Two Americans shared this year's Nobel Prize in Chemistry for deciphering the communication system that the human body uses to sense the outside world and send messages to cells — for example, speeding the heart when danger approaches.
Two Americans shared this year’s Nobel Prize in Chemistry for deciphering the communication system that the human body uses to sense the outside world and send messages to cells — for example, speeding the heart when danger approaches. The understanding is aiding the development of new drugs.
The winners, Dr. Robert Lefkowitz, 69, a professor at the Duke University Medical Center in Durham, N.C., and a Howard Hughes Medical Institute researcher, and Dr. Brian Kobilka, 57, a professor at the Stanford University School of Medicine in California, will split $1.2 million.
Lefkowitz and Kobilka filled in a major gap in the understanding how cells work and respond to outside signals.
Scientists already knew, for example, that stress hormones like adrenaline trigger the body’s fight-or-flight reflex — focusing vision, quickening breathing, diverting blood away from less urgent body systems like the digestive tract — but adrenaline never enters the cells.
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“A receptor was correctly assumed to be involved,” said Sven Lidin, a member of the Nobel Prize committee for chemistry during a news conference of the Royal Swedish Academy of Sciences in Stockholm, which awards the Nobels, “but the nature of this receptor and how it reacted remained a mystery for a long time.”
Lefkowitz said although the notion of cell receptors goes back more than a century ago, “When I kind of started my work in the area in the early ’70s, there was still a lot of skepticism as to whether there really was such a thing.”
By attaching radioactive iodine to a hormone, Lefkowitz was able to track the movement of the hormone and explore the behavior of these receptors. Over the years, he was able to pull out the receptor proteins and show they were specific molecules.
In the 1980s, his group, which included Kobilka as a postdoctoral researcher, searched for and found the gene that produced one of these protein receptors.
The genetic blueprint indicated that the shape of the protein included long spirals that wove through the cell membrane seven times.
Meanwhile, other researchers had discovered a class of proteins, called G proteins, inside the cell that, when activated, set off a Rube Goldberg cascade of molecular machinery.
The receptor was the last missing piece.
“If you have something like adrenaline, it sticks in there, turns the key, changes the shape of the receptor, and now the receptor, having changed shape, is able to tickle the G protein,” Lefkowitz said.
There was a “eureka moment,” Lefkowitz said, when he realized that his receptor was the same as another receptor that had been found in another part of the body — the light receptor rhodopsin in the retina.
Within a year, they were able to decode the genetic blueprints for several other similar receptors.
About 1,000 of these receptors, known as G protein-coupled receptors, are now known, residing on the surface of cells and reacting to a host of hormones and neurotransmitters.
Lidin of the Royal Swedish Academy said that it turned out that half of all drugs target such receptors.