The regulation of organismal life cycles by genetic components is a research area that has shown great promise in recent years. The process of aging is becoming more important to understand, not only due to the increasing incidence of age-related diseases, but also in order to determine what factors contribute to prolonged health and longevity. A variety of physiological pathways can regulate lifespan in C. elegans nematodes. Among these, one pathway of great interest involves dietary restriction. It is known that “stresses” on the worm, such as reduced food intake, can extend its lifespan. A mutation in the eat-2 gene affects the pharyngeal pumping mechanism whereby the worms ingest bacteria, thus creating a genetic model for dietary restriction. This research investigates the role of steroid signaling in dietary restriction-induced lifespan extension and improved stress resistance, using eat-2 mutant worms as a background and using a heat shock assay to induce stress at various points during the worms’ life cycle. By studying genetic determinants of longevity in C. elegans, my research will help to uncover more information about what can make nematodes long-lived, thus contributing to our understanding of the genetic basis for longevity regulation. More importantly, the existence of human orthologs for many longevity genes in C. elegans suggests that our findings will be valuable in identifying factors that are crucial for human longevity and health.

Inhibitor of differentiation (Id) is a transcription factor that negatively regulates basic helix-loop-helix (bHLH) transcription factors. Of four Ids identified (Id1-4), Id1 and Id3 have been shown to regulate glial development in the central nervous system. In the retina, there is a special type of glia called the Müller glia. Currently, it is not known whether the Ids are important for Müller glial development. Knockout studies in mice demonstrated that Id1/Id3 double knockout (KO) are embryonic lethal, while either Id1 or Id3 KO mice develop grossly normal. We investigated if Id1/Id3 are necessary for Müller glial development by performing Id1 shRNA knockdown (KD) in Id3 KO retinas. Five Id1 shRNAs were tested for their efficiency in NIH 3T3 cells (mouse fibroblast cell line), and the Western blot results showed over 90% decrease in Id1 expression using three shRNAs. We will electroporate Id3 KO retinal explants with these Id1 shRNAs and determine the effects of Id1/Id3 loss on Muller glial development. We expect to see a reduction in the number of Müller glia if Id1/Id3 play a role in their development.