Author: Alexia Ferreira, Yr 12
Discovered in 1771 by Carl Willhelm Scheele (German-Swedish pharmaceutical chemist), oxygen is a vital constituent of all living fauna and is central to everyday function in the human body. While biologists have long known the need and function of oxygen within the body, knowledge pertaining to how exactly cells detect and adapt to oxygen concentration had never been truly understood until Sir Peter Ratcliffe, William Kaelin and Gregg Semenza made a groundbreaking discovery.
The first mechanism the trio explored was the role of erythropoietin (EPO) in the production of red blood cells. When your body detects that blood oxygen levels are too low, EPO released by the kidneys acts as a hormone and signals to the bone marrow to increase the production of red blood cells – increasing the rate of oxygen the blood can transport. The three scientists then explored what is known as the Hypoxia-inducible factor (HIF) system, an integral part of their research concerned with how exactly the body copes with low levels of oxygen.
When the body experiences hypoxia, the liver unequivocally releases EPO as aforementioned; however, the scientists also discovered that HIF acts as a “switch” for the release of EPO - activating and deactivating the gene that codes for EPO within cells depending on the amount of oxygen within the external environment. What is interesting about their research is that it also showed how HIF is constantly produced within the body, positing the question: what happens when oxygen levels are normal? Their research also happened to provide an answer to this. A small protein called ubiquitin binds to the surface of HIF proteins and signals to cells that they must be destroyed; the levels of EPO production are then maintained at a normal level. The trio then theorized and consequently proved that when oxygen levels are too low HIF proteins will contain a hydroxyl group which signals to VHL complex (proteins responsible for binding ubiquitin to HIF) that the destruction of HIF is still necessary. When oxygen levels are normal-high, HIF does not contain the hydroxyl group, causing the opposite effect to take place within the body.
Perhaps it may seem futile to award scientists the prestigious Nobel Prize for simply figuring out a mechanism within the body; however, their findings prove to have the upmost importance in the future of medicine. Scientists have now begun research into suffocating tumors by shutting down their HIF systems. Anemia, a condition where the body produces cancerous red blood cells, for example, is a promising area for research since if scientists are able to replicate the HIF mechanism using a drug, it would prove as an effective treatment for cancer as the number of healthy red blood cells within patients would increase.
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