This year’s Nobel Prize in Physiology or Medicine was jointly awarded to William G. Kaelin, Gregg L. Semenza, Peter J. Ratcliffe for their discoveries of how cells sense and adapt to oxygen availability.
Erythropoietin (EPO) is a hormone that promotes the production of more red blood cells when oxygen level is low. For instance, an individual’s EPO level will increase when subjected to very high altitudes where the oxygen level is very low. Interestingly, Semenza discovered a protein complex that binds to regulatory sequences of the EPO gene. He named this protein complex hypoxia-inducible factor (HIF) that was subsequently found to comprise two different transcription factors which are HIF1α and ARNT. When oxygen level is high, HIF1α is low. However, when oxygen level is low, HIF1α level is high. Ratcliffe also researched on the oxygen-dependent regulation of the EPO gene and both scientists concurred that a molecular switch regulating how cells sense and adapt to varying oxygen levels was present in all cells (not only the kidney cells).
Kaelin’s research was on a type of genetic disease known as the von Hippel-Lindau’s disease (VHL disease). It was found that this disease led to an increased risk of particular types of cancers in families with the inherited VHL mutation. Kaelin showed that the VHL gene encodes a protein that prevents cancers from arising. Building on Kaelin’s findings, Ratcliffe subsequently discovered that the VHL protein destroys HIF1 α when oxygen level is at normal levels. Today, a drug that is based on their research findings is currently in used to treat certain types of cancer.
The seminal research findings of these three scientists pave our understanding of how cells respond to oxygen availability and what molecular switches are involved in this regulation. More importantly, understanding these cellular mechanisms allow us to better combat conditions and diseases such as anaemia, cancer and diabetes.
Click here to find out more about these Nobel laureates’ research work.
Comments