Professor Chris Schofield
A recent focus of his work has been in developing a better chemical understanding of genetics, particularly to uncover how information can be transferred between generations without changes in DNA sequences. But another project, that has utilised basic chemistry to identify how humans sense changes in oxygen levels, has made a big splash in the pharmaceutical industry.
Working with the Ratcliffe-Pugh group in the Nuffield Department of Clinical Medicine, Chris and his team set out to understand the chemistry behind how humans sense, and respond, to the presence of oxygen. In the human body, oxygen-regulated proteins affect how cells respond to differing levels of the gas. When there is a shortage, the proteins activate a host of genes involved in the adaptation of cells to the lowered oxygen levels. The result is that the body produces more red blood cells and blood vessels to cope with the lower oxygen concentration.
Chris and his team discovered a family of enzymes that sense oxygen in order to regulate the activity of these proteins - which are oddly enough actually closely related to the ones responsible for the production of penicillin. Since then, Chris’s group have been working hard to characterize them so that they can develop medications to artificially recreate the body’s reaction to a shortage or excess of oxygen.
Artificially boosting the production of red blood cells and growth of vessels, by blocking the sensing enzymes, alleviates the symptoms of conditions like anaemia. What is more, activating the enzymes can suppress blood vessel growth, which helps in the treatment of cancer. Together with pharmaceutical companies, the University’s spin-out company ReOx is now helping to develop new anaemia treatments, and several compounds are in clinical trials.
Indeed, so impressive are Chris’s achievements that they have been recognised by awards such as the Royal Society of Chemistry’s Jeremy Knowles Award in 2011. But even more reward is that the basic science involved in the work has inspired labs around the world, and that has led to the discovery of a whole family of enzymes that modify DNA and its associated proteins. It turns out that mutations to genes caused by some of these enzymes are linked to cancer, mental degradation and cleft pallet - a finding which Chris hopes to capitalise on in the future.