Paul Marcogliese, University of Ottawa
Graduate Student Award: $30,000 over two years

Mutations in the Parkinson’s disease-related gene LRRK2 cause autophagic deficits, which are mediated by a SNARE-dependant mechanism.

A gene called LRRK2 is the most commonly mutated gene linked to familial Parkinson’s disease. But researchers still don’t know exactly what LRRK2 does and how precisely it operates within cells.
At the University of Ottawa, neuroscientist Paul Marcogliese, a doctoral candidate, is trying to answer those questions through his work with fruit flies.

Since fruit flies share about 70 per cent of the same proteins as humans, they’re a good model for this kind of basic research. Marcogliese believes LRRK2 is involved in the process within a cell that “recycles” damaged proteins, preventing cell death. People with Parkinson’s disease have clumps of misfolded, or misshaped, proteins in their brains – proteins that should have been degraded by the cell recycling system. If LRRK2 is defective, it may be part of the reason the recycling process doesn’t work. Marcogliese is testing LRRK2’s interaction with other genes and proteins associated with the recycling process, to determine exactly LRRK2’s function within the process.

“If we can find out what it’s doing in the cell, then we can look at making therapeutics (drugs or other treatments) to either help out with whatever it is not doing, or stop it from doing it’s bad thing when it is mutated,” Marcogliese explains.

Once Marcogliese and his colleagues determine what combination of proteins and genes associated with LRRK2 either prevent or precipitate cell death, they can move on to testing the process in a mouse model of Parkinson’s disease.

Marcogliese originally wanted to be a forensics specialist. But when he volunteered in the laboratory of neuroscientist David Park, to get lab experience, he met and worked with a teacher with early-onset Parkinson’s disease who is raising awareness about Parkinson’s disease and funds for research.

“She’s a really inspirational individual,” Marcogliese says of Shelby Hayter. Marcogliese’s association with Hayter and his admiration for actor and Parkinson’s activist Michael J. Fox combined to change Marcogliese’s mind and turn him towards a research career working on Parkinson’s disease. “I find the evolutionary mechanisms of biology extremely interesting as well,” he says.