Project Grant R01EB041643

The National Institutes of Health Office of the Director awarded $672,000 to the University of California, San Diego on August 24, 2026, under the Trans-NIH Research Support program (CFDA 93.310) to develop synthetic uniRFP-based biosensors (SUBs) for real-time detection of small molecules in living systems.

The award funds creation of an experimental platform and predictive machine learning algorithm that engineers the binding pocket of UNAG, a naturally occurring eel fluorescent protein, to recognize diverse small molecules beyond its native ligand bilirubin. The recipient will generate datasets of SUB interactions with new ligands and their corresponding fluorescence outputs, then use those datasets to train ML models that predict biosensor sequences for new ligands directly from chemical structure. The intended outcome is thousands to tens of thousands of functional SUB:ligand pairs linking protein sequence, ligand identity, and optical signal.

The award addresses a gap in biosensing: while current tools such as mass spectrometry and immunoassays are powerful, they are costly, destructive, and confined to specialized facilities, whereas genetically encoded biosensors exist for only a handful of metabolites and ions and lack generalizability. SUBs offer intrinsic fluorescence upon ligand binding without requiring engineered linkages between recognition and reporter domains, enabling continuous, dynamic, in situ measurement of small molecules that serve as biomarkers, signaling molecules, and therapeutic intermediates.

Work is performed at UC San Diego in La Jolla, California, with a period of performance through April 30, 2031. The award is classified as a Project Grant under the Trans-NIH Research Support program.