September 04, 2019
The “misfolded proteins,” cause neurodegenerative diseases in humans and many other animals. With new National Institutes of Health funding, Dale Cameron will continue his investigation into what triggers prion formation.
Prions are proteins that are twisted and folded into “alternative conformations.”
“Once a protein switches into a prion conformation, it can rapidly propagate its shape to virtually all other copies of the same protein,” says Cameron, an associate professor of biology.
In humans and other mammalian species, the propagation of altered protein conformations is associated with mad cow disease, scrapie in sheep and chronic wasting disease in deer and elk, among other diseases.
“Even Alzheimer’s and Parkinson’s share many similarities with prion diseases in that they result from the propagation of these misfolded protein conformations,” Cameron says.
To get to the bottom of what causes the alternative conformations, Cameron works with yeast cells, a versatile model system because it shares a lot of similarities with human cells. “Many yeast genes have human counterparts,” he says, “so, when we study yeast, we’re learning about how many kinds of cells work, including our own.”
In yeast, prion formation is triggered when a cell experiences stress. But in many instances, prion formation has been known to help the cells survive the stress, “which is really different than what we’re used to thinking about in humans,” Cameron says.
“It seems like prion formation might actually be part of a broader, more fundamental biological mechanism for propagating these altered cellular states—and it could be good, or it could be bad,” he says. “We’re interested in understating more about how prion formation is induced, what triggers it, how it’s induced by stress, and the physiological consequences of prion formation.”
Cameron has been working in this field since he was a post-doctoral researcher at the University of California San Francisco and is continuing the research in his Thomas Hall lab alongside Ursinus student researchers and research assistant Dr. Christina Kelly.
“We’re looking at different quality control systems within the cells, and those systems help make sure the proteins stay in the right shape,” he says, and he’s published a research paper that shows that the absence of those quality control factors can influence how frequently prions form.
Now, Cameron and his researchers introduce cells to stressors like heat or nutrient limitation so they can measure the frequency by which prions are forming as a result. His team also looks at the human counterparts of yeast quality control factors to understand if they work in the same manner in humans.
Most of the work in this field is done at large research institutions, Cameron says, making the NIH funding and the opportunity for Ursinus undergraduates to participate in the research even more significant.
“It’s helping to train the next generation of scientists,” Cameron says. “Having an experience like this is really instrumental in preparing them for grad school.”