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"Superb award for basic research"

News: Oct 07, 2019

The recipients of this year’s Nobel Prize in Physiology or Medicine have identified how cells adapt to varying oxygen levels — molecular machinery that is essential to life. Their discoveries are described as groundbreaking.

“This is a superb award in terms of basic research,” says Bengt Hallberg, professor of medical biochemistry at Sahlgrenska Academy, University of Gothenburg.

Three researchers share the Prize: William G. Kaelin, Jr., Sir Peter J. Ratcliffe, and Gregg L. Semenza. Their achievement has been to identify something that had long been a mystery: how, at molecular level, cells sense and, through gene regulation, respond to the ambient oxygen supply.

Key concepts include the erythropoietin (EPO) gene and two DNA-binding proteins known as HIF-1α and ARNT. By researching these, the three Laureates have been able to piece the evidence together and find out which additional components affect cellular physiology in hypoxia (low oxygen levels).

High-altitude training

Hallberg cites high-altitude training as an example of how the machinery works. When athletes train at a high altitude, thus experiencing hypoxic conditions, the body responds by producing more red blood cells. This boosts oxygen-uptake (aerobic) capacity and improves athletes’ performance even after they have returned to a normal altitude.

“If oxygen’s in short supply, the body senses it and makes more red blood cells through HIF-1α and EPO. And that’s what they’ve clarified, how this works mechanically, and also how the degradation takes place,” Hallberg says.

“But oxygen regulates many more processes as well — infections, anemia, wound healing, and tumor growth — and they’re interconnected in a highly intricate way. Tumors need oxygen to grow but, through another signaling pathway, HIF-1α also regulates the formation of new blood vessels.”

Cancer and diabetes

Patrik Rorsman, professor of cellular endocrinology at Sahlgrenska Academy, University of Gothenburg, is well acquainted with one of the three scientists who are to share this year’s Nobel Prize. Sir Peter Ratcliffe has been Director of the Target Discovery Institute in the University of Oxford’s Nuffield Department of Medicine, and Rorsman still leads a small research group there.

“The Oxford department Peter Ratcliffe used to head is the size of a small Swedish university. He’s an impressive person, who also works clinically as a doctor, and it has long been speculated that he should receive the Nobel Prize in Medicine for discovering how cells sense and adapt to the supply of oxygen,” says Rorsman, who is delighted with Ratcliffe’s success.

The findings on how cells use oxygen are of the utmost importance for cancer research, where researchers worldwide are now working to find ways of using the mechanism to suffocate tumors.

But the prizewinning discoveries are also of great importance in Rorsman’s research area, diabetes. One theory is that the mechanisms now discovered, for which the Nobel Prize is now being awarded, set off a vicious circle in beta cells, which may explain why type 1 diabetes is a progressive disease.

“The beta cells really need a lot of oxygen to produce insulin, and if the mechanism is impaired, diabetes is induced,” Rorsman says.

“We’ve studied a mitochondrial enzyme that accumulates in diabetes and becomes less active. We think that may partly explain why diabetes is often a mild disease initially, but gets worse over time.”

Images: Thomas Perlmann, Nobel Assembly at Karolinska Institutet (photo: Erik Flyg), headshots of Bengt Hallberg (photo: Malin Arnesson) and Patrik Rorsman (photo: Johan Wingborg).

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Page Manager: Pontus Sundén|Last update: 8/8/2018
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