Prof’s research sheds light on prion disease

By
Wednesday, January 31, 2007

Tricia Serio, assistant professor of medical science, and her lab are researching proteins in an effort to understand what causes specific types of genetic diseases, such as mad cow disease, Creutzfeldt-Jakob disease and kuru. Known as progressive neurodegenerative diseases, these genetic diseases are caused by proteins called prions and are currently untreatable.

Prion is short for “proteinaceous infectious particle,” a protein that acts an infectious agent. Prions affect the structure of neural tissue, impairing bodily functions and propagating by converting normal proteins.

Until recently, it was not clear how the prions were able to change the conformation of normal proteins. But Serio, Prasanna Satpute-Krishnan GS and Serio’s lab were able to prove a longstanding theory that prions immediately deform regular proteins when they come into contact with them. The team first published their findings in Nature magazine in 2005. Less than two years later, Serio and her team published new research that could lead to a cure for prion diseases.

In a Jan. 23 edition of the online open-access journal PLoS, short for Public Library of Science, Serio and her team revealed that they have identified the protein that breaks down insoluble prion aggregates and allows them to spread and cause disease.

When these aggregates break down, many small “seeds” form, and around them, clumps of prions. The prions spread rapidly, so the presence of only a few prions can still cause major health problems.

Serio and her team researched prion formation in yeast and identified HSP104, a member of a large family of heat-shock proteins that are present in all cells, as the agent responsible for breaking down the aggregates. Because heat-shock proteins are present in all living things, the lab’s research is relevant for humans as well.

In their research, Serio and her lab used fluorescent tagging to identify the role of HSP104 in prion disease. “We showed direct proof that HSP fragmented the aggregates,” Serio said.

The implications of Serio lab’s latest findings are significant beyond expanding knowledge about prions. Further research on the role of HSPs could result in advances or even cures for prion-based progressive neurodegenerative diseases.

But Serio and her lab are not planning to explore the practical applications of their research. Instead, they will focus on further understanding the nature and mechanisms of prion propagation.

“We want to understand it as a process, understand how it works,” Serio said.

Serio said she has been interested in prions for several years. “As an undergraduate at Lehigh, a post-doc told me about infectious protein. I thought he was joking at first,” she said. “Ever since then I’ve been interested in it.”

After graduate work at Yale University and post-doc research at the University of Chicago, Serio said she is pleased to be doing research at Brown.

“Brown is a really great place to work,” she said. “The students in particular are very intelligent and helpful.”