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At the Intersection of Math and Biology, Sindi Lab Sees a Breakthrough in Prion Disease

May 4, 2020
Professor Suzanne Sindi

A UC Merced researcher and her lab have unlocked one of the mysteries that could lead to treatments — or even cures — for prion diseases in mammals.

Prion diseases are a family of rare, progressive neurodegenerative disorders that affect both humans — such as with Creutzfeldt-Jakob disease or fatal familial insomnia — and animals, such as mad-cow disease. These disorders are usually rapidly progressive and always fatal, according to the Centers for Disease Control.

Prions are abnormal, pathogenic, transmissible agents that induce abnormal folding of specific normal cellular proteins called prion proteins, which are found most abundantly in the brain.

But Department of Applied Mathematics Professor Suzanne Sindi and her students have discovered a structural difference between two strains of prions that no one thought existed.

“We’re able to explain previously inconsistent research results through these differences,” Sindi said. “We showed them in yeasts, but then we analyzed the data on human prions, and these differences provide a plausible explanation there, too.”

Sindi’s work is detailed in a new paper in the prestigious journal Nature Structural Molecular Biology.

“Professor Sindi’s discovery is a testament to her creativity and the power of working at the intersections of disciplines, which are fertile ground for novel approaches to solving important problems,” School of Natural Sciences Dean Betsy Dumont said.

Researchers do not know a lot about prion diseases, or even about prions themselves. Even the functions of normal prion proteins are not completely understood, according to the CDC. What is known is that prion diseases affect the nervous system in humans and animals, and in people, impair brain function, and cause rapidly developing dementia, difficulty walking, hallucinations, muscle stiffness, confusion, fatigue and difficulty speaking.

Prion diseases are sometimes spread to humans by infected meat products, though some can also be inherited.

Sindi, a member of the Health Sciences Research Institute, uses yeasts to learn how to take advantage of normal biological systems to reverse the proteins’ aggregate misfolding folding processes.

“If we can understand them in yeasts, it could be incredibly helpful in finding treatments for the human prion diseases,” she said.

Her work is being supported through a Research Project (RO1) Grant from the National Institutes of Health — the original and oldest grant program through the federal agency. It’s rare for an applied math researcher to receive such a grant, as it is still unusual for applied math researchers to turn their focus to health-related matters.

“Getting this award speaks to both the exceptional quality of Suzanne’s research program as well as her effectiveness in working across disciplinary boundaries, bringing advanced mathematical methods to help to solve important problems in biology,” said Professor Mayya Tokman, applied math department chair. “Our department has fostered interdisciplinary research since its beginning and it is good to see that such efforts are paying off by bringing such prestigious awards to applied math faculty.”

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