2014 New Investigator Grant
Matt Youngman, Ph.D. Assistant Professor, Department of Biology, Villanova University
Analysis of the role of SMK-1 in the age-dependent regulation of the FOXO transcription factory DAF-16 in Caenorhabditis elegans
Instead of resulting from wear-and-tear, the age-related changes in immunity may represent an orchestrated reshaping of host defense where some aspects are de-emphasized while others are preserved or bolstered. My studies of evolutionarily conserved innate immunity signaling pathways in the roundworm Caenorhabditis elegans suggest that this is true. I have found that while the activity of PMK-1 p38 MAP kinase declines during aging in worms, the activity of the FOXO transcription factor DAF-16 increases in an age-dependent manner and is required for normal resistance to infection in adults. I propose to examine the role of SMK-1, a known genetic interactor of DAF-16, in regulating the activity of DAF-16 during aging. I will test the hypothesis that SMK-1 physically interacts with DAF-16 and influences its target site selection in adult animals. Since FOXO3A, the mammalian orthologue of DAF-16, is essential for the survival of innate immune cells during inflammation and because polymorphisms in FOXO3A are associated with increased longevity in centenarians, I anticipate that my studies will have implications regarding human immunity and aging.