A role for adenylyl cyclase in innate immune signaling

Olivia Ruth 

Advisor:  Dr. Jennifer PowellOlivia Ruth

All classes of life must be able to protect themselves against infection. The innate immune system, which is capable of recognizing a wide variety of microorganisms and acting immediately to eliminate them, provides a primary line of defense for all plants and animals. One animal that has become increasingly popular for studies of the innate immune system is the nematode Caenorhabditis elegans. In many organisms, the innate immune system functions through cell receptors called pattern-recognition receptors (PRRs). PRRs alert the host to the presence of infection by recognizing pathogen associated molecular patterns (PAMPs). A screen of putative PRRs in C. elegans identified a G protein-coupled receptor called FSHR-1, which is required to illicit an immune response to diverse pathogens. FSHR-1 is known to act in the intestine, but its signaling pathway remains unknown. Previous work has shown that the G-alpha-s subunit GSA-1 is required for intestinal immunity, and we suspect it may be critical for the activation of FSHR-1. C. elegans has four known genes encoding adenylyl cyclase, a downstream signaling element in GPCR-mediated signaling that catalyzes the formation of the critical second messenger, cyclic AMP. Three of these four genes have been tested for a role in innate immunity, all showing no immune phenotype. We propose to investigate whether the remaining adenylyl cyclase gene, acy-4, has a role in defense against intestinal infection, acting downstream of FSHR-1, through a series of RNA interference assays.