Federal Project Grant Award Summary

The University of Arizona received a $650,419 Project Grant from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), awarded July 15, 2026, with completion targeted for March 31, 2030. The award funds research to develop a comprehensive mechanistic understanding of sarcomeric protein interactions and their role in hypertrophic cardiomyopathy (HCM). The research extends the investigator's existing program by employing coupled time-resolved fluorescence resonance energy transfer (FRET) computational methods to characterize highly mobile, previously unresolved regions of the cardiac thin filament (CTF), particularly the interactions between the N-terminal of cardiac troponin T (CTNT) and the C-terminal of cardiac troponin I (CTNI) across successive CTF units.

The project deliverables encompass experimental and computational studies investigating how mutations in the CTF and myosin proteins are allosterically transmitted to affect cardiac muscle function in remote regions. Specifically, the research will examine cross-filament unit interactions via dynamic analysis of mobile protein domains, determine the bidirectional effects of myosin mutations on CTF function and vice versa, and extend existing experimental models from myosin S1 to more complete myosin constructs. These research outputs will advance understanding of the molecular mechanisms underlying genetic cardiomyopathies and contribute to the broader NHLBI mission of promoting prevention and treatment of cardiovascular diseases through mechanistic investigation at the molecular and cellular level.