Peter Radcliffe read Medicine at CaiusSecretaría de Ciencia, Tecnología e Innovación Productiva

This week, the Nobel Prize in Physiology or Medicine was jointly awarded to Sir Peter Ratcliffe, William Kaelin Jr, and Gregg Semenza, for their work on how cells sense and respond to fluctuations in oxygen availability. 

A few minutes without oxygen and things go downhill very quickly. Mitochondria in our cells use oxygen to allow for the large-scale production of ATP from food and our energy reserves, something all eukaryotes have in common. 

Oxygen sensing is important for regulation of erythropoietin, a hormone which stimulates the production of red blood cells (which bind and transport oxygen to tissues). One of the early results from this group of scientists, was precisely how oxygen is able to control the production of EPO at a molecular level. When oxygen levels drop, a transcription factor (essentially a protein complex) called hypoxia-inducible factor (HIF), binds the DNA segment next to the EPO gene, and increases its production. This means that when oxygen levels are low, this helps us produce more red blood cells, useful if you want to climb Everest, and long exploited by athletes training at high altitudes.


Mountain View

Cambridge alumnus awarded Nobel Prize in Medicine

What they then discovered was that this particular mechanism was actually active in numerous cell types, and is a highly conserved gene transcription programme. When cells have high oxygen levels, there are low levels of HIF-1α, as oxygen directs its active degradation. Yet when oxygen levels in the cell drop, this degradation is inhibited, and HIF can accumulate and bind to its targets in the nucleus. The exact mechanics of how degradation occurs, is inhibited, and regulated, comprised a large part of this group’s research, and is a fundamental contribution to biology.

Now, you might think this only of use to those wanting to win the Olympics, but hypoxia signalling is critical in a number of physiological and disease processes, ranging from exercise, fetal development, to renal failure and cancer progression. The wide range of processes that are impacted by hypoxia signalling also means that we may be able to use this to fight against a number of diseases - or to finally climb that mountain.

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