Project Grant R00GM154060

The National Institute of General Medical Sciences awarded the University of Wisconsin – Madison $249,000 on July 15, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to investigate TULP3 protein function in primary cilia signaling and ciliogenesis.

The research addresses defects in primary cilia—cellular signaling hubs that sense extracellular signals including odorants, metabolites, light, and neurotransmitters—which are linked to developmental disorders, immune dysfunction, diabetes, obesity, Parkinson's disease, and cancer. The project will develop tools to dissect primary cilia function, including synchronized ciliogenesis protocols in human retinal pigmented epithelial cells coupled with microscopy and phosphoproteomic mass spectrometry to map signaling events temporally and spatially. The work focuses on TULP3, a 50 kDa ciliary protein, testing hypotheses that TULP3 regulates G-protein-coupled receptor traffic prior to ciliary entry and licenses axoneme formation. Patient mutations identified from genome-wide association databases will probe links between protein function and human disease. Constitutive expression of TULP3 mutants in knockout backgrounds will generate tools to perturb select functions and probe function-specific binding domains and partners.

Work is performed at Palo Alto, California, with performance period through June 30, 2029. This is a Project Grant assistance award.