Researchers awarded the Nobel Prize in Medicine for their discovery of cells adapting to low oxygen

The Nobel Assembly has awarded the 2019 Nobel Prize in Physiology or Medicine to William Kaelin, Sir Peter Ratcliffe, and Gregg Semenza for their discoveries of the ways in which cells sense and adapt to the availability of oxygen.

The molecular switch that helps our cells to adjust to lowering oxygen levels was discovered by the three researchers. This is necessary because it offers a hypoxic reaction when the oxygen levels change i.e. the change when altitude changes, when exercising or when getting a cut.

There are various ways by which our body handles this such as forming new blood vessels, increase of blood cell production, cells adapting to certain metabolic changes. An example of the latter situation is the production of lactic acid in muscle cells during heavy exercise. The energy captured in food is released by the cells using oxygen in a reaction called aerobic respiration. Cells can also perform anaerobic respiration to avoid using oxygen but this is not sustainable as well as inefficient in the long term for humans. The three Nobel laureates and their colleagues discovered this ability to switch from one mode to the other.

It is known that the increase in the erythropoietin hormone (EPO) is produced by the kidneys in low-oxygen conditions and in anemic people. Semenza, working at Johns Hopkins University demonstrated that the increase in EPO which stimulates the production of red blood cells is stimulated by a specific gene known as hypoxia response element or HRE.

HIF-1α is one of the proteins produced by the gene found to be oxygen sensitive which disappears in the abundance of oxygen. The cells were more likely to show symptoms of hypoxia which lack the von Hippel-Lindau gene (connected to cancer). This was discovered by William Kaelin and his team from the Dana-Farber Cancer Institute.

A relation between VHL and HIF-1α was created by Ratcliffe and his group from Oxford University and the Francis Crick Institute. They figured out the molecular details of the working of these mechanisms and also that the protein cannot be destroyed without the gene. From general metabolism and exercise response to embryo development and the functioning of the immune system, HIF-1α plays very crucial roles. It also affects conditions like anemia, cancer, strokes, and heart attacks. At present, EPO is being studied as a potential method to fight against the cancer cells by preventing them access to oxygen and nutrients.

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