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Medicine Nobel awarded for study on how human cells sense and adapt to oxygen levels

The findings by scientists William G. Kaelin Jr, Sir Peter J. Ratcliffe, and Gregg L. Semenza are relevant to nearly all bodily functions and mechanisms.

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Bengaluru: The 2019 Nobel Prize in Physiology or Medicine has been jointly awarded to scientists William G. Kaelin Jr, Sir Peter J. Ratcliffe, and Gregg L. Semenza for their research into how human cells “sense and adapt to oxygen availability”.

In its citation, the Nobel committee said the researchers have “identified molecular machinery that regulates the activity of genes in response to varying levels of oxygen”.

— The Nobel Prize (@NobelPrize) October 7, 2019

The researchers are affiliated with Harvard University (US), Francis Crick Institute (UK), and Johns Hopkins University (US), respectively.

The findings have wide implications for understanding diseases like cancer and are relevant to nearly all bodily functions and mechanisms.

Award-winning research

Oxygen is needed to sustain life and cellular function, but how exactly do oxygen fluctuations regulate cell adaptation has remained a mystery. When oxygen levels are low — ‘hypoxia’ — cells undergo changes in gene expressions to adapt to them. These changes alter the metabolism and processes of the body and cells.

In the 1990s, Gregg L. Semenza identified a transcription factor that regulates oxygen-dependent responses. Called Hypoxia Inducible Factor (HIF), it senses changes in oxygen levels and is a key regulator in changing cell metabolism. It consists of two components: the proteins HIF-1α and ARNT. HIF-1α is produced by all cells in a hypoxic environment but is destroyed when oxygen levels increase, said the citation.

At around the same time, William G. Kaelin Jr. was independently studying cancer, specifically a tumour suppression gene called the von Hippel-Lindau (VHL). He was able to show that this gene could suppress tumour growth in patients with VHL mutations, it said.

Later, Peter J. Ratcliffe demonstrated that there was a link between HIF-1α and VHL, and that VHL regulated HIF-1α’s degradation when oxygen levels climbed.

The latter two scientists then together showed that the HIF-1α undergoes a process called ‘hydroxylation’ in the presence of oxygen, which then degrades it, causing cell mechanisms to change subsequently, added the citation.

These findings have already influenced pharmacology and their applications in clinical trials to treat disease have shown positive results.

They could potentially aid in treating cancers better by slowing down the rate of progression of tumours. They also have applications in treating diseases relating to cardiovascular function such as stroke, hypertension, and heart attacks, as well as in immune function and physical wounds.

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