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RNA Interference Is Focus of Stetten Lecture, Oct. 22

By Alison Davis

It all started when scientists trying to genetically engineer purple petunias ended up with plain white ones instead. By trying to supply a color gene, the researchers had unexpectedly erased a trait instead of adding one.

Getting to the bottom of this mystery took a little luck and the careful eyes of a team of basic researchers working on something completely different. Dr. Andrew Fire of the Carnegie Institution of Washington in Baltimore and his colleague Dr. Craig Mello of the University of Massachusetts Medical School in Worcester were the ones to explain the curious finding. In so doing, the team christened a new technology, a powerful gene-silencing tool called RNA interference, or RNAi.

Fire will tell the story of RNAi at this year's DeWitt Stetten, Jr. Lecture, entitled "RNA-Triggered Genetic Silencing Mechanisms." The talk, which is part of the NIH Director's Wednesday Afternoon Lecture Series and is sponsored by NIGMS, will be held on Wednesday, Oct. 22 at 3 p.m. in Masur Auditorium, Bldg. 10.

Fire and Mello had been using a genetic approach called antisense RNA technology to find genetic factors involved in cell growth and development. In this technique, researchers use the anti-, or opposite, strand of RNA to zip up single-stranded RNA and keep it from being made into a protein. Eliminating a gene in an otherwise intact experimental organism can point researchers to the gene's function.

The experiments weren't working, but a little perseverance led Fire and Mello to find a contaminant in their test-tube preps. The contaminant, it turns out, was double-stranded RNA, and somehow it was turning off specific genes. In time, researchers learned that double-stranded RNA is a vital intermediate in the RNAi gene-silencing process.

What's helping out, scientists have discovered, is an enzyme called Dicer. This enzyme, aptly named, chops up the double-stranded RNA into little bits called short interfering RNAs, or siRNAs. These snippets of genetic material act like guided missiles. They team up with cell machinery that can destroy a specific messenger RNA with a precisely matched sequence to the siRNA and restrict the message from being expressed into a protein.

Although RNAi is a relative newcomer to molecular biologists, scientists know the process has deep evolutionary roots. Researchers believe this biological trick endows organisms with the ability to mute genes for the purposes of growth, as well as for self-defense against viruses.

Ten years after the initial lab discovery of RNAi, researchers across the globe have latched onto the technique as an extraordinarily useful tool for probing functional genomics, the science of discerning the biological function of genes and their products. Scientists are also excited about including RNAi in the toolkit for producing new kinds of molecule-based therapies. As a first step toward achieving that goal, several researchers have developed methods in which cells can be prodded to produce specific siRNAs on demand. In recent lab tests with lab-grown cells, for instance, researchers used an RNAi weapon to kill HIV.

Fire is a member of the scientific staff of the department of embryology at the Carnegie Institution of Washington in Baltimore and an adjunct professor of biology at Johns Hopkins University. After receiving a bachelor's degree in mathematics in 1978 from the University of California, Berkeley, he earned a doctorate in biology in 1983 from the Massachusetts Institute of Technology, working with Nobel laureate Dr. Phillip Sharp. He then worked as a postdoctoral fellow with Nobel laureate Dr. Sydney Brenner at the Medical Research Council Laboratory of Molecular Biology in Cambridge, U.K. Fire's many honors include winning the Genetics Society of America Medal and sharing the National Academy of Sciences Award in Molecular Biology and the Wiley Prize in the Biomedical Sciences.

NIGMS has supported Fire's research since he became an independent investigator in 1986.

For more information or for reasonable accommodation, call Hilda Madine at 594-5595.

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