Thursday, November 21, 2024
11/21/2024
PROJECT SUMMARY Recent data has shown that individual taste modalities may not be completely segregated with specific cell types in the taste bud which has begun to question the strict roles previously attributed to the various subsets of cells within the mammalian taste bud. Using fatty acid taste as a model, where both Type II and Type III cells have been implicated in in fatty acid signaling, we will attempt to generate the data necessary in this exploratory research program to be able to tackle larger questions surrounding the cell type function within the taste bud. To accomplish this, however, requires we have a thorough understanding of the cellular and molecular underpinnings of fatty acid transduction in Type II and III cells. Moreover, given the emerging data that shows pronounced sex differences in fatty acid taste signaling and its regulation, this project includes a careful analysis of signaling in males and females (at various stages) using a cell-based approach. Specifically, we will test the hypothesis that Type II and Type III cells both respond to fatty acids but do so via different transduction pathways that may ultimately reflect a different role in these cell types. Our goal is to elucidate the transduction pathways for two classes of fatty acids in the mammalian taste system in Type II and Type III cells and identify any potential sex differences in these pathways. The two-year R21 mechanisms is ideally suited to accomplish these important goals in a timely fashion. Once armed with these data on the mechanics of signaling for long chain unsaturated fatty acids (lcUFAs) and medium chain saturated fatty acids (mcSFAs) in Type II and III from males and females, it will be possible to directly assess the role of these cell types in signal processing within the taste bud. For example, our working view on the function of these cell types is that Type II cells are involved most directly in the initial signal transduction for fatty acids while Type III cells perform a more modulatory role in response to changes associated with dietary experience and/or disease (obesity; diabetes). To test this will require identification of important targets within these pathways so that experiments like cell type specific manipulation of gene expression can tease apart the functional differences. To generate the necessary information, we will use patch clamp recording and functional calcium imaging in association with pharmacological interventions and ion substitution to elucidate the transduction pathway for these two classes of fatty acids in genetically identified Type II and Type III cells. To address the sex specificity within these pathways, we will compare males, females in proestrus, females in estrus, and ovariectomized (OVX) females with and without hormone replacement to address two specific aims: • To elucidate long chain unsaturated fatty acid transduction in Type II and Type III cells (Aim 1) • To explore the signaling elements in GPR84 transduction pathway in taste cells (Aim 2) This will provide the necessary background data to allow more detailed exploration of the role of fat taste in the peripheral gustatory system and its regulation by the endocrine system due to effects of diet and disease.
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