American Andrew Z. Fire shares Nobel Prize for discov...( ith a very different purpose. More than...)

ith a very different purpose. More than 15 years ago, Fire became interested in understanding the genes involved in the earliest steps of cellular development. He wanted to know how, in just 12 hours, a fertilized egg of the tiny soil-dwelling worm Caenorhabditis elegans changes from one cell to over 500, neatly arranged into body structures. To understand this complexity, Fire and technician Susan White-Harrison designed an experiment to increase gene expression--that is, to turn on a specific gene--to see if they could plot the steps involved in cellular development from the beginning. They injected the worm with a piece of DNA called a promoter, which initiates the synthesis of messenger RNA (mRNA). But the mRNA didn't do what they expected. Instead of turning the gene on, it inactivated it.

These results sat on the shelf for some time, bolstered along the way by observations by other animal and plant biologists that small amounts of sense RNA could apparently turn genes off. Then the puzzle deepened: graduate student Sam Driver in Mello's lab discovered that just one injection of RNA into a worm's body cavity could inactivate genes throughout the entire animal. It appeared that something both potent and stable was turning genes off.

A key experiment in Fire's lab later provided the explanation for what was happening--the researchers mixed sense RNA with a small amount of antisense RNA, and the two strands together generated the silencing effect. It was found that the earlier experiments had included trace amounts of antisense RNA, thus causing the RNA interference.

The Man behind the Prize

Fire, a California native, received an A.B. in mathematics from the University of California, Berkeley, in 1978. He went to the Massachusetts Institute of Technology (MIT) for graduate work, studying RNA polymerase type 2 transcription under Phillip Sharp, a Nobel laureate in gene research. Fire received his Ph.D. from MIT in 1983 and won a Helen
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Contact: Tina McDowell
tmcdowell@ciw.edu
202-939-1120
Carnegie Institution
2-Oct-2006

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