Flies aid study of degenerative brain diseases

BY JOAN TUPPONCE

Most people consider flies of any size or variety to be a nuisance, but Associate Professor of Biology John Warrick sees them as a valuable asset to his research.

Warrick, who has spent much of his career studying brain degenerative diseases, uses tiny fruit flies to help decipher the genetic causes of polyglutamine diseases, which include Huntington’s Disease and Machado-Joseph Disease.

Both Huntington’s and Machado-Joseph are inherited diseases that have adult onset. Currently, there is no treatment or cure for either disease.

“People normally die within 10 years of being diagnosed with Huntington’s or Machado-Joseph,” Warrick says. “If one parent has one of the diseases, you have a 50 percent change of having the disease.”

Fruit flies, according to Warrick, are a great model system to use in the research lab because they have a short life cycle and can be genetically tested in various ways.

“For our purposes, they are better than mice,” he observes.

Warrick recently received a three-year, $182,159 grant from the National Institute of Neurological Disorders and Stroke to identify proteins in brains that are expressing the mutant disease gene and compare them to brains that express the normal gene.

“Normally we look at individual genes, one at a time,” he explained. “This research uses a larger approach where we look at all the genes.”

The brain cells and genes in fruit flies work the same way as the cells and genes in humans.

“At the cellular, molecular and genetic levels, flies are the same as people,” Warrick explains. “Using fruit flies, we can pick out different cellular and molecular pathways and see which ones are active and which are not. Once we understand what pathways they are, we can pick out individual genes and turn them on or turn them off to see if we affect the disease process.”

Warrick’s current research is immediately relative to polyglutamine diseases, but in the future it may be used to study other brain degenerative diseases such as Alzheimer’s.

The fruit flies, which are much smaller than house flies, are easy to care for, making them a good tool for undergraduates. Hersh Gupta, ’10, has been working in Warrick’s lab since his freshman year. “I’m the protein guy,” he says.

Gupta asked to work with the fruit fly study because of his interest in neuroscience and his hope to become a neurosurgeon. “I enjoy studying an actual disease that affects people’s lives,” he explains. “The work that I am doing may possibly contribute to a cure. I like knowing that I’m working toward something.”

Working with Warrick is a pleasure, he adds. “He knows a lot about the subject.”

Warrick began his research during his post-doctoral work at the University of Pennsylvania. He asked to bring the project with him when he came to Richmond in 2002.

“I really wanted to understand how the disease works,” he says. “I’ve always been interested in trying to study relationships between genes and neurons and how they control the brain.”

In the lab, Warrick and his team track the lifespan of fruit flies. Flies will get the disease if they have the mutant gene. “We look at their brains at various stages of progression,” Warrick says. “They live about 75 days in the lab. The ones with the disease will die a lot sooner, 20 to 25 days.”

Anthony Phan, ’11, who started working in Warrick’s lab last summer when he was a pre-freshman, enjoys working with Warrick. “He’s a really nice guy,” Phan says, “This is a relaxing lab.”

Warrick’s lab is the control center for various projects related to the brain. Drew Simmelink, ’11, who is interested in neurodegenerative diseases, is fascinated by Warrick’s work in that field. “His knowledge of those types of diseases is phenomenal,” Simmelink says. “His experience helps you gain more experience.”

The passion that Warrick has in his work carries over into his teaching. He enjoys watching students who are unfamiliar with his research begin to take ownership of their lab projects. “As they start to generate meaningful data, they develop as scientists, and that’s a rewarding experience,” he says.