Federal Grant Award Summary

The National Institute of General Medical Sciences (NIGMS) awarded The Johns Hopkins University a $334,325 Project Grant (CFDA 93.859: Biomedical Research and Research Training) effective July 1, 2026 through April 30, 2030 to conduct fundamental research on the structural and biochemical mechanisms of histone H2A.Z exchange mediated by the human SRCAP chromatin remodeling complex. The research addresses critical gaps in understanding how SRCAP selectively incorporates the histone variant H2A.Z into nucleosomes at promoters, enhancers, and insulators—a process dysregulated in cancers and developmental disorders. The project will deliver high-resolution structural data using cryo-electron microscopy (cryo-EM), biochemical characterization of substrate specificity, and systematic analysis of how histone post-translational modifications regulate SRCAP activity in coordination with the TIP60 histone acetyltransferase complex.

The research integrates multiple experimental approaches including cryo-EM imaging, biochemical assays, single-molecule TIRF imaging, and high-throughput profiling to elucidate how SRCAP senses nucleosomal features and coordinates with acetylation machinery. Expected deliverables include high-resolution structures of SRCAP-nucleosome complexes, comprehensive characterization of post-translational modification effects on binding and exchange dynamics, and mechanistic insights into chromatin dynamics that will inform understanding of chromatin-related diseases and gene regulation. The work is conducted at The Johns Hopkins University in Baltimore, Maryland.