Brief about Nobel Prize.
The will of Swedish chemist engineer and Industrialist Alfred Nobel established the five Nobel Prize in 1895.
The prize in Chemistry, Literature, Peace, Physics, and Physiology or Medicine work were first awarded in 1901 in 1968 Sweden’s Central Bank Sveriges Riksbank established the Sveriges Riksbank Prize in Economic Science in Memory of Alfred Nobel.
The year 2019 Nobel Prize in Medicine was awarded to the scientist whose work centered on information on how our cells absorb various levels of oxygen.
William G. Kaelin Jr., Sir Peter J. Ratcliffe, and Gregg L. Semenza discovered how cells can sense and adapt to change in oxygen.
The fundamental significance of oxygen is known for centuries.
Each person of trillions of cells and absolutely, all animals need oxygen anywhere on this planet and they use oxygen for the conversion of food into usable energy.
Oxygen at center stage.
Oxygen is essential for animal existence: it’s food utilized by the mitochondria found in genuinely all animal cells so one can convert food into usable energy.
Mitochondria are organelles, that generate most of the chemical energy. It is also known as the powerhouse of cells. Chemical energy produced by the mitochondria is stored in small molecules called adenosine triphosphate (ATP).
A mechanism developed during all animals’ evolution that ensures a sufficient supply of oxygen to every tissue and cell. There are two large blood vessels on both sides of the neck that contains a specialized cell that can sense the blood’s oxygen levels.
It has been observed that as one move to a higher altitude, oxygen levels in the blood decrease and this is because at a high altitude air becomes thin and oxygen in the air also decreases.
NOW, when the oxygen levels in the blood decrease, this decrease in oxygen are sensed by specialized cells in the kidney that makes Hormone Erythropoietin ( EPO ), this, in turn, increases the production of red blood cells in the bone marrow so increase in red blood cells in our body helps to coup up with low levels of oxygen (Hypoxia).
So now, a question has arisen that, How do cells sense and adapt to changes in levels of oxygen availability?
To find out the answer to this question the researchers exposed animal cells to various levels of oxygen and they discovered that the expression or transcriptions of many genes change when the oxygen levels change.
So to answer the question that how do cell sense and adapt to changes in levels of oxygen availability?
The Nobel Laureates William G. Kaelin Jr., Sir Peter J. Ratcliffe, and Gregg L. Semenza start discovering that can regulate the expression of EPO (the Hormone Erythropoietin) in low levels of oxygen (Hypoxia), and then they discovered the transcription factor known as HIF-1 Alpha (Hypoxia-Inducible Factor), So whenever there are low oxygen levels in our body then HIF-1 Alpha starts bonding with DNA and then bonds with one gene to produce EPO (the Hormone Erythropoietin).
EPO is a hormone produced by the Kidney, Hormone Erythromycin (EPO) leads to increased production of Red Blood Cells ( Erythropoiesis).
That’s means if there is a lack of oxygen in our body then the kidney starts producing more EPO.
And, If there is the lowest level of oxygen(Hypoxia Condition) then HIF-1 Alpha helps in producing more Red Blood Cells, or if there is a sufficient supply of oxygen then HIF-1 Alpha get hydroxylated, and this occurs at Normoxia (Norman Levels Of Oxygen), a cellular machine called the proteasome (Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases), degrades HIF-1 Alpha. Under such conditions, a small peptide, ubiquitin, is introduced to the HIF-1 Alpha protein. Ubiquitin features as a tag for proteins destined for degradation inside the proteasome.
Now another question arises, how ubiquitin binds to HIF-1Alpha in an oxygen-dependent manner?
The answer was unexpected, Semenza and Ratcliffe were exploring the regulation of the EPO gene, and William Kaelin, Jr. was researching an inherited syndrome, Von Hippel-Lindau’s disease (VHL disease). This genetic disease leads to a conclusively increased risk of certain cancers in families with inherited VHL mutations.
VHL gene encodes a protein that forestalls the onset of cancer, and also most cancers cells lacking a useful VHL gene explicit abnormally high levels of hypoxia-regulated genes, but that once the VHL gene became reintroduced into cancer cells, ordinary tiers had been restored. This was a significant intimation that VHL changed into someway concerns in controlling responses to hypoxia.
and according to several researcher groups, VHL is part of a complex that labels proteins with ubiquitin, marking them for degradation in the proteasome.
Ratcliffe and his research group discovered that that VHL can physically interact with HIF-1 Alpha and is required for its degradation at normal oxygen levels. This conclusively linked VHL to HIF-1 Alpha.
Summary about Scientists who got the 2019 Nobel prize in Physiology or Medicine.
WILLIAM BILL G. KAELINJR JR. (Born in 1957 in New York City) is a professor of medicine at Harvard University and the Dana-Farber Cancer Institute.
His laboratory study tumor suppressor protein Kaelin is a 2016 recipient of the Lasker Award for Basic Medical Research.
He is a 2019 Nobel Laureate in Physiology or medicine with Peter J Ratcliffe and George L. Semenza.
Sir, Peter J Ratcliffe
Sir, Peter J Ratcliffe, (Born 14th May 1954) is a British Physician-Scientist he was a practicing clinical at the John Radcliffe Hospital, Oxford, and Nuffield Professor of Clinical Medical and head of the Nuffield Department of Clinical Medicine at the University of Oxford from 2004 to 2016.
In 2016 he become clinical research Director at the Francis Crick Institute.
Ratcliffe is best known for his work on cellular reactions to hypoxia for which he shared the 2019 Nobel Prize in Physiology or Medicine with William Kaelin Jr. and Gregg L. Semenza.
Gregg L. Semenza.
Gregg Leonard Semenza (Born July 1, 1956) is a professor of pediatrics, radiation, and oncology at the Johns Hopkins University School of Medicine.
He serves as the Director of the Vascular Program at the Institute for Cell Engineering. He is a 2016 recipient of the Lasker Award for Basic Medical Research.
He is for his discovery of HIF-1, which allows cancer cells to adapt to oxygen-poor environments. He received the 2019 Nobel Prize in Physiology or Medicine Ratcliffe.
The Nobel Prize in Physiology or Medicine 2019