Check out the link below for Wendy Hanna-Rose’s story on identifying nicotinamide as the first endogenous activator of sensory TRPV channels in invertebrates. The most notable role for our TRPV channels are as heat sensors, and compounds such as capsaicin in chili peppers can activate them. Invertebrates seem to use TRPV channels mainly for mechanosensation – they have been studied for years in C. elegans, but nobody had ever been able to functionally express them until Wendy’s lab did a series of elegant genetic studies that suggested nicotinamide could be an agonist for worm TRPVs. Her grad student Avni Upadhyay found that in worm mutants with elevated nicotinamide levels, cells expressing two TRPV channel subunits OSM-9 and OCR-4 die. This phenotype could be rescued by knocking out either TRPV subunit. We confirmed that nicotinamide directly activates both worm and fly TRPVs. We also worked with Will Hancock’s lab (and Keith Mickoajczyk in particular) to figure out that nicotinamide-sensitive worm TRPVs form functional channels as a 2:2 heteromer of OSM-9 and OCR-4 subunits.
Jegla Lab
