Northwestern University Receives $12.6 Million to Study Protein Balance Mechanisms in Health and Disease

The National Institute on Aging at the National Institutes of Health (NIH) has granted $12.6 million to Northwestern University to study the role of protein quality control mechanisms in human aging and neurodegenerative diseases, including Huntington’s.

The five-year grant is one of the NIH’s Program Project Grants, designed to assemble exceptional researchers to solve unique problems that help to better understand aging and the risk for age-associated diseases.

The team will be led by Northwestern’s Richard I. Morimoto, who is the Bill and Gayle Cook professor of biology and director of the Rice Institute for Biomedical Research in Northwestern’s Weinberg College of Arts and Sciences. The team also will include:

• Steve Finkbeiner of the University of California, San Francisco, who is an expert on the mechanism that cells use to destroy and recycle proteins and other cellular components, so-called autophagy, and live-cell imaging of patient-derived nerve cells;
• Daniel Finley of Harvard Medical School, who is an expert on protein clearance processes;
• Judith Frydman of Stanford University, an expert on molecular chaperones known to be important mediators in the protein folding mechanism, and;
• Jeffery Kelly of The Scripps Research Institute, an expert in chemical biology.

The proposed project will use genetically modified yeast and worm models, as well as mouse models and patient-derived brain cells, to identify molecular alterations that may help explain and predict what changes during aging, at the cellular and molecular levels, that puts older people at risk for neurodegenerative diseases and age-related disorders.

This broad approach is expected to provide new insights and help identify potential targets that could represent new therapeutic avenues for the treatment of several human diseases, namely Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), and Huntington’s disease.

“We have the ‘A-team’ on the mechanisms of protein quality control,” Morimoto said in a university press release written by Megan Fellman. “Together we can accomplish much more than a single lab could achieve.”

“As humans age, quality control of proteins declines,” he said. “Our goal is to understand both how the cellular machinery functions in health and also how it fails in aging, increasing the risk for protein misfolding, aggregation, and proteotoxicity. A priority will be to develop successful small molecule strategies to prevent and restore proteostasis [protein correct balance] in neurodegenerative diseases.”

The team, which will be known as the Proteostasis Institute, will work as an integrated and interdependent research team distributed within the five involved institutions.

Researchers also will provide laboratory cross-training for graduate students and postdoctoral fellows, and sponsor an annual symposium on aging and neurodegenerative diseases.