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Understanding Rheumatoid Arthritis driven alterations in T-cell epigenetic programing

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  • Full or part time
    Dr Ponchel
  • Application Deadline
    Applications accepted all year round

Project Description

Dr Ponchel group is leading an analysis of genome wide methylation of T-cells subsets between health and Rheumatoid arthritis (RA) as part of a European research consortium. T-cells are deeply involved in RA pathogenesis at the genetic levels with many susceptibility genes lying in T-cell response pathways (1), at the cellular levels with the disruption of normal T-cell differentiation (2) homeostasis (3,4) and immune regulation (5). At the molecular levels, several significant signalling defects were identified (6).
This project will investigate how to approach bioinformatics methylation data with respect to the analysis of methylation itself which remains a challenge on its own and how to link it with genetics and expression data.
Additional experiments will be carried out to confirm differential methylation using direct bisulphite DNA sequencing of candidate loci in a view of developing progression biomarkers from at risk individuals to fully diagnosed RA patients as well as with respect to predicting therapeutic response.
The biological consequences of such differences will also be investigated using molecular techniques and in vitro cell culture where appropriate.

Funding Notes

Leeds is offering Research Scholarships to home/EU/international students.
Applicants are encouraged to contact supervisors to discuss the specifics of the project and the availability of different scholarship schemes.
Applications must be completed online to obtain a student number.
Offers are made to the most able students as soon as possible.
Applications will also be considered from Self-Funded Students. If you have the correct qualifications and access to your own funding, either from your home country or your own finances, your application will be considered for this project. However, tuition and bench fees will be payable for this project.

References

1.Eyre S, et al. High density genetic mapping identifies new susceptibility loci for RA. Nat Genetics. 2012, 44: 1336-1340.
2.Ponchel F, . et al. Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis. Blood. 2002. 100, 4550-56
3.Ponchel F,. et al. IL-7 deficiency and prolonged therapy-induced lymphopenia in rheumatoid arthritis. Arthiris Research & Therapy. 2005, 7: 80-92.
4.SM Churchman, et al , F Ponchel. Modulation of peripheral T-cell function by interleukin-7 in rheumatoid arthritis. Arthiris Research & Therapy, 2015, 16: 511-520.
5.CA Lawson, F Ponchel et al,. Early rheumatoid arthritis is associated with a deficit in the CD4+CD25high regulatory T cell population in peripheral blood. Rheumatology 2006 45: 1210-17.
6.Ponchel F, et al. CD4+ T-cell subsets in Rheumatoid Arthritis. Int J Clinical Rheumatology, 2012 : 7. 37-53.

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