Federal Grant Award Summary

The Salk Institute for Biological Studies received a $122,763 Project Grant from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859), awarded February 1, 2026, with completion targeted for January 31, 2028. This award supports fundamental basic research investigating the structural and functional mechanisms of nuclear receptors—specifically retinoic acid receptor-related orphan receptor gamma isoform 2 (RORγt) and glucocorticoid receptor (GR)—and their interaction with chromatin during gene regulation. The research deliverables include structural biology studies utilizing chromatin biochemistry and cryo-electron microscopy techniques to determine how these nuclear receptors bind to nucleosomes and recruit coregulatory protein complexes, with particular focus on elucidating histone acetylation mechanisms in target gene activation.

The project builds upon preliminary findings demonstrating that DNA response element positioning on nucleosomes influences RORγt and GR engagement with chromatin. Key research outputs will involve solving full-length protein structures of coregulatory proteins SRC3 and P300 in complex with RORγt, advancing mechanistic understanding beyond previous peptide fragment-based studies. These investigations are designed to enhance knowledge of how nuclear receptors—major drug targets in the immune system—function at the molecular level, ultimately supporting development of improved therapeutic interventions.