Scientists from Washington University in St. Louis and St. Jude Children’s Research Hospital have been awarded a five-year $3.1 million grant from the National Institute of Neurological Disorders and Stroke, an affiliate of the National Institutes of Health (NIH).
Rohit Pappu, the Edwin H. Murty Professor of Engineering in the Department of Biomedical Engineering in the McKelvey School of Engineering at Washington University, and Tanja Mittag, of the St. Jude Department of Structural Biology, received the funds to study RNA-binding proteins that are mutated in patients with familial forms of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease.
The goal is to uncover the mechanisms underlying the formation of solid inclusions of these RNA-binding proteins and to enable future identification of new therapeutics for ALS and other neurodegenerative diseases.
“This is an exciting opportunity to work together and build on efforts that were catalyzed by the St. Jude Research Collaborative,” Pappu said. “Our focus is on key components of stress granules and the impact of ALS associated mutations on hitherto underappreciated aspects of pathology that are tied to arrested dynamics of proteins within stress granules. Being able to modulate these dynamics would be a novel therapeutic strategy in ALS and other neurodegenerative disorders.”
The grant-funded research builds on previous WashU-St. Jude collaborative work demonstrating that stress granules in cells form via liquid-liquid phase separation of RNA-binding proteins.
“Phase separation promotes the formation of solid protein aggregates, but why this is the case is unclear,” Mittag said. “Our new work into the underlying mechanisms will help to direct the future development of new therapeutics.”
Work that led to this award was funded by the St. Jude Research Collaborative on Membraneless Organelles. The collaborative brings together investigators at St. Jude, Washington University in St. Louis and Princeton University to accelerate progress in this field. It is one of five St. Jude Research Collaboratives developed to bring together scientists from the world’s top research programs to tackle the still-unknown.
With a goal of speeding advances, the St. Jude Research Collaboratives are addressing significant gaps in knowledge for pediatric cancers, non-malignant hematological diseases and other life-threatening disorders of childhood.
“Collaboration is key to innovation when it comes to solving the complex problems we are working to unravel,” said Charles Roberts, MD, PhD, executive vice president, director of the St. Jude Comprehensive Cancer Center and administrative leader of the St. Jude Research Collaboratives. “St. Jude has made a considerable investment to bring world-leading researchers together to answer some of biomedical science’s biggest questions collaboratively.”