Federal Project Grant Award Summary

The University of Nevada, Las Vegas (UNLV) received a $411,739 Project Grant from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859), awarded on May 21, 2026, with an ultimate completion date of February 28, 2031. This research initiative focuses on elucidating the cullin-ring ligase (CRL) code—a fundamental molecular mechanism involving ubiquitin ligases, which represent approximately half of all human ubiquitin ligases and play critical roles in protein degradation and drug discovery through the targeted protein degradation platform. The research project employs advanced methodologies including single-molecule fluorescence resonance energy transfer microscopy, cryo-electron microscopy, high-resolution kinetics analysis, proteomics, and cell biology techniques to characterize how CRL subunits interact with ubiquitin-carrying enzymes during substrate selection and ubiquitylation.

The project deliverables encompass fundamental research outputs aimed at uncovering the specificity code governing CRL-ubiquitin enzyme interactions, with particular focus on characterizing CRL dynamics and the RBX1/2 subunit's role in recognizing ubiquitin-carrying enzymes. Through structural and kinetic studies, the research will elucidate mechanisms of complex formation stabilization and direct interactions between ubiquitin-carrying enzymes and CRL substrate receptors. These research findings will advance understanding of protein degradation pathways and provide foundational knowledge supporting the development of targeted protein degradation therapeutics and drug discovery applications.