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Using Conditional Depletion to Probe the Role of Nuclear Hormone Receptors in C. elegans Development

Abstract

Molting is a complex developmental process shared amongst all Ecdysozoans, including insects, crustaceans, and nematodes. Studying molting provides an opportunity to understand the transcriptional regulation of development and identify potential anti-parasitic nematode drug targets. Parasitic nematodes infect over 1 billion individuals worldwide. With rising resistance in parasitic nematodes, the search for anthelmintic drugs continues to be a priority. Molting and its regulatory pathway are novel drug targets. Here I describe my work on nuclear hormone receptors, NHR-23 and NHR-85, and their role in regulating the C. elegans molt. Using the auxin-inducible degradation system I depleted NHR-23 and identified when NHR-23 activity is necessary for the completion of a successful molt. I have found novel phenotypes following timed depletion of NHR-23 in the soma and propose that the transcription factor is a regulator in a large-scale gene oscillatory network coordinating rhythmic skin regeneration. In addition, I have tagged both endogenous proteins and imaged their expression during the molts.

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