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Focus on Research: Fly Diets Leading to Disorder Discovery

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This article, written by Barbara Kennedy and featuring the research of Penn State scientist Scott Selleck, originally appeared in the Centre Daily Times (CDT) on 10 June 2012 in the bimonthly "Focus on Research" column, which highlights different research projects being conducted at Penn State.

10 June 2012
Green x-ray like image in shape of a hexagon on black background.

This microscopic image, taken with a fluorescent microscope, of the body-wall muscles of a fruit fly larva helps scientists in Scott Selleck's lab study the development and function of the nervous system, including the fruit fly equivalent of human genes associated with autism spectrum disorder, epilepsy and schizophrenia.

Flies on a calorie-restricted diet have taught Penn State scientists something new that might one day help children with neurological and behavioral diseases like epilepsy and autism. Scott Selleck, the head of Penn State’s department of biochemistry and molecular biology, thinks his lab team could one day control the effect of a genetic defect.

Selleck — a father of five himself — wondered if the rising rates of obesity in children, and their higher-calorie diets, might be linked to the rising rates of neurological and behavioral diseases that involve complicated systems of defective genes.Selleck’s lab recently showed that a low-calorie diet dramatically improved nervous system functioning in the flies that his team engineered to have the genetic equivalent of a childhood disorder. Children with the disorder — tuberous sclerosis — have symptoms that are often diagnosed as epilepsy, attention deficit disorder, hyperactivity or autism.

In children, the genes affect growth-signaling systems, and the child often has benign tumors. Earlier work in Selleck’s lab showed that abnormalities in this critical system also influenced nerve cell development.

“We also know that nutrition regulates this growth-signaling system,” Selleck said.

Past clinical studies have also shown that a restricted-calorie diet could lessen the severity of seizure disorders. But Selleck’s experiments with fruit flies are the first to indicate that diet restriction can benefit the nervous system.

Purple and green ribbon-like streaks against black background.

This microscopic image shows nerve cells (green threadlike structures) on the surface of a fly’s muscle, where the receptors for chemicals produced by the cells are shown in purple. This is the same signaling system used by nerve cells in the brains of animals with backbones, including humans. Scott Selleck’s lab is studying how genes and diet affect the development of nerve cells.

You don’t want to go experimenting with a person’s genes, but Selleck says the fruit fly is a great “model organism” to use for research into the nervous system. He said the fruit fly has “a rich repertoire of behaviors, a reasonably complicated nervous system, about half the genetic complexity of a human being, and the longest tradition of molecular genetics research of any organism in history.” Plus, flies are inexpensive.

Selleck and others have identified about 300 genes that are associated with autism spectrum disorders. Because many of these genes are essentially the same in fruit flies as in humans, scientists can use the flies as a living nervous-system laboratory.

While it is hard to measure a human neurological problem by the behavior of a fruit fly, Selleck found that his tuberous sclerosis flies did have a neurological problem that could be measured. These flies did not move toward light in the same enthusiastic way as do normal fruit flies, indicating that the genetic defect may have affected their vision.

Selleck said he was startled to discover that providing less energy to the defective gene complex by cutting 30 percent of the calories during the flies’ development resulted in dramatic improvement. After treatment, these flies moved toward light just like normal flies. Selleck also found in the brains of these flies fewer defective photoreceptors going the wrong way.

“We were astonished to learn that diet alone can have such a profound effect on neural development,” Selleck said. “We now want to learn how every gene implicated in autism from human genetics research affects the development and functioning of the nervous system in our fruit-fly model and how environment modifies those effects.” One of the goals of Selleck’s research group is to understand how the symptoms of inherited neurological diseases might be improved by changes in diet and other factors in a child’s environment. Selleck’s research could to point the way to the most promising approaches for clinical trials with patients. By helping to decrease the severity of disease symptoms, this research effort could make a huge difference, both emotionally and financially, in the lives of affected children and their families.

Barbara Kennedy is a science writer in Penn State’s Eberly College of Science.

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