A major piece of Swansea University-led research is published this week in the top ranked journal The Proceedings of the National Academy of Science of the United States of America, better known as PNAS.
The work, led by Professor Steven Conlan and Dr Deyarina Gonzalez from the University’s College of Medicine, has unravelled a complex molecular mechanism controlling the regulation of genes.
The research, which was funded in part by a Cancer Research UK grant to Professor Conlan, has unravelled a complex biochemical mechanism involving ‘Mediator’ a ‘molecular switchboard’ found in organisms from yeast to man.
Mediator is made up of over 20 proteins that form a very large complex, and is needed to activate or turn on genes. The Swansea team have found one of the ways the ‘switchboard’ can turn off its own function and therefore shutdown the expression of genes.
The research by Professor Conlan and Dr Gonzalez demonstrates how a cascade of molecular events enables Mediator components to dynamically regulate the function of the Mediator complex, and in turn to control large sets of genes.
Put more simply, now the team understands the molecular mechanism controlling the regulation of genes and have found out the very distinctive steps along the pathway, they can focus on whether they can develop a drug that can target or “block” the steps in the mechanism they’ve uncovered, which may ultimately lead to the prevention of further development of cancer in patients.
The work was undertaken in collaboration with groups at the University Medical Centre in Utrecht, The Netherlands, and the European Molecular Biology Laboratory (EMBL) in Germany.
Professor Steve Conlan said:
“We are still in the very early stages of this research, but these findings are an encouraging start and open the way for developing targeted interventions (or drugs) to control gene expression in human diseases.
“In particular, Dr Gonzalez and I, together with our colleague Dr Lewis Francis, who co-lead Reproductive Biology and Gynaecological Oncology research in Swansea’s College of Medicine, will now take these findings and apply them to our research into endometrial (uterine) and ovarian cancer, which will have the ultimate aim of preventing the further development of cancer in patients.”
To view an abstract of the paper, entitled “Suppression of Mediator is regulated by Cdk8-dependent Grr1 turnover of Med3 co-activator”, which is published online in PNAS, visit http://www.pnas.org/content/early/2014/01/29/1307525111.abstract.
For more information on Swansea University’s Reproductive Biology and Gynaecological Oncology research group visit http://www.swansea.ac.uk/medicine/research/a-zofresearchgroups/rbgo/.
