Dermatology and Genetic Medicine: A multidisciplinary research initiative aimed at translating basic science discoveries in genetic skin disease into clinical application. (360G-Wellcome-098439_Z_12_Z)

Dermatology is an under-resourced area of research, however, the University of Dundee has established a critical mass of internationally competitive researchers in genetic skin disease and cutaneous therapy development. This award will strengthen this multidisciplinary research centre and catalyze further clinically applicable research at the interface of genetics, dermatology and drug discovery. Specifically, a large collection of diverse monogenic disorders accumulated through a UK genoderma tology network will be analysed using whole exome sequencing approaches, informed by transcriptome analysis. Targeted sequence capture and next-generation sequencing of loci identified by genomewide association studies will discover new causative variants in eczema, in addition to streamlining analysis of the large, repetitive filaggrin gene. Our previous genetics work has identified a number of new therapy targets tractable by small molecule approaches, which will extended here. A profession ally-managed biotech-style cutaneous drug discovery portfolio will be developed (3 projects already initiated) and extended to run 15 high-throughput screens, supported by hit validation and early hit-to-lead chemistry, with the aim of taking at least 2 dermatology targets through to pharmaceutical partnering. Animal and cell-culture platforms for assessing cutaneous drug/siRNA delivery/efficacy will be established. This award will also strengthen our capacity for patient outreach and training of new investigators.