Senior Honors Projects, 2010-2019

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Date of Graduation

Fall 2019

Document Type

Thesis

Degree Name

Bachelor of Science (BS)

Department

Department of Biology

Advisor(s)

Tim Bloss

Abstract

Cells experiencing misfolded protein stress can become debilitated and die, consistent with this stress being linked to numerous diseases. When misfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response (UPR) initiates mechanisms that resolve this stress or trigger apoptosis, dependent on the severity and/or duration of the stress. The nascent polypeptide-associated complex (NAC) is a heterodimeric chaperone that mediates proper protein folding and localization during translation; depletion of the NAC promotes misfolded protein stress in the ER, resulting in the initiation of the UPR in affected cells. The relationship between the NAC and the UPR is not well understood, nor is it known if this relationship differs depending on cell type. Our goal is to characterize this relationship in the model organism C. elegans, where cell lineages display variable sensitivities to misfolded protein stress. Via RNA interference, we are depleting the NAC in worm strains expressing cell type-specific fluorescent proteins and characterizing the nature, number and position of these cells throughout the life of the worm. Depletion of the NAC in worms expressing neuron-specific red fluorescent protein decreased the number of observable neurons in the ventral nerve cord while mislocalizing a subset of the neurons that remained. Concordantly, affected worms displayed movement defects consistent with disruption of ventral nerve cord function. The loss and mislocalization of neurons in response to NAC depletion are consistent with previous findings in C. elegans showing neurons more susceptible to damage and death during misfolded protein stress relative to other cell types. Through these experiments, we hope to better understand the role of the NAC during misfolded protein stress response and how depletion of the NAC contributes to the debilitation of the nervous system.

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