Federal Project Grant Award Summary

The National Institute of General Medical Sciences (NIGMS) awarded The Salk Institute for Biological Studies a Project Grant of $625,589 (awarded July 10, 2026; completion March 31, 2030) under the Biomedical Research and Research Training program (CFDA 93.859) to investigate the molecular determinants regulating cohesin-mediated loop extrusion and chromatin stability in living cells. The research addresses a critical gap in understanding three-dimensional genome organization by moving beyond in vitro observations to directly measure loop extrusion dynamics in vivo. The project will employ novel tools and approaches to characterize how cohesin and associated factors dynamically regulate chromatin loop formation, duration, and stability at the megabase level—processes essential for regulating gene expression, DNA replication, and DNA repair.

Specific research activities include determining molecular factors contributing to loop duration through analysis of cells lacking the cohesin subunit NIPBL, with the goal of identifying locus-specific regulators of loop extrusion rates and persistence on chromatin. Preliminary data indicates heterogeneity in loop dynamics across genomic loci, suggesting that loop extrusion in vivo is a regulated process distinct from in vitro observations. By elucidating the regulatory mechanisms governing chromatin looping in living cells, this research will advance fundamental understanding of how dynamic three-dimensional genome architecture controls nuclear processes and may inform therapeutic approaches targeting chromatin structure-dependent cellular functions.