First degree in genetics (Cambridge); DPhil on early gene mapping studies using somatic cell hybrids, with Walter Bodmer (Oxford); Beit Memorial Fellow, MRC Mammalian Genome Unit, Edinburgh; eventually rose through the ranks at MRC Human Genetics Unit, Edinburgh from postdoctoral fellow to group leader and Section Head. Honorary Professor University of Edinburgh, FRS, FRSE, FMedSci. Howard Hughes International Research Scholar 1993-1998. Member of UK Human Genetics Commission 2000-2005. EMBO member 2003. Fellow of the Royal Society 2007.
Human geneticist (non-clinical) working on developmental eye anomalies such as aniridia and anophthalmia/microphthalmia. Interested in what detailed analysis of the human phenotypes in individuals with known mutations can tell us about the biological role of the genes involved. Ultimately most human developmental genes need to be explored in model systems and we are currently studying the roles of PAX6 and SOX2 in humans, the mouse and zebrafish. A major area of endeavour since the early 1990s is to understand the mechanisms of long-range regulation of gene expression. Transcription factors like PAX6 and SOX2 show complex spatiotemporal and quantitative control of expression, requiring a large number of strongly sequence-conserved cis-regulatory elements, found upstream, downstream and within the gene. Such regulatory regions can stretch more than a megabase either side of the gene. We are aiming to understand the spatial and functional organisation of these interacting elements (which often function as enhancers in reporter transgenic assays), additively recapitulating the sum of the total gene expression pattern. Expression-associated patterns of open chromatin suggest dynamic genomic organisation. Another emerging interest is in the mechanisms underlying disease with non-Mendelian segregation patterns. We are exploring how environmental factors effect phenotype modification.
