The dual role of FSHR-1 in oxidative stress and innate immunity in Caenorhabditis elegans

Elizabeth MillerElizabeth Miller

Advisor:  Dr. Jennifer Powell

Most organisms are exposed to an incalculable amount of bacteria in the course of their natural lifecycle. These bacteria can often be pathogenic and it is essential that organisms are able to detect and quickly respond defensively to infection. The primary response to infection is directed by the innate immune system, which identifies and kills invading microbial pathogens. The invertebrate Caenorhabditis elegans is particularly suited as a model for research on immune responses because it lacks a complex adaptive immune response, has relatively short generation times, and it is susceptible to intestinal infection through the use of pathogenic bacteria such as Pseudomonas aeruginosa, a bacterium which has been shown to kill C.elegans though an infection-like process. In C.elegans, fshr-1 is required for the induction of a range of antimicrobial compounds induced by P.aeruginosa. Previous data suggest reactive oxygen species (ROS) may also be critical in the response to infection by microbial pathogens, and could be involved in the fshr-1 response to P.aeruginosa. The same underlying mechanisms that make ROS an effective defense response against bacterial pathogens, however, also make ROS dangerous for normal cellular functions. Thus, when ROS are generated as part of an immune response, detoxification enzymes must also be produced as part of an oxidative stress response, so that the organism itself is not damaged. We are looking at FSHR-1’s role in the production and detoxification of ROS, thus providing a molecular connection between oxidative stress and the innate immune response conserved among multicellular organisms.