In recent years, olfactory receptors (ORs) have been shown to play a variety of important roles outside of the nose, acting as chemosensors to aid in muscle migration, sperm chemotaxis, and metabolite sensing. In 2009, we identified several ORs which are expressed in the kidney, including the topic of this proposal: Olfr90. We have recently deorphanized Olfr90, and found that it senses chemicals which have been reported to be present in blood and urine. However, these chemicals are not produced by the host - rather, they are metabolites produced by fungi. Recent studies by both our group and others have shown that there are at least three receptors for bacterial metabolites which play important roles in modulating physiological parameters in the host; however, few studies have examined a role for fungal metabolites in vertebrate physiology. In this proposal, we will follow up on this intriguing finding by working to better understand the role of Olfr90 in the kidney by: (I) Further characterizing the ligands to which Olfr90 responds and their physiological relevance, (II) Localizing Olfr90 within the kidney, and (III) Examining the phenotype of Olfr90 knockout mice both at baseline and after exposure to fungal sources. Our considerable experience in molecular biology, cell biology, and renal physiology, including previous work deorphanizing ORs and studying host-microbe interactions, makes us well-suited to explore this exciting new area. Through our studies of this novel signaling pathway, we hope to expand our understanding of host-microbe interactions and to uncover novel roles for ORs in renal physiology.
We recently found that one of the sensors in your nose that helps to mediate smell is also present in the kidney, where it is 'smelling' metabolites of fungi i your blood and/or urine. In this proposal, we will explore this pathway by working to better understand which chemicals this receptor is detecting, by identifying precisely where in the kidney this receptor is found, and by studying the role of this receptor in kidney function.
