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Tuesday 20th March 2018

Trio Win Nobel Medicine Prize for Work on How Cells Adapt to Oxygen

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7Dnews London

Mon, 07 Oct 2019 20:20 GMT

The Nobel prizes have been awarded to men, women and organisations whose work has led to great advances for mankind in line with the wishes of Alfred Nobel since 1901.

The 2019 Nobel Prize for Physiology or Medicine was awarded on Monday October 7th to two Americans and a British scientist for their discoveries in how the body’s cells sense and adapt to oxygen levels, opening new strategies to fight common diseases such as cancer and anaemia.

William Kaelin and Gregg Semenza of the US and Britain's Peter Ratcliffe split the nine million Swedish krona ($914,000, €833,000) award, according to AFP.

Announcing the prize, the Nobel Assembly at the Karolinska Institute in Stockholm, Sweden, said the work by the three laureates has “greatly expanded our knowledge of how physiological response makes life possible”.

It said Semenza, Ratcliffe and Kaelin found “the molecular switch for how to adapt” when oxygen levels in the body vary, noting that the most fundamental job for cells is to convert oxygen to food and that cells and tissues constantly experience changes in oxygen availability.

"They established the basis for our understanding of how oxygen levels affect cellular metabolism and physiological function. Intense ongoing efforts in academic laboratories and pharmaceutical companies are now focused on developing drugs that can interfere with different disease states by either activating, or blocking, the oxygen-sensing machinery," the Nobel jury stated.

Semenza studied the EPO gene and how it is regulated by varying oxygen levels. By using gene-modified mice, specific DNA segments located next to the EPO gene were shown to mediate the response to hypoxia.

Ratcliffe also studied O2-dependent regulation of the EPO gene and both research groups found that the oxygen-sensing mechanism was present in virtually all tissues, not only in the kidney cells where EPO is normally produced.

These were important findings showing that the mechanism was general and functional in many different cell types. Semenza wished to identify the cellular components mediating this response.

The answer came from an unexpected partner. At about the same time as Semenza and Ratcliffe were exploring the regulation of the EPO gene, cancer researcher Kaelin was researching an inherited syndrome (VHL disease). This genetic disease leads to dramatically increased risk of certain cancers in families with inherited VHL mutations.

Kaelin showed that the VHL gene encodes a protein that prevents the onset of cancer. He proved that cancer cells lacking a functional VHL gene express abnormally high levels of hypoxia-regulated genes. However, when the VHL gene was reintroduced into cancer cells, normal levels were restored.

The trio’s work has shed new light on the specific, cell-level processes the body undergoes when low on oxygen. Cells' oxygen-sensing ability is also essential during fetal development and in creating new blood vessels.

Kaelin, 61, works at the Howard Hughes Medical Institute in the US, while Semenza, 63, is director of the Vascular Research Program at the Johns Hopkins Institute for Cell Engineering.

Ratcliffe, 65, is director of clinical research at the Francis Crick Institute in London and director of the Target Discovery Institute in Oxford.

The announcement of the Nobel Medicine Prize kicked off Nobel week. The Karolinska Institute received 633 nominations for the prize.

There will be announcements for the prize for physics on Tuesday, chemistry on Wednesday, literature on Thursday, and economics on Monday October 14th, according to AP.

This year’s Literature Prizes is double-headed, with one each for 2018 and 2019, as the 2018 literature prize was suspended after a scandal rocked the Swedish Academy.

Unlike the other Nobels awarded since 1901, the Economics Prize is the only one not created by the prizes' founder, philanthropist and dynamite inventor Alfred Nobel. It was devised in 1968 to mark the 300th anniversary of Sweden's Central Bank and first awarded in 1969.

The Peace Prize will be awarded in Oslo on Friday October 11th, with Swedish teen climate activist Greta Thunberg seen as the favourite on betting sites such as Ladbrokes.

This year, the Norwegian Nobel Committee disclosed that it received 301 nominations for the Peace Prize.

Other names circulating for the honour are Ethiopian Prime Minister Abiy Ahmed, who clinched a peace deal with arch foe Eritrea, and NGOs such as Reporters without Borders and the Committee to Protect Journalists.

Predictions about possible winners are notoriously difficult as the prize-awarding institutions keep the names of the nominees secret for 50 years.

This year, Nobel glory comes with a nine-million-krona ($918,000) cash award, a gold medal and a diploma. The laureates receive them at ceremonies in Stockholm and Oslo on December 10th, the anniversary of Alfred Nobel’s death in 1896.


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