Project Grant R35GM162573

Federal Grant Award Summary

The University of Chicago received a $470,385 Project Grant (R35) award from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859), effective April 1, 2026, with completion targeted for January 31, 2031. This award supports investigator-initiated biomedical research focused on elucidating the structure and function of human amyloid-peptide degrading proteases, specifically Presequence Protease (PREP) and Angiotensin-1 Converting Enzyme (ACE). The research aims to advance understanding of how these enzymes degrade monomeric amyloid peptides and prevent the formation of toxic aggregates associated with Alzheimer's disease, Parkinson's disease, and systemic amyloidoses.

The primary deliverable is fundamental scientific research designed to clarify the substrate selection mechanisms and coordinated domain motions utilized by PREP and ACE in capturing and degrading amyloid substrates. By developing a deeper understanding of how these proteases function at the structural and biochemical level, the project may enable the development of improved therapeutic interventions with reduced off-target effects compared to current global protease inhibitors. The research will be conducted at the University of Chicago's facilities in Chicago, Illinois, leveraging the institution's demonstrated capabilities in structural biology and biomedical research.