Molecular mechanisms in atopic skin

Atopic eczema is an itchy inflammatory skin disease which has increased in prevalence over recent decades. It is a complex trait arising from the interaction of multiple genetic and environmental factors, but eczema is highly heritable, demonstrating the importance of genetic predisposition. Multiple risk loci have been identified by genome-wide association studies, but a locus on chromosome 1q21 shows the strongest association. Within this locus, loss-of-function mutations in the FLG gene encoding the skin barrier protein filaggrin are well known to increase risk of atopic disease. Dr Brown has shown that copy number variation within FLG has a dose-dependent effect on eczema risk, and her current work aims to investigate whether related genes show a similar effect. She will also use organotypic skin culture to test the role of candidate genes/transcripts for which functional mechanisms remain to be defined. This work will move towards identifying targets for much-needed therapy development.