Nobel prize in chemistry 2012 for work on cell receptors
this may be the first Nobel prize in chemistry awarded to two medical doctors.
Americans Robert J Lefkowitz and Brian K Kobilka have won this year's chemistry Nobel for their work on G-protein-coupled receptors, which allow cells to sense light, flavour, odour and receive signals from hormones and neurotransmitters
Biological emphasis of this year's Nobel prize in chemistry. The field of chemical biology is burgeoning because at its heart, at the heart of certainly cell biology, is an understanding at the molecular level of what's going on and that's chemistry essentially. So other sorts of chemistry are still going on and still very important, but this level of understanding which has been made possible by advances in techniques over the last 20 years or so is crucial to mankind....biological field, because it's so crucial that we understand the molecular processes that are going on in cells in animal and human bodies.
Kobilka said when the phone call first came in from Stockholm, he thought it was a crank call or a wrong number."Then
it rang again. You get congratulated by these members of the Swedish
committee and things happen pretty fast," he said in a telephone
interview from his home In Palo Alto, California.
He
said he was being recognized primarily for his work in determining the
structure of the receptors and what they look like in three dimensions.
"Probably the most high profile piece of work was published last year, where we have a crystal structure of the receptor activating the G protein. It's caught in the act of signaling across the membrane," he said.
Nutshell
# Two American scientists won the 2012 Nobel Prize for chemistry on
Wednesday for research into how cells respond to external stimuli that
is helping to develop better drugs to fight diseases such as diabetes,
cancer and depression.
# The Royal Swedish Academy of Sciences said the 8 million crown ($1.2
million) prize went to Robert Lefkowitz, 69, and Brian Kobilka, 57, for
discovering the inner workings of G-protein-coupled receptors, which
allow cells to respond to chemical messages such as adrenaline rushes.
# “Around half of all medications act through these receptors, among them beta blockers, antihistamines and various kinds of psychiatric medications,” the Nobel Prize committee said.
# Working out better ways to target the receptors, known as GPCRs, is an area of keen interest to pharmaceutical and biotechnology companies.
# GPCRs are linked to a wide range of diseases, since they play a central role in many biological functions in the body, but developing new drugs to target them accurately has been difficult because of a lack of fundamental understanding as to how they function. Experts say the work of the Nobel Prize winners has opened the door to making better medicines.
# Drugs targeting GPCRs have potential in treating illnesses involving the central nervous system, heart conditions, inflammation and metabolic disorders.
# "This ground-breaking work spanning genetics and biochemistry has laid the basis for much of our understanding of modern pharmacology as well as how cells in different parts of living organisms can react differently to external stimulation,"
# "Out of the roughly 1,400 drugs that exist in the world, about 1,000 of them are little pills that you consume, and the majority of these are based in these receptors,
Transmembrane receptor:E=extracellular space; I=intracellular space; P=plasma membrane |
This from the Nobel Assembly press material:
Your body is a fine-tuned system of interactions between billions of cells. Each cell has tiny receptors that enable it to sense its environment, so it can adapt to new situtations. Robert Lefkowitz and Brian Kobilka are awarded the 2012 Nobel Prize in Chemistry for groundbreaking discoveries that reveal the inner workings of an important family of such receptors: G-protein–coupled receptors.
The seven-transmembrane α-helix structure of a G-protein-coupled receptor |
And more to share:
For a long time, it remained a mystery how cells could sense their environment. Scientists knew that hormones such as adrenalin had powerful effects: increasing blood pressure and making the heart beat faster. They suspected that cell surfaces contained some kind of recipient for hormones. But what these receptors actually consisted of and how they worked remained obscured for most of the 20th Century.
Lefkowitz started to use radioactivity in 1968 in order to trace cells' receptors. He attached an iodine isotope to various hormones, and thanks to the radiation, he managed to unveil several receptors, among those a receptor for adrenalin: β-adrenergic receptor. His team of researchers extracted the receptor from its hiding place in the cell wall and gained an initial understanding of how it works.
The team achieved its next big step during the 1980s. The newly recruited Kobilka accepted the challenge to isolate the gene that codes for the β-adrenergic receptor from the gigantic human genome. His creative approach allowed him to attain his goal. When the researchers analyzed the gene, they discovered that the receptor was similar to one in the eye that captures light. They realized that there is a whole family of receptors that look alike and function in the same manner.
Today this family is referred to as G-protein–coupled receptors. About a thousand genes code for such receptors, for example, for light, flavour, odour, adrenalin, histamine, dopamine and serotonin. About half of all medications achieve their effect through G-protein–coupled receptors.
The studies by Lefkowitz and Kobilka are crucial for understanding how G-protein–coupled receptors function. Furthermore, in 2011, Kobilka achieved another break-through; he and his research team captured an image of the β-adrenergic receptor at the exact moment that it is activated by a hormone and sends a signal into the cell. This image is a molecular masterpiece – the result of decades of research.
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