Weiqing Li

weiqing@u.washington.edu
Assistant Professor, Department of Biological Structure

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Our laboratory investigates the neuroendocrine control of insulin and steroid signaling in development, aging and metabolism in the nematode Caenorhabditis elegans.  In response to harsh environmental conditions, worms delay reproductive growth by entering a dormant larval stage, called dauer arrest, during which development pauses, a long-life program is turned on and metabolism is shifted towards fat accumulation.  Previous studies showed that the insulin signals generated in the sensory neurons (brain of the worm) and steroid hormones produced by another type of head neuron are required in inhibiting dauer arrest.  We aim to genetically dissect these hormonal events and investigate how the neuroendocrine tissues regulate diverse biological processes in the context of an intact animal.  In order to identify new genes that activate or mediate insulin and steroid signaling at the organismal level, we performed novel functional genomic (RNAi) and classical genetic screens, using dauer arrest as a readout. 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.  For genetic screens, we utilized a worm mutant with a defective cholesterol transporter (mutations in its human homolog result in[LINK] Niemann-Pick type C neurodegeration) to identify new components of the steroid signaling pathway.  We have isolated mutants for at least 6 new genes, some of which may function in neurons, as movement is impaired in these mutants.  Identification and characterization of these genetic mutants will help to understand the novel neuronally-controlled steroid signaling event.  Our studies will uncover underlying mechanisms of insulin and steroid signaling that are potentially conserved in humans.  Identification of genetic determinants involved in insulin and steroid signaling will provide insights into complex disorders such as diabetes and aging-related diseases.