Project Grant R35GM162377

Federal Project Grant Award Summary

Boston University Medical Campus received a $439,148 Project Grant award dated March 13, 2026, from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859). The five-year award, concluding January 31, 2031, supports fundamental research investigating the regulation of mitochondrial DNA (mtDNA) packaging and gene expression. The research aims to advance understanding of metabolic adaptation and mitochondrial-associated diseases by developing and applying cutting-edge sequencing technologies to elucidate how cells regulate energy production through mtDNA packaging, expression, and replication.

The project builds upon the investigator's previously developed mtFiber-seq methodology, which measures mtDNA accessibility at single-genome resolution, addressing limitations of conventional population-averaging approaches. Key research objectives include determining how mitochondrial gene expression is regulated in response to cellular perturbations, understanding the dual repressor-activator mechanisms of TFAM (the primary mtDNA packaging protein), and elucidating how nucleoids transition between inactive and active states. The research employs both in vivo cell culture systems and in vitro reconstituted nucleoid approaches to advance understanding of fundamental mechanisms governing mitochondrial genome function and energy metabolism regulation.