Dr David Boam (BSc, PhD) - research
Transcriptional control of gene expression
Eukaryotic gene expression is regulated at the transcription level by flanking regions of DNA which act as binding sites for sequence-specific transcription factors. Some of these factors are proto-oncogene products or nuclear receptors which activate transcription after directly binding a variety of ligands such as steroids, morphogens, prostaglandins and drugs used to treat type II diabetes and obesity.
Our research is focused in 2 areas - how gene transcription is regulated during the cell cycle, and the molecular biology of a novel nuclear hormone receptor, the PPAR which plays an important role in the genetic regulation of lipid metabolism and type II diabetes
Regulation of cyclin gene transcription
Cyclins are pivotal in the regulation of cell proliferation and their genes are transcribed in a cell cycle dependent manner. The cyclin B1 gene is expressed just prior to mitosis by a mechanism, which is poorly understood. We are studying this using a novel in vitro transcription assay which can mimic mitosis by addition of recombinant cyclin, by isolating transcription factors which confer cell cycle-specific regulation and by real-time imaging of cells micro-injected which cyclin promoter-luciferase reporter genes.
Molecular biology of the peroxisome proliferator-activated receptor (PPAR)
PPARs are identified members of the nuclear hormone receptor family, which includes the oestrogen, thyroid hormone and retinoic acid receptors. They play an important role in regulation of genes controlling lipid metabolism and adipocyte differentiation as well as being targets for insulin sensitiser and hypolipidemic drugs. We are studying the role of the PPAR in the regulation of pancreatic islet-specific genes by fatty acids and insulin sensitiser drugs - an important link between obesity and diabetes. The PPAR also directly interacts with other transcription factors, thus permitting crosstalk between different signal transduction pathways. We are investigating this phenomenon with the aim of using it to develop novel agents, which selectively modulate lipid metabolism and cell proliferation.