Our laboratory is interested in dissecting animal behaviors that are driven by TRP channels and other peripheral sensory receptors. We isolated the founding member of the TRP superfamily of cation channels as part of our characterization of Drosophila visual transduction, and later identified mammalian TRP channels. We now know that the TRP superfamily is comprised of 28 mammalian channels as well as 13 Drosophila proteins, most of which play important roles in sensory physiology. To characterize behaviors that function through TRP channels we are focusing on the fruit fly, with a particular emphasis on behaviors impacted by chemosensory and thermal input. We are also dissecting the roles of other receptors, such as gustatory receptors, in controlling animal behaviors. As part of these projects, we are characterizing the cellular and molecular mechanisms through which sensory input controls plasticity in flies.

In addition to using fly TRP channels and gustatory receptors to provide basic insights into sensory signaling and animal behavior, we are exploiting these channels and receptors as tools to control insect pests that spread disease. Insect TRP channels are expressed in olfactory receptor neurons, and we found that they are targets for many naturally-occurring repellents. We found that fruit flies are exquisitely sensitive to avoiding the most commonly used synthetic repellent, DEET, through gustatory receptors in gustatory receptor neurons. Thus, DEET may be effective in insect control through its dual action in deterring insects simultaneously through contact and non-contact chemosensation, rather than exclusively through the sense of smell.

TRP channels also cause human disease, including the early childhood neurodegenerative disease, mucolipidosis type IV (MLIV). Using flies as an animal model for MLIV, we dissected the cellular mechanism of neurodegeneration and proposed a therapeutic approach for treating this disease. To characterize mechanisms underlying neurodegeneration, we are also exploiting the visual system to dissect the underlying bases for the retinal degenerations that result from mutations that disrupt the TRP channel, rhodopsin and other signaling molecules.