Understanding Rheumatoid Arthritis driven alterations in T-cell epigenetic programing

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.