Research Interests: Chromatin, Gene regulation, Imprinting, GPCRs, Functional Genomics, Proteomics.
Genes that encode non-histone chromo-somal proteins: The modulation of chro-matin domains is the first step in the regulation of gene expression in eukary-otes. Yet the assembly of DNA and proteins into active and inactive chromatin, and into chromosomes, is a process about which we know very little. We have isolated mutations in Drosophila that actually alter both chromosome and chromatin structure and consequently also regulate gene expression and developmental switches. Many of these genes are conserved in vertebrates. We are focussing our current work on the molecular analyses of these genes and their products including DNA sequence analysis, cellular and developmental expression of theprotein products, dissecting the hierarchy of gene action and protein interactions in the assembly of chromatin in vivo.
Functional Genomics of Human Proteins: We have created a system, called InsectSelect™, that allows us to express human proteins in transformed, stable insect cell-lines. The human proteins function normally in this ex vivo setting. We have been able to express over 6 different genes/proteins in a single transformed cell-line. This allows us to re-constitute virtually any part of the human proteome, i.e. any human pathway and/or complex, and study it away from other factors. While, this technology is applicable to a wide variety of functional genomic studies we are particularly interested in Pharmacogenomics, which is the study of the effects of individual genetic variation on patient response to drug therapy. For these studies we have expressed human G-protein coupled receptors and the human G-proteins to which they couple and engineered these to signal to insect effector molecules (signal transduction pathways). We are studying polymorphisms in the human population (SNPs) and correlating these with drug efficacy.