DESCRIPTION (provided by applicant) Appropriate food choices are critical for the acquisition of nutrients for growth, energy expenditure and reproduction. Taste perception is the primary sensory modality for the identification of nutritious compounds, such as carbohydrates, proteins, salts and fats, as well as harmful and toxic compounds, such as alkaloids, terpenoids and phenols, chemicals perceived as bitter by humans. Drosophila has served as an important model system to dissect the molecular basis of many sensory processes, including taste perception. The genomic/genetic resources are excellent and researchers have an impressive array of molecular-genetic, electrophysiological and imaging tools at their disposal, while the system is also amenable to elegant behavioral assays. Even though mammals and insects express evolutionarily distinct sets of taste receptors, the overall organization of taste sensory systems and especially the logic of taste coding are similar. Thus, the fly provides an opportunity to uncover basic mechanisms of taste perception, as well as organizing principle of their neural circuits. The Drosophila genome harbors 68 Gustatory receptor (Gr) genes, a subfamily of eight is thought to encode all putative sugar receptors. However, a model has emerged over the last few years that posits that only two heterodimeric sugar receptors (Gr5a/Gr64a and Gr5a/Gr64f) mediate most or all of sweet taste. We have tested this hypothesis using specific knock-in/expression alleles, as well as `sugar blind' Drosophila strains. These studies let us conclude that two major premises of this model need revision: First, Gr64a is not a major mediator of sweet taste and second, all sugar Gr proteins participate as units of functional sweet taste receptors. Moreover, while sugar receptors do function as multimeric complexes, Gr composition for most taste receptors is unknown. This gap in knowledge will be systematically filled with a methodical rescue strategy. We will also build on our recent discovery that sweet taste cells in the fly are not exclusively tuned to sugars, but also respond t fatty acids, another important nutritional component for almost all animals, including fruit flies.In preliminary studies, we have identified the first receptor gene necessary for fatty acid taste, a member of the Ionotropic receptor gene family. We will investigate the role of other members if this gene family by studying both their expression, as well as their function in fatty acid taste. Lastly, we discovered an entirely new taste modality, tuned to carboxylic acids but not acid in general. Carboxylic acids are generic components present in many fruits. We will determine the response profile of taste cells that specifically respond to these food components, and possibly to amino acids, and search for the receptors that recognize these compounds using a targeted candidate gene approach.