Mechanistic studies of sickness sleep

Project Summary In the nematode C. elegans as in other animals, sickness is associated with reduced movement, reduced feeding, and increased sleep. Sickness behavior in worms is induced by environmental stressors including heat shock, ultraviolet light, and infection. This behavioral program during sickness is regulated by worm central neurons that are activated by the cytokine epidermal growth factor (EGF). EGF causes reduced activity in worms, flies, fish, and mice, but the mechanisms of EGF activation itself during sickness are not clear. We will use C. elegans to study the mechanism of EGF regulation during sickness. In Aim 1, we will determine where (from which cells) and when EGF is released to promote sickness behavior. To identify other regulators of EGF activation, in Aim 2, we will perform genome-wide discovery screens for genes required for sickness behavior. In Aim 3, we will test the hypothesis that sickness behavior supports survival during sickness. A long- term goal of these studies is to identify candidate signaling molecules for developing diagnostics and treatments of sleepiness during sickness and to understand the importance of sleep in promoting recovery from illness.