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Fuelling the fire of life and the 2019 Nobel Prize

William Kaelin Jr., Sir Peter Ratcliffe, and Gregg Semenza has been awarded this year's prize for their characterisation of the hypoxia inducible factor (HIF), and how the function of this transcription factor is directly coupled to oxygen levels - making it an oxygen sensor. That oxygen is important for energy production in living organisms is old knowledge.
... In fact, Nobel prizes related to the sensing of oxygen has been awarded two times before. In 1931, Otto Warburg was awarded the prize for discovering the enzymatic basis of cellular respiration, and in 1938, Corneille Heymans was awarded for elucidating the role of the nervous system in respiratory responses to changes in oxygen availability. And now, the desire of scientists to understand the important process of oxygen sensing, all the way down to the molecular workings, has led to a third Nobel Prize. While HIF today is known to control various pathways and the expression of many different genes, the path to the Nobel Prize in 2019 is perhaps best illustrated by focusing on the physiological process that was central to the discovery. Already in the late 1800s it was realised that high altitude hypoxia in humans lead to an increase in the number of circulating red blood cells. This response is activated by the hormone erythropoietin (EPO), which stimulates production of red bloods cells in the bone barrow. The increase in red blood cells increases the oxygen carrying capacity of the blood, thereby compensating for the reduction in the saturation level of haemoglobin caused by hypoxia. In other words, each haemoglobin will carry less oxygen, but by having more haemoglobin in the blood, oxy gen supply can be maintained. A century later, it was determined that hypoxia leads to an increase in the express ion of the gene coding for EPO, and it was this background knowledge that led this years' Nobel laureates to ask the questions - what initiates the change in gene express ion and how is it coupled to oxygen?

How was HIF discovered?
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