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University researchers play role in Nobel Prize for Chemistry

By Anna Rozenberg, Daily Staff Reporter
Published October 12, 2012

Once again, the University of Michigan’s researchers were part of one of science’s fundamentally changing breakthroughs — though this time the results earned scientists a Nobel Prize in chemistry.

Robert Lefkowitz, of Duke University, and Stanford University's Brian Kobilka were awarded the Nobel Prize on Oct.10 for their study of how g-protein linked receptors react to certain cellular signals in the body.

G-protein linked receptors are a type of receptor found on the membrane, or lining, of humans’ body cells. The extracellular side of the receptors, or the part exposed to the outside of the cell, is able to pick up specific hormones that change the conformation of the g-protein linked receptor.

The change in conformation causes a specific type of protein, a g-protein found on the intracellular or inside of the receptor and cell, to activate and jumpstart various signaling cascades within the cell. Signaling cascades are a chain of reactions that cause the cell to perform certain functions.

Georgios Skiniotis, an assistant professor of biological chemistry at the University and an assistant research professor in the Life Sciences Institute, contributed to the research for the past three years by helping to figure out the perfect conditions for studying the g-protein linked receptors in vitro, or in a lab rather than the human body.

“(Signaling cascades) are involved in pretty much every aspect of human or animal physiology,” he explained. “It’s the main means of communication between the cell and its environment.”

The understanding of g-protein linked receptors has been studied for years and is a key component to the advancement of creating new drugs, according to Skiniotis.

Skiniotis said his part in the project was obtaining the structure of the g-protein linked receptor when it activates a g-protein.

“The idea was that this happens in cell but we want to get the structure ... so we need to isolate it (in vitro),” Skiniotis said.

Roger Sunahara, an assistant professor in the University's Department of Pharmacology and a key researcher working under Kobilka on the project, described the complex they were studying as an old-fashioned switchboard for telephone calls.

“Receptors are like the phone call, g-proteins are like the switchboard operator that connects you to the people you want to call,” he said. “I’ll be one phone call and talk to one g-protein but that one g-protein may talk to many affecters.”

Sunahara explained that there is always signal amplification in signal transduction so that one activated g-protein can cause many pathways and in turn cause the cell do start or stop certain things.

“What we’ve been interested in is trying to figure out how the receptor when it recognizes a hormone how does it turn the g-protein on from a molecular perspective,” he said.

While Kobilka’s research has been going on for years, the project culminated last year with their paper that describes the mechanism in atomic detail, according to Sunahara. He added that they were able to document each atom and its position in the structure.

Sunahara said that in terms of the big picture of science, their discovery could help to create more efficient, safe drugs with fewer side effects.

He explained that many side effects are caused by a drug not being specific to its targeted receptor, potentially causing other receptors to be targeted on accident.

“Now we can go back to the structure of the receptor and say, ‘Well why don’t we design a better drug that can target the surface of the receptor a little better?’”

Skiniotis said that while the researchers knew the gravity of their work and that it might generate a Nobel Prize, their success happened faster than expected.

“Getting this structure was really considered a holy grail in the field,” he said. “It was a very difficult target but it was a very significant target at the same time.”

NOTE TO WHOEVER: I'm sending the researcher their quotes to make sure everything is factual -- it's a tricky subject!

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