Department of Cellular and Molecular Medicine,
University of Ottawa
Pilot Project Grant: $45,000
Role of DJ-1 in regulation of Autophagy
David Park, a professor at the University of Ottawa, deals with an extremely subtle, but extremely important aspect of how Parkinson’s disease develops. He examines a process called autophagy, which governs the way our body’s cells dispose of waste products – much like a recycling process.
“Autophagy obeys the Goldilocks rule,” he explains. “Too much is not good, and too little is not good. It has to be just right, which is what makes this research so challenging.”
In other words, when autophagy is operating appropriately, our cells recycle dead or damaged material at the right time, without discarding their healthy components. A number of proteins appear to contribute to striking this balance. Park’s attention was captured by proteins controlling a gene called DJ-1, which is linked to the loss of brain cells that produce dopamine, a primary hallmark of Parkinson’s disease. If DJ-1 or other genes and their proteins involved in the recycling process are mutated, waste materials in dopamine-producing cells can pile up, killing those cells.
“It’s a shockingly multifaceted disease where a lot of things go wrong, things that affect the quality of life beyond the central issue, which is movement dysfunction,” Park says.
Park’s research examines the function of various proteins that interact with DJ-1, in order to identify those that change its function in ways that influence autophagy. If he can decipher the role of these proteins, it could lead to a treatment that keeps the recycling process going and brain cells alive. Ultimately, that could slow down the progress of Parkinson’s disease – or even prevent it.
The sheer complexity of this devastating problem appeals to Park’s scientific curiosity. “The more complex it is, the more intriguing it gets,” he confesses. “For me it poses a consistent challenge.”
Nevertheless, he remains conscious of the fact that there is much more at stake than solving a puzzle about how the body’s organization breaks down.
“Having been this field for a long time, I now know many people with Parkinson’s,” he observes. “I do this work with them in mind all the time.”