Our principal goals are to identify the neuronal and molecular components of the sleep homeostat, to understand how those components cooperate to sense and control sleep-wake state, and to reveal how molecular and neural homeostatic pathways impact brain function, health, and disease. Our strategy employs genetic tools primarily in the fruit fly Drosophila to dissect, manipulate and monitor the homeostatic machinery. This approach builds on our research to understand the molecular basis of circadian (~24 h) behavior which have revealed sleep mechanisms conserved between invertebrates and vertebrates and incorporates work in both mice and humans.