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How cells sense oxygen wins Nobel prize

Three scientists who discovered how cells sense and adapt to oxygen levels have won the 2019 Nobel Prize for physiology or medicine.

The award was shared by Britain’s Sir Peter Ratcliffe and two Americans, William Kaelin and Gregg Semenza.

Their findings affect our day-to-day life from exercise, to being at high altitudes to our early development in the womb.

Their work is leading to new treatments for anaemia and even cancer.

The Swedish Academy said: “The fundamental importance of oxygen has been understood for centuries, but how cells adapt to changes in levels of oxygen has long been unknown.”

Sir Peter Ratcliffe is based at the Francis Crick Institute and the University of Oxford in the UK, William Kaelin at Harvard in the US and Gregg Semenza at Johns Hopkins University in the US.

Oxygen

Oxygen is in every breath we take, our bodies are completely dependent on it for converting food into usable energy.

But oxygen levels vary in the body, particularly during exercise or at high altitude, or after a cut or wound disrupts the blood supply.

When oxygen levels drop, cells are forced to rapidly adapt their metabolism.

The oxygen-sensing ability of the body can trigger the production of new red blood cells or the construction of new blood vessels.

It also has a role in the immune system and the earliest stages of our development inside the womb.

How does the body senses oxygen?

The story of how our bodies respond to oxygen levels was worked out back to front.

It was shown that a hormone, called erythropoietin or EPO – went up as oxygen levels went down, but why?

Piece-by-piece, the trio solved the puzzle.

First they showed that a cluster of proteins called hypoxia-inducible factor – or HIF – was able to bind to DNA (our genetic code) and change how it behaves. This is how levels of the hormone EPO increase in low oxygen.

Further work showed HIF is constantly being made by cells, but it is constantly destroyed when oxygen levels are normal.

The agent of destruction is another protein called VHL, but where does oxygen come into this?

The last breakthrough showed showed HIF and VHL could chemically react only when there was enough oxygen around.

So to tell the story in the correct order: when oxygen levels fall, VHL can no longer stick to HIF, so HIF levels build up and it is able change the way our DNA works.

How is this helping treat disease?

Understanding and then manipulating the body’s oxygen-sensing abilities is leading to ideas for new treatments.

Drugs that tap into the oxygen-sensing system to boost red blood cells may also be an effective treatment for anaemia.

Meanwhile in cancer, tumours can hijack the process to selfishly create new blood vessels and make it easier for the cancer to grow.

So drugs to reverse the process might help stop cancers from growing.

The role of oxygen-sensing is also being investigated in diseases from heart failure to chronic lung disease.

“The work of these three scientists and their teams has paved the way to a greater understanding of these common, life-threatening conditions and new strategies to treat them,” Dr Andrew Murray from the University of Cambridge.

He added: “Congratulations to the three new Nobel Laureates, this is richly deserved!”

Previous winners

2018 – James P Allison and Tasuku Honjo for discovering how to fight cancer using the body’s immune system

2017- Jeffrey Hall, Michael Rosbash and Michael Young for unravelling how bodies keep a circadian rhythm or body clock

2016 – Yoshinori Ohsumi for discovering how cells remain healthy by recycling waste.

2015 – William C Campbell, Satoshi Ōmura and Youyou Tu for anti-parasite drug discoveries.

2014 – John O’Keefe, May-Britt Moser and Edvard Moser for discovering the brain’s navigating system.

2013 – James Rothman, Randy Schekman, and Thomas Sudhof for their discovery of how cells precisely transport material.

2012 – Two pioneers of stem cell research – John Gurdon and Shinya Yamanaka – were awarded the Nobel after changing adult cells into stem cells.

2011 – Bruce Beutler, Jules Hoffmann and Ralph Steinman shared the prize after revolutionising the understanding of how the body fights infection.

2010 – Robert Edwards for devising the fertility treatment IVF which led to the first “test tube baby” in July 1978.

2009 – Elizabeth Blackburn, Carol Greider and Jack Szostak for finding the telomeres at the ends of chromosomes.

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BBC News – Health

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