Nobel prize for medicine goes to discovery of how cells sense oxygen

By | October 9, 2019
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Niklas Elmehed

The Nobel prize in physiology or medicine has been jointly awarded to William Kaelin of Harvard University, Peter Ratcliffe of Oxford University and Gregg Semenza of Johns Hopkins University, for their discovery of how cells sense and adapt to oxygen availability.

Between them, the three discovered the molecular switch that controls how our cells respond to varying levels of oxygen in the surroundings. This not only helps explain how the body responds to change, but has implications for treating a range of disorders, from anaemia to heart attack and cancer.

Cells need oxygen to survive, but they don’t have a steady supply – levels vary at different altitudes, but also during exercise. Oxygen supply is also disrupted when the blood supply is cut off in diseases like cancer and stroke.

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To understand how cells respond to these variations, Gregg Semenza studied the gene for erythropoietin (EPO), a hormone that produces more red blood cells when oxygen levels are running low.

Semenza found that the increase in EPO was due to a specific region of the gene. He identified two proteins that essentially control how the gene works. One of these was found to respond to oxygen levels – it is present when levels are low, but disappears when there is plenty of oxygen around.

Ratcliffe and Kaelins identified another protein, called VHL, that is responsible for destroying that protein when oxygen levels are high. Together, the work of the three prizewinners reveals a molecular switch for responding to oxygen levels.

Since then, at least 300 genes have been found to be regulated by the original protein identified by Semenza. These genes have important roles in health – some control how new blood vessels are formed, and others influence how cells break down glucose, for example. The genes are known to be important in the development of embryos and the functioning of the immune system.

The molecular switch is also important in understanding and treating disorders like anaemia, which results in low oxygen levels, and diseases like stroke, heart attack and cancer, which can also shut off the blood oxygen supply to cells.

The work by Semenza, Ratcliffe and Kaelins is already changing the way medicine is practised, say the Nobel prize committee – a drug based on their work is already being used to treat some cancers.

That’s because cancer tumours have been found to have increased levels of the protein discovered by Semenza in response to low oxygen levels. Drugs that inhibit the protein can help kill the tumour.

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