- How protein modifications influence DNA packaging and control of gene expression.
- Environmental influences on gene function, particularly in the early embryo.
- How epigenetic control mechanisms are disrupted in cancer.
Since establishing his research laboratory in Birmingham in the early 1980s, Bryan Turner’s research has focused on how the packaging of DNA by proteins (primarily the histones) can influence gene expression (ie. can turn genes on and off). The primary focus, and achievement so far, has been to show that the histones can be modified at specific amino acid residues by an ever growing variety of enzymes. These enzymes attach and remove chemical moieties such as acetate, methyl or phosphate groups, thereby altering the packaging of DNA in subtle ways and potentially influencing how genes are expressed. Using novel antibodies as molecular probes, the Birmingham group demonstrated that modification (by acetylation) of just a single amino acid residue on one of the four core histones could exert a significant effect of gene expression. It was proposed that individual histone modifications usually operate by acting as receptors for non-histone binding proteins that then, in turn, alter DNA packaging and gene expression (Cell 75, 5-8, 1993). The identification of such binding proteins has confirmed this proposition and the Turner group continues to explore ways in which environmental factors, including chemotherapeutic agents, can alter gene expression through changes in the activities of histone modifying enzymes or binding proteins.
The group uses model systems based primarily of human or mouse cells grown in culture, including embryonic stem cells. Experimental; approaches continue to be based on the use of antibodies specific for particular modified histones, primarily chromatin immunoprecipitation (ChIP) and immunomicroscopy. Novel approaches have been developed that allow the group to work with small numbers of cells and thereby to explore environmentally induced changes in the early embryo or in cell sub-populations isolated by flow cytometry. Sophisticated microscopical approaches provide information on the distribution of histone modifications in single cells, allowing comparison of normal and cancer cells.
The Chromatin and Gene Expression Group comprises Bryan Turner, academic colleagues Laura O'Neill and Karl Nightingale, two postdoctoral Research Fellows, three PhD students and a Clinical Scientist. We work closely with other groups in the IBR, including those headed by Constanze Bonifer, Ferenc Mueller (zebrafish), Jon Frampton and Paul Badenhorst (Drosophila). The groups come together for a weekly joint lab meeting.
His research is currently funded primarily by Cancer Research UK