The innate immune system acts as an organism’s first line of defense against invading pathogens. It accomplishes this by using pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) to recognize and destroy invaders. While the mechanisms for innate immunity in response to pathogens have been studied, the genetic and environmental influences that govern innate immune development are unknown. In the Ackley lab we use Caenorhabditis elegans, a soil-dwelling bacterivore nematode, to study the genetics of innate immunity. My project focuses on how mutations in the mab-5 gene affect resistance to bacterial pathogens. mab-5 is a Hox-family transcription factor that has primarily been studied in early organismal development, but transcriptome analyses of both gain and loss-of-function mutations identified mab-5 regulation of innate immune genes. I have tested the resistance of four mab-5 mutant strains following exposure to a bacterial pathogen, Staphylococcus epidermidis, and compared survival to animals fed a normal diet of non-pathogenic Escherichia coli. I have tested the wild-type strain, N2, two loss-of-function mutations, mab-5(gk670) and mab-5(e1239), and one gain-of- function mutant, mab-5(e1750). I have found that the mab-5(e1750) strain has increased resistance compared to the loss-of-function and wild-type strains during the first week following exposure to S. epidermidis. This is consistent with our observation that increased mab-5 activity leads to increased expression of innate immune genes. To corroborate this observation I am testing another potential gain-of-function line, wgIs77, from the ModEncode project, which has an integrated MAB-5::GFP fusion protein. I am also using a transcriptional mab-5 gfp reporter, muIs16, to monitor when and where mab-5 expression might be occurring in animals after bacterial infection. Together, the results of this project will help illuminate the mechanisms of innate immune pathway activation and the role that transcriptional regulation plays in organismal health.
