Proper perception and behavioral response to the environment by humans is essential for our health and well-being. Our understanding of sensory physiology and sensory-driven behavior has greatly benefited from the surprising conservation of mechanisms between humans and model organisms. The study of pheromone-activated courtship behavior in fruit flies in particular, offers an experimentally ideal system that has yielded key insights on the genetic control of behavior. We have recently found that mutations inppk25, a Drosophila gene encoding a sodium channel subunit of the DEG/ENaC family debilitate a male's response to female pheromones. Furthermore, ppk25 function is only required in a few neurons associated with taste hairs on the legs and wings of flies, including several pheromone-sensing hairs, suggesting thatppk25 plays a role in the transduction of pheromone signals. The work supported by this grant will shed new light on Drosophila chemical senses that shares many mechanistic aspects with a wide variety of cell-signaling mechanisms implicated in all aspects of human biology. In addition, as members of the DEG/ENaC superfamily have been implicated in many normal and pathological aspects of human physiology, including hyper- and hypotension, stroke, memory, pain and gustatory perception, the insights we gain on the function of this Drosophila family member will likely add significantly to our understanding of the role this important family of proteins plays in human health. ? ? ?