Federal Project Grant Award Summary

Northwestern University's Sponsored Research Division received a $739,353 Project Grant from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), effective February 1, 2026, through January 31, 2031. The award supports fundamental research investigating the structural and molecular mechanisms of Store-Operated Calcium Release-Activated Calcium (CRAC) channels, which are critical regulators of cellular calcium signaling in immune cells and neuroglial cells. The research employs a multidisciplinary approach integrating photocrosslinking techniques using unnatural amino acids, cryo-electron microscopy structural analysis, and fluorinated phenylalanine analogs to elucidate the binding interface between Orai1 and Stim1 proteins and to characterize the gating mechanisms of Orai1 channels.

The primary deliverables include determination of the molecular and structural basis of Orai1-Stim1 binding interactions and structural characterization of gain-of-function Orai mutants, including variants associated with human disease. This basic science research addresses gaps in understanding CRAC channel regulation, with potential implications for therapeutic development targeting diseases ranging from immunodeficiency to allergic disorders. The research will be conducted at Northwestern University's Chicago, Illinois facility and is structured to advance fundamental knowledge of calcium signaling mechanisms essential to immune cell function and disease pathogenesis.