Date of Award

7-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical and Chemical Engineering and Sciences

First Advisor

Eric A. Guisbert

Second Advisor

Alan C. Leonard

Third Advisor

David J. Carroll

Fourth Advisor

Christopher A. Bashur

Abstract

During stress, a protective cellular network known as the heat shock response (HSR) is induced to maintain protein-folding homeostasis, or proteostasis. While the HSR is essential for stress resistance, its misregulation is associated with neurodegenerative disease and cancer. Using the nematode model organism Caenorhabditis elegans, we have identified the chromatin remodeling complex NuRD (nucleosome remodeling and deacetylase) as a novel regulator of the HSR. Here, we begin with a brief introduction of the HSR and chromatin remodeling complexes in C. elegans, prior to presenting our findings in a series of two chapters. In chapter one, we outline a set of standardized protocols for facilitating accurate measurement of the HSR in C. elegans. In chapter two, we show that dcp-66 and let-418 subunits of the NuRD complex regulate the HSR in divergent ways. This paradigm extends to other stress responses and even to other pathways. Together, this work highlights the power of using C. elegans as a biological tool to discover novel genetic interactions important in physiology and disease.

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