Genetic analysis of innate immunity in Caenorhabditis elegans

Abstract

Pathogen resistance in Caenorhabditis elegans is a model for studying innate immunity. Several conserved activators in the p38 PMK-1 pathway have been identified and are required for pathogen resistance to the bacterium Pseudomonas aeroginosa. Thus far, screens have been performed to identify mutants that are susceptible to pathogen infection. Here, I will discuss a mek-1 suppressor screen that was performed to look for more components of the p38 PMK-1 pathway. Aided by the agls219 reporter, mutants with high levels of GFP expression were isolated and screened for suppression of the Esp phenotype of mek-1. Several independently isolated strong suppressor mutants were isolated and separated into possible complementation groups using pooled lysate SNP mapping. Interested to see if the mutants would also affect other stress response pathways in the worm, I tested the mutants for heavy metal sensitivity. Five out of the six strong Esp suppressor mutants did not suppress the heavy metal sensitivity of mek-1, suggesting that our mutants are more specifically affecting the pathogen resistance pathway and not the heavy metal stress response pathway. Future work will involve measuring PMK-1 phosphorylation levels using Western blots and fine mapping the mutants.