Food consumption and health are intrinsically intertwined. One major determinant in the decision process of food consumption is the ability of virtually all animals to evaluate foods through their gustatory system. Our work over the last 20 years has focused on the role of Gustatory Receptors (GRs) in the model system Drosophila melanogaster. My group, and those of John Carlson and Richard Axel, identified the Drosophila Gr genes, and shortly thereafter, we discovered that two members of this family encode pheromone receptors that control courtship behavior. We initiated a major project to elucidate how Drosophila use their sugar receptors for sweet taste. In contrast to mammals, which have only two sugar receptor genes encoding subunits of a single, broadly tuned, heterodimeric sugar receptor, the genomes of Drosophila and most other insect species contain up to 10 sugar Gr genes. We undertook an extensive molecular genetic analysis to assign specific functions for each of these Gr genes by generating GAL4 and LexA gene knock-in alleles, as well as a sugar-blind Drosophila strain lacking all eight Drosophila melanogaster sugar Gr genes. These studies led to a new model for how insects taste sweet chemicals. We have expanded our interest into other appetitive taste modalities, those of fatty acid taste, acid/sour taste and amino acid taste, and we have discovered that these taste modalities are mediated by a second group of taste receptors, encoded by genes related to ionontropic glutamate receptors (IRs). More recently, we have discovered that Drosophila larvae require ribonucleosides as essential nutrients, and we showed that they use specific members of a small Gr subfamily for this novel taste modality.
A second interest of my laboratory is concerned with the mechanisms that enable animals to monitor and respond to the availability of nutrients internally. A major driver of food consumption, in addition to taste perception, is the internal motivational state (hunger versus satiety), and we are interested in identifying and characterizing the neural origin of sensors that evaluate nutritional content. To this end, we have characterized a brain-based fructose receptor, Gr43a, and we showed that this receptor monitors hemolymph fructose to regulate the feeding activity of flies. Lastly, we have identified a set of neuropeptide releasing neurons in the fly brain, neurons that are competent to produce glucose through the gluconeogenesis pathway. Until now, this process was thought to occur only in the liver and kidney. We have established that the fly brain uses this process for the purpose of neural signaling.