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Stanford researchers to participate in new Center for Protein Folding Machinery

It is one of four multi-institution research centers created by NIH to find new ways of curing disease on molecular scale

Judith Frydman

Judith Frydman

BY KRISTA ZALA

The National Institutes of Health (NIH) has awarded funding to Stanford University and five other institutions to establish the Center for Protein Folding Machinery.

Judith Frydman, associate professor of biological sciences at Stanford, will serve as co-director of the center along with Wah Chiu, professor of biochemistry and molecular biology at Baylor College of Medicine in Houston.

The scientific mission of the center is to understand how proteins called chaperones work to shepherd other proteins through their intricate three-dimensional folding process. "Misfolded proteins seem to be at the heart of neurodegenerative diseases," Frydman says. Understanding how proteins fold can provide clues in treating a wide range of diseases, including Alzheimer's and cancer, she adds.

In addition to Stanford and Baylor, the center also includes researchers from the Massachusetts Institute of Technology, Lawrence Berkeley National Laboratory, the University of California-San Francisco and the University of Texas M.D. Anderson Cancer Center in Houston.

The center is one of four multi-institution research centers created to study nanoscale medicine under NIH's Roadmap Initiative for Medical Research, which funds research for new ways of curing disease or repairing damaged tissues on a molecular scale. The four NIH centers will share approximately $42 million over five years.

Four other Stanford researchers with expertise in nanoscale research also will participate: computational biologist Michael Levitt, professor and chair of the Department of Structural Biology; biophysicist and structural biologist Vijay Pande, assistant professor of chemistry; W. E. Moerner, the Harry S. Mosher Professor of Chemistry, who specializes in single-molecule science; and biomechanics expert Scott Delp, professor of bioengineering and of mechanical engineering, who chairs the Bioengineering Department.

"To understand these biological nanomachines, you have to marry all these different techniques," Frydman says. "It's an opportunity to understand each other's language and build from each other's strengths."

Protein chaperones

A protein—such as hemoglobin in blood—is spat out as a string of amino acids from an RNA template fed into enzymes called ribosomes. Even a protein with all the right amino acids in all the right places needs help twisting and folding to the right shape. And that's where protein chaperones come into play, crimping and tucking a simple chain into its functional 3-D structure.

"First it was thought that proteins folded spontaneously," Frydman says. "Then it became apparent that … many medically relevant proteins are dependent on the help of chaperones to fold."

Recent work already has uncovered links between chaperone-guided protein folding and several types of cancer, as well as cardiovascular disease and Alzheimer's, Parkinson's and Huntington's diseases. "Protein misfolds can actually be toxic," Pande notes. "In Alzheimer's, it's a misfolded and aggregated protein that leads to neurodegeneration and the symptoms you see in Alzheimer's patients."

Nanomedicine is such a young field that candidates were asked to define it in their center proposals. "It ranges from the study of molecular motors to, in our case, a folding machine, a specialized biological container," Moerner explains. "Others were looking at motors, at enzymes, at different biological systems that some might regard as a nanoscale object that's doing something important."

By understanding the physical and engineering principles of how proteins are folded correctly, researchers may one day be able to determine how the process goes wrong and engineer a new chaperone to correct the mistakes.

"Typically, with a proposal that's driven by one professor, everyone works for one particular project," Pande says. "By working together we'll do something that none of us could do on our own."

Krista Zala is a science-writing intern at Stanford News Service.