanding of the role of epigenetics in the pathogenesis of RA and may result in the identification of novel therapeutic targets.

The project will involve cell culture, DNA and RNA purification, DNA sequencing, gene arrays and bioinformatics.

References

  1. Karouzakis, E., Gay, R.E., Michel, B.A., Gay, S., and Neidhart, M. 2009. DNA hypomethylation in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 60:3613-3622.
  2. Nile, C.J., Read, R.C., Akil, M., Duff, G.W., and Wilson, A.G. 2008. Methylation status of a single CpG site in the IL6 promoter is related to IL6 messenger RNA levels and rheumatoid arthritis. Arthritis Rheum 58:2686-2693.

Application

This opportunity is a fully funded PhD position with doctoral registration fees and a student stipend funded by the School for a period of four years subject to satisfactory progression. Interested applications should apply by email to Prof Wilson (aDOTgDOTwilson@sheffield.ac.uk)(replace DOT with'.')