Epigenetic regulation of experimental arthritis

Recent successes of therapeutic intervention of chronic inflammatory diseases using epigenetic modifiers such as histone deacetylase inhibitors and inhibitors of DNA methylation suggest that epigenetic reprogramming plays a role in the aetiology of these diseases. However, the disease mechanisms driving epigenetic modulation in chronic inflammation are poorly understood. Therefore, identifying disease specific epigenetic marks in the genome would provide excellent clues to disease pathways as well as serve as potential therapeutic targets. We are focusing on an experimental form of rheumatoid arthritis and aim to identify such arthritis regulating epigenetic modifications in the rat genome the genes that are affected by epigenetic modifications and the differential expression of genes as a result. Methods: 1- differential gene expression: The student will be using qRT-PCR to quantify altered gene expression in healthy and arthritic rat cells treated with epigenetic modifiers. Flowcytometry and ELISA will be used to identify cellular characteristics of the cells involved in disease development. 2 -differential DNA methylation: The student will use immune precipitation to enrich for epigenetic regulated genomic regions. qRT-PCR and bisulphite sequencing will be used to assess the levels of epigenetic modification of specific genomic regions.