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Could mutant flies give epilepsy sufferers greater peace of mind?
Date:3/21/2011

EUREKA "Exceptional, Unconventional Research Enabling Knowledge Acceleration" is the name of a rare and competitive grant that Reenan recently won from the National Institutes of Health. Beginning April 1, Reenan will use the four-year, $1.3-million award to look for genes that can suppress seizures in fruit flies that he has cleverly engineered to mimic human epilepsy.

The epiphany, which came a few years ago, was about the surprising genetic similarity between fruit flies and people. For years Reenan has conducted basic gene expression research on a particular fruit fly gene nicknamed "para" that governs how sodium ions can trigger brain cells to electrically signal muscles to move. Ominously, the gene's name is short for paralytic.

"I'd known for years that there are sodium channel-related genes in humans," he said. "One day, I thought, 'I should check out what's the closest human homolog of the para gene.' So I did that."

He found a very close match between para and the human gene SCN1A. Subsequently he found that mutations on that gene underlie forms of epilepsy including the childhood forms generalized epilepsy with febrile (fever-triggered) seizures and severe myclonic epilepsy of infancy.

Reenan realized that if he could precisely and reliably create the epilepsy mutations found in the human SCN1A gene in the fruit fly para gene, he'd have a mass producible platform for genetic research into the disease. Fruit flies can be bred, engineered and observed by the thousands, and his flies would be genetically meaningful stand-ins for people.

Now that he's succeeded in making flies that mimic human epilepsy, his goal is to breed and observe the mutant flies in ways that intentionally mutate them further. Maybe one of those mutations will suppress the disease.

A unique technique

The trick, one that the NIH reviewers found to be "exceptional and unconventional" enough to support with the EUREKA gra
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Contact: David Orenstein
david_orenstein@brown.edu
401-863-1862
Brown University
Source:Eurekalert

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