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Russell Day


Summer Research Description: G-protein coupled receptors (GPCR) transmit a large number of signaling pathways that are common targets for the treatment of a wide range of diseases. Once stimulated by a ligand on the outer surface of the cell, GPCRs trigger various intracellular signaling cascade to affect a specific cellar process. An in vivo phenotypic zebrafish development chemical screen identified an inhibitor of ovarian cancer G-protein-coupled receptor 1 (OGR1). Recent studies have shown that OGR1 responds specifically to extracellular protons. Although OGR1 has been shown to play a critical role in various models of inflammation, a developmental role for the receptor has not yet been described.  Therefore, this study investigates the expression and function of OGR1 in early development of zebrafish. The expression pattern of OGR1 during zebrafish embryogenesis was quantified by real time polymerase chain reaction (qPCR), showing the RNA is not maternally deposited but is dynamically expressed throughout development. Furthermore, anti-sense morpholino oligonucleotides were injected to determine loss of function phenotypes. Resulting phenotypes were less severe than chemical treatments, suggesting that the compound acts through additional mechanisms, potentially other members of the proton sensing GPCR family.