Federal Project Grant Award Summary

The California Institute of Technology received a $1.87M Project Grant from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859), effective March 1, 2026 through February 28, 2030. The award supports fundamental research to elucidate the molecular mechanisms underlying the mammalian circadian clock through three integrated research objectives: (1) mapping the complete protein interactome of core circadian clock proteins (CLOCK, BMAL1, CRY1, PER2, CK1D, and GSK3B) using biochemical and biophysical techniques to reveal complex dynamics and isoform-specific effects; (2) resolving the atomic structures of CRY1 and PER2 proteins and assessing how disease-linked variants affect transcriptional repression of CLOCK-BMAL1; and (3) identifying karyopherin transport factors responsible for nucleocytoplasmic transport of circadian proteins through systematic interaction studies validated by in vitro transport assays and cellular localization studies.

This research directly addresses critical gaps in understanding circadian rhythm disorders, including Delayed Sleep Phase Disorder (DSPD) and Advanced Sleep Phase Disorder (ASPD), as well as associated psychiatric conditions such as depression and anxiety. The work will deliver a comprehensive characterization of the dynamic protein interactions, transcriptional repression mechanisms, and cellular transport processes that sustain the central transcription-translation feedback loop driving circadian oscillations synchronized with the 24-hour day-night cycle.