Project Summary Sleep and pregnancy appear to have a bidirectional relationship: pregnancy alters sleep by imposing strong sleep drive (somnolence) during the first trimester, and in turn inadequate sleep is associated with health complications in the mother and her offspring. Despite these correlations there is little mechanistic understanding of the relationship between sleep and pregnancy. Based on a simple but striking observation I made in Drosophila melanogaster, I have developed a model that allows for study of the causes and consequences of reproductive sleep need. I found that sleep is strongly upregulated during the one to two weeks females experience gravidity (the state of carrying young). I call this phenomenon mating-induced somnolence, and this proposal takes steps to uncover its function and underlying mechanisms with the goal of addressing the severely understudied yet critical interplay between sleep, pregnancy, and women’s health. My first Aim will assess the function of increased sleep in female Drosophila after mating. I hypothesize that sleep is promoted to compensate for the physiological burden of reproduction. I will test this idea by characterizing various measures of health of the mother and her offspring – including reproductive health, developmental viability of progeny, and gut health – while preventing the mating-dependent increase in sleep. My second Aim will determine the mating-status signals that promote sleep. There are several pathways that orchestrate the post-copulatory behavioral and physiological state, and I will perform manipulations in each of these pathways to determine their necessity or sufficiency in generating mating-induced somnolence. My third Aim is an exploratory aim that characterizes the ways known sleep circuitry in Drosophila contributes to, and is altered by, mating-induced somnolence. I will achieve this through a perturbation-based screen to identify which sleep neurons are required for the post-mating somnolent state, and via characterization of physiological changes to a key sleep circuit during mating-induced somnolence. This proposal will help elucidate the mechanisms and consequences of gravidity-dependent sleep regulation, something of great public health significance given the disproportionate prevalence of insomnia in women and the susceptibility of women and their children to negative health consequences during pregnancy. Further, Drosophila mating-induced somnolence provides an opportunity to study the way sleep need is measured, regulated, and fulfilled in general, which is my long term goal as an independent academic researcher. The hands-on mentorship from my sponsor Dr. Dragana Rogulja and co-sponsor Dr. Michael Rosbash will ensure my successful completion of this research proposal. As I push to expand my technical skills, knowledge base, scientific communication, and mentoring proficiency throughout my training, they will provide critical professional guidance towards achi...