The aim of my research is to understand the molecular basis of inherited retinal degeneration, in particular Retinitis Pigmentosa (RP). This is being achieved through molecular investigations of disease models in the laboratory and clinically based studies of the genotypes and phenotypes of patients with inherited retinal degeneration (in collaboration with clinical colleagues, Miss Giuliana Silvestri and Mr Colin Willoughby). Both approaches provide important information, such as lists of genes with altered expression during retinal degeneration or the specific mutations responsible for patients’ conditions. Whilst this is very useful, the integration of this information and the vast amounts of publicly available data using bioinformatic tools will reveal additional insights into the normal function of the retina and pathological conditions. To this end, my group is using existing tools to investigate global gene expression profiles (eg VectorXpression, GenMAPP and applying datamining techniques to study genotype:phenotype relationships within RP. As we move towards the practical possibility of using systems biology to model aspects of retinal function, we are developing closer links with bioinformaticians (SBR(N)ET).
Standard and quantitative RT-PCR (on a LightCycler platform)
cDNA microarray analysis
Light and confocal microscopy
Recent technological advances have made it possible to interrogate multiple sequences from many genes simultaneously. In addition to discovering the primary causal mutation it is now becoming feasible to genotype all the loci known to be involved in inherited retinal dystrophy and therefore investigate the modifying effects that sequence variants at other loci may be exerting. We have therefore designed a custom re-sequencing genechip which will be available in summer 2006. This carries almost 30,000bp, comprising regions containing multiple known mutations (‘hot-spots’) in genes known to cause ARRP, ADRP, XLRP and LCA.
The organisation of the Centre for Vision Science promotes collaboration and I am involved in several projects which include the analysis of splicing in the retina, the genetic basis of AMD and the effects of diabetes on gene expression (with Dr Tim Curtis).