Daily wake-sleep cycles are a pervasive feature of animal life, and disruptions in sleep are associated with numerous health related disorders in humans. Drosophila has proven to be an excellent genetic model system to study sleep. Several different genetic screens in Drosophila have been performed that have led to the identification of genes that regulate sleep. Although the majority of sleep in Drosophila occurs during the night, similar to many diurnal animals, they exhibit a mid-day siesta which is strongly regulated by ambient temperature. For example, during hot days, both flies and humans show an increase in daytime sleepiness (?siesta?) and a decrease in nocturnal sleep quality. Increased siesta during warm days is an important seasonal adaptation that animals exhibit to minimize the deleterious effects of exposure to heat and possibly UV irradiation. Despite the advantage of a quiescent period to avoid excessive daytime heat, this comes at the potential cost of another core survival behavior, feeding. The balance between sleeping and eating is central to human well-being. Many of the genetic screens in Drosophila and other model organisms have been focused on nighttime sleep. In this exploratory/developmental research proposal novel genetic screens will be used to identify the genetic complexity underlying daytime sleepiness/wakefulness. Excessive daytime sleepiness (?sickness? behavior) is associated with many diseases in humans, such as narcolepsy, diabetes type 2, and Parkinson?s. In many of these cases, the increased daytime sleep has been ascribed to higher then usual skin temperature during the day, further highlighting the critical role of the thermal environment on sleep and the sleep-inducing effects of heat during the day. Thus, daytime sleepiness is tightly linked to thermal environment, metabolism and its mis-regulation contributes to a variety of disease states. It is anticipated that the novel genetic screens employed herein will provide novel genes and pathways that provide fundamental new insights underlying the regulation of daytime wakefulness and sleepiness, and how these cognitive states are modulated by environmental factors and physiologic state.
This proposal will use novel genetic screens in the model animal organism Drosophila to identify genes that regulate daytime sleepiness and wakefulness. Numerous diseases, such as diabetes, are associated with increased daytime sleep (?sickness? behavior). Thus, a better understanding of genes that regulate wake-sleep states should provide new insights into sleep regulation and how its mis-regulation contributes to diseases.
