Exploring the mechanisms of stress responses in Caenorhabditis elegans

Sleep is essential for maintaining normal physiological functions. However, sleep prevents behaviors such as foraging, reproduction, and avoidance of impending threats, that are also essential for survival. Thus, animals must tightly control transitions between sleep and arousal. How these transitions are regulated is not clear. In this project, the model organism Caenorhabditis elegans, a small nematode, will be leveraged to understand how threat detection and avoidance, and the sleep needed to recover from these threats are regulated at the cellular and molecular level. To do this, the stress response of C. elegans will be closely examined at the cellular and genetic level, using tools that allow for precise manipulation of the circuitry underlying stress induced behaviors. As the neurochemistry of the C. elegans nervous system, and the genetics of sleep are conserved, this project will provide insight into stress responses in more complex animals, like mammals. This research will be conducted primarily by undergraduates and master-level students, which will help prepare them for careers in science and medicine. These students will also participate in science outreach, in partnership with the Samuel Gompers School, a K-8 public school. Through this outreach, students will share the process and results of this project with grade school children in the community surrounding Saint Joseph’s. Structured, long-term mentoring networks will be established between SJU undergraduates and students from the Samuel Gompers School to help promote the success of both populations as they move forward in their careers. To gain new insight into the stress response of animals, this project aims to characterize new mechanisms controlling avoidance and recovery sleep. To do this, a relatively simple, 13-celled neural circuit in C. elegans, that underlies these behaviors, will be interrogated. Using a bipartite expression system, each of the 13 cells will be individually inhibited using histamine-gated chloride channels, or activated using channel rhodopsin. During these manipulations, threat avoidance, sleep, and arousal will be measured. Next, a collection of signaling molecules identified by the Nelson lab and known to regulate stress behaviors, will be expressed in each cell individually to determine the precise sites of action. To identify novel pathways, mutants for all G-protein coupled receptors expressed in these cells will be analyzed during the stress response. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.