Despite spending approximately one-third of our lives asleep, sleep remains a major mystery of biology, with unelucidated properties about its regulation and function. What is clear is that all animals studied engage in a sleep-like state and that sleep is critical for many biological functions, including control of fitness, metabolism, immune system, and cardiovascular system (1-6). Despite these profound effects, our understanding of the neural and molecular basis of sleep regulation and how sleep is influenced by an animal’s internal and external environment remains incomplete. The traditional methods to study the control of sleep as more of a brain-centric process is not sufficient to fully understand the regulation of sleep. Molecular clocks are found in most body tissues (7) where they regulate local tissue-specific function, transcription, and can also contribute to systemic functions. Additionally, changes in sleep are associated with molecular changes in the periphery (8). Theoretically then, circadian, or homeostatic regulation of sleep could arise from the periphery. It is therefore tempting to speculate that sleep disruption can occur due to effects on the brain, peripheral organ systems, or their communication. From a systematic screen using the D. melanogaster, which has historically led the way in the elucidation of circadian clock and sleep mechanisms (9-10), a multitude of genes secreted from the gut, abdominal fat, or body wall muscle including serine endopeptidases were discovered as potential novel sleep regulators. Emerging evidence has indicated a bidirectional relationship between sleep and gut reactive oxygen species (ROS) levels (11). Thus, this project sought to delve deeper into the role of a specific serine endopeptidase encoded by CG11037 by investigating how the knockdown of this gene can affect ROS levels in various tissues especially the gut as well as sleep and survival.