Our laboratory investigates how the insulin/IGF-1 pathway regulates development,
aging and metabolism in the nematode Caenorhabditis elegans. In order to identify
new genes that activate or mediate insulin signaling in the context of an intact
organism, we performed novel functional genomic (RNAi) and classic genetic
screens. The RNAi screens identified 467 candidate genes that may participate in insulin-mediated
regulation of development, aging and metabolism. We will determine the roles of these candidate genes as
well as their regulatory relationship with the insulin pathway. We will be particularly interested in novel
signaling or cellular events that modulate or mediate insulin signaling. From the genetic screen, we have
isolated mutants for at least 6 new genes that are likely to function in the steroid signaling pathway,
which is thought to provide a secondary hormonal signal that acts downstream of the insulin pathway to
regulate development and aging. Identification and characterization of these genetic mutants will help to
understand steroid signaling and how it intersects with the insulin pathway.
These studies will uncover the underlying mechanisms of insulin signaling that are potentially conserved in
mammals. As the etiology of diabetes and obesity in humans is thought to involve many yet-to-be
-identified genetic determinants that are associated with defective insulin signaling, our work will provide
insights into these complex disorders. Moreover, our studies will also help to understand organismal aging
as well as serve as an invaluable foundation for studies of human aging-related diseases.
