US scientists win chemistry Nobel Prize

Two Americans, Robert Lefkowitz and Brian Kobilka, have shared the 2012 Nobel chemistry prize for discovering how microscopic receptors on the surface of a living cell enable it to detect external signals.

By revealing the inner workings of so-called G-protein coupled receptors or GPCRs, the laureates helped biologists to understand how cells sense stimuli such as light and smells. These receptors are also responsible for cells’ reactions to biochemical molecules in the body such as adrenalin, histamine and dopamine – making them a prime target for the drugs industry.

“Half of all medications achieve their effect through G-protein coupled receptors,” said chemistry professor David Phillips of Imperial College London. “It is no surprise that Lefkowitz and Kobilka have been awarded this year’s Nobel Prize because these receptors have such a vital implication for human health.”

Prof Lefkowitz, 69, started to investigate how cells respond to hormones while working at the US National Institutes of Health in the late 1960s, but he has spent most of his career at Duke University, North Carolina.

He began by using adrenalin, labelled with radioactive iodine atoms, to see how cells respond to the hormone. With colleagues he extracted the receptor from its hiding place in the cell wall and gained an initial understanding of how it works.

But the biggest breakthrough came in the 1980s when Prof Kobilka, now 57, joined Prof Lefkowitz’s biochemistry team at Duke. Together they decoded the gene for the adrenalin receptor and then realised that it was similar to one with a completely different function – detecting light in the eye.

That led to the conclusion that cells have a large family of receptors, now known as GPCRs, that work in the same way while responding to a wide variety of stimuli. Today about 1,000 different GPCRs are known.

Both men have continued research in the area. Last year Prof Kobilka and colleagues captured an image of the adrenalin receptor at the exact moment when it is activated by a hormone and sends a signal into the cell. “This image is a molecular masterpiece,” said the Royal Swedish Academy of Sciences in its Nobel citation.

Meanwhile pharmaceutical companies continue to develop new drugs targeting GPCRs. “The insights we have into GPCR structure and function as a result of the pioneering work of the labs of Lefkowitz and Kobilka are crucial to the development of new and safer medicines for patients, who may currently have limited options,” said Fiona Marshall, chief scientist at Heptares Therapeutics of the UK.