Highlighting Eberly research on Parkinson’s disease
Because April is Parkinson’s Awareness Month, we’re featuring two Eberly researchers who are studying this disease from two very different angles.
Daisy Philtron
Daisy Philtron, assistant research professor of statistics, is building a framework to study diseases that incorporates different types of data at the same time. She is currently using the framework to study Parkinson’s disease, but the framework is flexible and can be used with data from any kind of disease that has similar outcomes.
“It’s almost like having an analysis ecosystem where you can add one kind of genetic data, add some survival data, add some family tree data from families that have Parkinson’s, and then use whatever data you have available to do a larger classification of which genes are linked to the disease,” Philtron said.
Information can be fed into the model from genome-wide association studies and RNA sequencing. Genome-wide association studies include a large set of people, some of whom have Parkinson’s and some of whom do not. Philtron factors in how similar a person’s gene is to those from other people, and then tries to associate each of those signals with whether Parkinson’s is present.
The model then gives Philtron the probability of whether a gene can be helpful or harmful. In families where Parkinson’s is prevalent, she looks for genes that could help delay the onset of symptoms. Once those genes are identified, they can be studied to determine whether they create proteins or contain a biological mechanism that a medication or treatment could replicate.
Scott Selleck
Scott Selleck, professor of biochemistry and molecular biology, studies the processes of neurodegeneration and how cells respond to stress and counteract cellular damage that takes place over a person’s lifetime. Selleck has a personal connection to his research: His mother had Lewy body dementia, a form of Parkinson’s disease.
Selleck’s team studies a class of cell surface molecules that regulate a vital step in protecting cells from damage. That process is called autophagy, which literally means self-eating. Autophagy is involved in removing damaged mitochondria and protein aggregates, which are the two trademarks of neurodegenerative diseases. Selleck found that these surface molecules play an important part in regulating the stress mechanism that is central to cells preventing damage from occurring.
Selleck’s team noticed that when they changed the function of these cell surface molecules, they also changed the levels of autophagy in cells. They realized they could manipulate the level of the cell repair system in a manner that protects neurons from damage in patients with Parkinson’s or even amyotrophic lateral sclerosis (ALS), a nervous system disease that affects motor function.
Using the genetic model of Parkinson’s in fruit flies, Selleck’s team has successfully manipulated the structure of the cell surface molecules to essentially prevent all the damage that occurs from mutation of the Parkin gene, which leads to Parkinson’s.
But why use fruit flies?
“When you can work on an organism that goes from egg to adult in ten days, that’s a big plus,” Selleck said.
Selleck has been working with fruit flies, which share many fundamental biological events with humans, since he was a postdoctoral fellow at the Massachusetts Institute of Technology. In humans, mutation of the Parkin gene causes early onset neurodegeneration, which leads to Parkinson’s; in fruit flies, that mutation leads to neuronal cell death. In both species, the mutations disrupt fundamental processes of how cells deal with damage.
“We discovered a class of molecules that normally serve to inhibit the levels of autophagy,” Selleck said. “When we alter their function, we get a boost in autophagy and that boost is protective. It’s protective for models of Alzheimer’s, ALS, and it’s strikingly effective in Parkinson’s models.”