Federal Grant Award Summary

The University of Rochester received a $427,227 Project Grant award from the National Institute of General Medical Sciences under the Biomedical Research and Research Training program (CFDA 93.859), effective March 1, 2026 through December 31, 2030. This award supports fundamental research investigating the mechanisms of action of gene-regulatory riboswitches—naturally occurring RNA molecules that sense metabolites and ions to control gene expression in bacterial cells. The research employs high-resolution structural approaches and in-cell methods to elucidate how intact riboswitches function, with particular focus on characterizing previously uncharacterized "Class X" and "Class Y" riboswitches that sense key metabolites and monovalent ions.

The deliverables under this award include structural elucidation of unknown riboswitch architectures, molecular characterization of ligand-specificity mechanisms, and functional analysis of riboswitch conformations relevant to cellular processes. Preliminary findings on the Class Y spermidine riboswitch have revealed dual ligand binding with positive cooperativity and enhanced binding through K-turn protein interactions. The research outcomes will contribute foundational knowledge of RNA-based cellular regulation, with potential implications for RNA-targeted therapeutics development.