Federal Grant Award Summary

The University of Arizona received a $1.89 million Project Grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) under the Arthritis, Musculoskeletal and Skin Diseases Research program (CFDA 93.846), effective July 1, 2026, through June 30, 2029. The award funds research investigating the molecular mechanisms underlying nebulin-associated congenital myopathies, specifically focusing on a novel class of dominant nebulin variants characterized by large in-frame deletions. The project will produce research deliverables including quantitative analyses of patient biopsy-derived RNA and protein levels, ribosome profiling (RIBO-SEQ) data assessing translational output, structural microscopy imaging using STORM microscopy technology, and contractile assay results examining functional impacts of mutant nebulin protein in muscle tissue.

The research encompasses two primary investigative aims designed to elucidate disease mechanisms and protein dynamics. Aim 1 will deliver comparative analyses of transcript abundance and translation efficiency in patient samples, while Aim 2 will produce in vivo fluorescence recovery data and nebulin turnover kinetics measurements using novel Dendra2-tagged mouse models with surgically implanted imaging windows. These research activities will advance understanding of how altered translation efficiency and accelerated replacement kinetics of truncated nebulin contribute to myopathy development, with findings anticipated to inform future therapeutic development for this musculoskeletal disorder.