Abstract: Sleep plays a vital role in mammalian physiology. Adequate sleep promotes a healthy immune response, which helps the body fight infections. In the hospital setting, patient sleep is often interrupted due to nighttime nursing care, noise, and artificial light. Sepsis is the leading cause of death in US hospitals. This condition develops when an infection induces a dysregulated immune response, culminating in organ dysfunction. Despite modern medical treatments, the mortality rate for severe sepsis remains very high (30-50%). Prior reports suggest that sleep interruption exacerbates sepsis in mice, increasing animal mortality. However, the mechanisms behind these effects have not been elucidated. This proposal will confirm that sleep interruption exacerbates sepsis in mice, and determine the mechanism of this effect. The knowledge gained will create a foundation for future studies that investigate the intersection between sepsis and sleep in humans. Ultimately, septic patients may benefit from interventions to improve their sleep quantity and quality, or pharmacological interventions to reverse the effects of poor sleep. Additionally, this proposal will provide training opportunities for students enrolled in the Medical School, Masters in Biomedical Science and upcoming PhD in Biomedical Science programs at Mercer University. The graduate student population of Mercer is 64.5% female, 24.5% Black, and 5% Hispanic. The student population also contains a high proportion of people from rural, underserved areas and a significant number of first-generation college graduates. By participating in this project, our students will gain critical research experience, acquiring skills for in vivo and in vitro research techniques, data analysis and statistical analysis, and will gain the opportunity to present their research at a national conference. These activities will greatly enhance their career opportunities and strengthen the infrastructure of research at Mercer University.