Gamma Ray Blast May Help Huntington's Disease Therapy

UAH students and faculty are working with the Army's Primary Standards Laboratory at Redstone Arsenal and several tiny worms (who didn't always glow in the dark) to search for clues that might lead to new therapies for Huntington's disease.

"This line of research is definitely worth pursuing," said Dr. Lynn Boyd, an associate professor of biology at UAH. "It's still too early to say whether anything therapeutic might come from this, but it is … promising."

Using generations of tiny C. elegans nematode worms descended from ancestors who were genetically tagged in the Army's gamma ray chamber, Boyd and her student assistants are trying to learn what effects different enzymes have on clumps of amino acids associated with Huntington's disease.

It isn't known whether these aggregates of polyglutamine are good or bad. Although the clumps are large compared to the cells — proportionally, they can take up as much space in a cell as a seven-inch tumor in an average man — some scientists believe they might be a cell's way of taking bad amino acids out of circulation by collecting them in one place.

Good or bad, the UAH team has found some enzymes that make the clumps bigger and some that make them smaller.

They study the enzymes, which are found naturally in the clumps, by tagging the worm's chromosomes with proteins or enzymes attached to glowing proteins (which are harvested from jellyfish and other fluorescent beasties). They inject the dye-tagged genetic material into the worms before they are zapped by powerful radiation.

At just the right level of radiation, the DNA strands in the worms' unfertilized eggs snap and the dye-tagged material slips into the chromosomes while the worm isn't looking. The glowing protein is then reproduced in the worm's offspring. If the target material concentrates in clumps it creates glowing spots, giving the UAH researchers a tool for tracking what happens when specific enzymes are suppressed.

In a recent trip to the Army's radiation lab, the UAH team hoped to tag individual strains of worms for seven specific enzymes.

"One of the best things about the Army lab is that they are so meticulous," said Boyd. "We always get exactly the right dose of radiation, which might be why we've had a one hundred percent success rate so far."

Boyd and her team think they might have had another successful zapping in February, although they can't be sure until they see the great-grand eggs of the worms that were irradiated. That should happen any time now, since C. elegans goes from hatching to parenthood in about three days.

"It's always interesting when Lynn brings her worms out," said Steve Rogers, a senior physicist in the Wynn center's nucleonics lab. "We appreciate the opportunity to contribute to a research project like this one."

Using human cells grown in a culture, Boyd found that suppressing the human enzymes that corresponded to the worm enzymes had the same effects on polyglutamine aggregates. Now she is talking to colleagues at The University of Alabama at Birmingham about taking this research to the next level.