Professor Bernard J Morley

My research is directed towards understanding the aetiology of the disease systemic lupus erythematosus (SLE) via a genetic approach.  This has been based on a model system, which manifests a disease very similar to human lupus with anti single-stranded and double-stranded DNA antibodies, anti-nuclear antibodies and a severe nephritis causing mortality by six to nine months of age.  The model also has an accelerating factor on its Y chromosome, the Yaa gene.  The use of this model has enabled my research group to perform extensive linkage analysis and resulted in the identification of six loci with associated phenotypes, which underlie the susceptibility to lupus in the BXSB strain.  Of these loci, four (Bxs1-4) are located on chromosome 1 with Bxs5 a potential suppressor locus on chromosome 3 and Bxs6 linked to the production of gp70 alone, on chromosome 13 (publications 25, 27, 29, 32).  The linkage studies have enabled us to align different aspects of phenotype with these loci such that Bxs3 is associated with high autoantibody production but less so with nephritis while Bxs1 has been liked with nephritis seemingly in the absence of autoantibody production.  

We have taken advantage of the ability to perform directed breeding in a model system to produce a series of overlapping congenic lines for chromosome 1 and individual lines for chromosome 3 and chromosome 13.  These contain large intervals and therefore as a complementary approach we have used the analysis of differential expression to identify potential disease susceptibility loci within the congenic intervals using the Affymetrix microarray system. 

The long-term strategy is to understand the aetiology of SLE and to identify the genes which underlie susceptibility to this disease. We then aim to use this information to identify disease mechanisms in a clinical context and eventually to develop novel therapeutic targets.