Department of Molecular and Cellular Biology,
University of Guelph
Pedaling for Parkinson’s New Investigator Award
New Investigator Award: $90,000 over two years
Targeting mitochondrial defects in an isogenic human stem cell model of Parkinson’s Disease
In the quest to discover what’s killing the dopamine-producing cells whose death results in Parkinson’s disease, neuroscientist Scott Ryan is honing in on a group of proteins that turn signalling networks in the brain on and off.
Ryan, an assistant professor at the University of Guelph, concentrates on the balance between cell generation and degeneration, and on finding ways to reverse the latter. Ryan uses a model of Parkinson’s disease derived from sample tissue from a woman with a familial form of Parkinson’s. Once in culture, the donor cells were reprogrammed into stem cells and researchers were able to correct the genetic mutation, in this case a mutation in the alpha-synuclein gene.
Ryan is using this model and system to identify a family of proteins, called transcription factors, in dopamine-producing cells. He describes these proteins – including one called MEF2 – as a “pro-survival team” that can keep the dopamine-producing cells alive.
If disease mutations or environmental contaminants like pesticides or herbicides evoke stress in the energy-producing portions of the cells called mitochondria, the stress can turn off the survival team’s signalling network and block their ability to make more mitochondria.
“The more stress that builds up, the more you deactivate (the proteins) until you reach a critical level, and now the cell has to die,” Ryan explains.
By working with a drug discovery and development group, Ryan hopes to test different compounds on the stem cell model of Parkinson’s disease, to find one that will turn MEF2 and the signalling network he has discovered back on. He hopes his discoveries will apply to both familial forms of Parkinson’s disease – something that runs in his own family – and non-familial, or sporadic, forms.
“It really doesn’t matter why you have Parkinson’s, because what’s defective is common in all forms, at a cellular level,” Ryan says.
Because Ryan’s work involves a model made from real human cells with Parkinson’s disease, his discoveries will be easier to move into drugs that treat humans eventually, compared with animal models of drug discovery, he believes. “Translating it to humans will be less of an issue,” he predicts.