Federal Project Grant Award Summary

The University of Chicago received a $602,095 Project Grant from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859), effective July 1, 2026, through June 30, 2031. This five-year award supports fundamental research investigating the structural and functional mechanisms of macromolecular complexes involved in protein and RNA modifications. The research focuses on three interconnected biological systems: the ubiquitin-proteasome pathway for protein quality control, vault particles housing the ADP-ribosyltransferase PARP4 (poly(ADP-ribose) polymerase 4), and RNA modifications including m6A and m5C that regulate gene expression and chromatin interactions.

The deliverables encompass original scientific research combining structural biology, chemical biology, proteomics, and cell-based assays to elucidate substrate recognition mechanisms, catalytic processes, and downstream regulatory effects. Specific research objectives include defining how atypical ubiquitin linkages and the AAA+ ATPase (adenosine triphosphatase) CDC48 (also known as p97) drive proteome remodeling under stress, characterizing substrate recognition by UBR-box-containing E3 ligases in the N-degron pathway, uncovering PARP4-mediated ADP-ribosylation mechanisms within vault particles, and resolving the structural basis of RNA modification specificity and its chromatin regulation interactions. Research outcomes will integrate biochemical reconstitution, high-resolution imaging, and cellular perturbation studies to establish foundational principles governing macromolecular signaling processes.