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MBiochem final year student

Understanding the role of regulatory elements in driving allelic associations with differences in gene expression in human leukocytes for different cellular contexts

rebecca.jpegInappropriate immune activity and associated inflammation are involved in the pathogenesis of a broad range of common diseases, including IBS, atherosclerosis, rheumatoid arthritis and cancer. eQTLs are regions of the genome containing DNA sequence variants that influence the expression of one or more genes. Previous work by the group has shown that there is an allelic association with gene expression specific to different human leukocyte cell types and states of cellular activation. The functional alleles are associated with differences in gene expression, and act by modulation of gene regulation through regulatory elements involving enhancers, promoters and similar genomic regions.

I am undertaking an 18-week project searching for evidence of overlap of regulatory variants that act in particular leukocyte contexts on eQTL mapping (identified previously) and regulatory elements specific to those contexts revealed by ATAC-seq mapping. This technique provides accurate, genome-scale mapping of chromatin accessibility, thus giving an indication of the activity of different regions of the genome in the leukocytes cultured in different contexts. It is hoped that evidence provided could be used to identify cellular pathways and molecules that were not previously thought to be involved in disease processes and that are potential therapeutic targets.