I have a long-standing interest in inherited retinal disease and the fundamental processes of phototransduction. One focus of this work is the spectral tuning of visual pigments, with studies of many visual systems including the origin and evolution of trichromacy in primates, the tuning of rod pigments in photon-limited environments, and the molecular basis for the shifts in the peak spectral sensitivity of the shortwave-sensitive pigment class from UV to violet sensitive. We are also investigating the origin of the vertebrate visual system through studies on an ancient vertebrate, the lamprey. These animals possess a full complement of visual pigments for day light or photopic vision but appear to lack pigments for vision in dim light, indicating that the latter evolved in the jawed vertebrate lineage only after it split from the jawless vertebrates about 450 million years ago.

In addition, I have an extensive programme of work directed towards the understanding of mutant gene function in inherited retinal diseases. Major achievements have been the demonstration that a form of dominant cone-rod dystrophy arises from mutations in the gene for retinal guanylyl cyclase (GC) type 1 and we were subsequently able to demonstrate in functional assays using recombinant proteins that the major consequence of mutation was an altered Ca2+ sensitivity of the cyclase. We have also established the functional effects of a mutation in the activator of GC (GCAP1). Animal models with knock-in mutations in retGC1 and GCAP1 have now been developed and are currently being analysed. Another form of cone-rod dystrophy was shown to be caused by mutations in RIMS1 and functional studies on the mechanism of action of mutations in splicing factor genes in the development of retinitis pigmentosa have clarified the disease mechanism. We have also contributed to the molecular analysis of a number of other retinal disorders, most recently, the identification of the mutations in KCNV2 which underlie cone dystrophy with supernormal rod ERG.