Fruit fly genes yielding clues to a deadly disease

As this was happening, scientists who study other brain diseases were making progress.

At Penn, the prominent husband-and-wife research team of Virginia Lee and John Trojanowski found a new clue about a type of dementia: the brain cells of patients were marked by unnatural clumps of a protein called TDP-43.

And the same clumps were found in people with Lou Gehrig's disease.

Other researchers checked brain samples from people who had died of IBMPFD - the disease Taylor and Ritson were studying in the flies - and sure enough, there was abnormal TDP-43.

Taylor was energized. "We knew we were on the same biological pathway," he said.

Most of these neurodegenerative diseases are marked by abnormal buildup of some protein. But it isn't always clear whether the clumps actually cause the disease or are merely a telltale sign.

So Ritson needed to identify a few of the individual genes from her 74 chunks, and find out what they did. With Taylor's guidance, she picked a few hits that looked interesting - including the section containing the gene with the recipe for TDP-43. She set out to check the genes in those sections one by one.

She ordered more custom flies, this time from a facility in Vienna that can silence individual genes with a new technique called RNA interference. Once again she bred flies, mating the Vienna insects with the diseased flies, to see which individual genes would, when silenced, make a difference.

The result was a paper in the Journal of Neuroscience, by Ritson, Taylor, and a slew of others, including Penn's Lee and Trojanowski.

They identified three genes that had an impact on the disease, the one that lays waste to brain, muscle, and bone.

One was indeed the gene with the recipe for TDP-43 - indicating that abnormal clumps of this protein were not just a mark of the disease, but a driver of it.

In healthy people, molecules of this protein spend most of their time in the nucleus of brain cells. But in those afflicted, the protein builds up in the cell's cytoplasm. And the authors reported that the very same thing was happening in their tiny insects.

Taylor is so keen on this avenue of research that he now has four or five people on it.

Kimonis, who identified the disease in 2000, praised the paper. "They are competitors, but they move the science forward," she said. "Paul Taylor is a fantastic researcher."

Both continue to work on this disease, as do a few others. Someday they aim to find a treatment, finding the right point to intervene in the fatal genetic cascade.

Ritson, meanwhile, is starting to look for a postdoctoral fellowship.

She defends her Ph.D. next month.

Contact staff writer Tom Avril at 215-854-2430 or tavril@phillynews.com