‘Epigenetics is a blossoming area of science,’ says Dr Chas Bountra, chief scientist at the Structural Genomics Consortium (SGC) in Oxford. ‘We believe it will deliver new drugs for many common diseases, such as diabetes, cancer, and inflammatory diseases.’
The study of epigenetics tries to understand changes in the action of genes that are inherited but occur without any changes in the DNA sequences.
By understanding these mechanisms of genetic control at a level above the DNA code, researchers believe they can identify factors that lead to many diseases where this control goes awry.
Dr Bountra and the SGC are heavily involved in a new public-private partnership to systematically set about investigating the most important proteins involved in epigenetic control and kick-start the drug-discovery process. They, along with the Departments of Chemistry and Biochemistry, a government laboratory in the USA and pharmaceutical giant GlaxoSmithKline plc (GSK), have just received a £4.1 million investment from the Wellcome Trust over four years.
The funding will allow the partnership to generate chemical compounds or ‘probes’ that bind to 25 different epigenetic control proteins and stop them working. This allows the role of each protein to be understood and whether blocking the target could have a benefit in treating disease. Some of the chemical probes could turn out to be starting points for drug development.
‘To dissect the disease processes in the body, we need good tools, and chemical probes are some of the best,’ explains Dr Bountra.
The chemical probes will be made freely available to anyone in academia, biotech, or pharma. ‘We will provide a complete set of information along with samples of the probes – the three-dimensional structure of the protein target and the probe bound to the target, how to make the probe, and the pharmacological/biochemical activity of the probe – so that everyone has everything they might need to take this work forwards.’
This is a highly unusual step, says Dr Bountra. ‘Intellectual property in pharma has always been closely guarded and knowledge is not shared with other people. Here, GSK is contributing their compounds knowing the results will be made public. This is a major shift in the way pharma works with academia.’
The grant from the Wellcome Trust will be used to recruit 16.5 new employees in Oxford: 10.5 in the Structural Genomics Consortium, five in Chemistry and one in Biochemistry. The SGC will generate the target proteins, determine the structure of the proteins and the bound chemical probes, and all three Oxford groups will be involved in measuring the pharmacological activities of the probes.
The National Institutes of Health Chemical Genomics Center (NCGC) in Bethesda, USA, will screen their set of 270,000 compounds to see if any bind to each of the protein targets, absorbing all the cost themselves (which can be around £0.5 million for each screen: the agreement covers 20 high throughput screens), while GSK will be committing eight chemists at their sites in producing the chemical probes.
‘This will make a big impact in this area of science and drug discovery,’ says Dr Bountra. ‘I feel we will have been successful if we facilitate drug discovery in the area of epigenetics – if biotech and pharma take up these probes and start moving them into the clinic. On the way we will no doubt produce some first rate publications in collaboration with world leaders in epigenetics and drug discovery.’