Senior Honors Projects, 2010-2019
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Date of Graduation
Spring 2017
Document Type
Thesis
Degree Name
Bachelor of Science (BS)
Department
Department of Biology
Advisor(s)
Tim Bloss
Steven G. Cresawn
Jonathan D. Monroe
Abstract
Abstract
Misfolded protein stress has been associated with many types of disease,
including neurodegenerative disorders like Alzheimer’s, Parkinson’s and Huntington’s
disease. When a cell accumulates misfolded proteins in the endoplasmic reticulum,
misfolded protein stress occurs and the unfolded protein response (UPR) is triggered to
induce mechanisms that will allow the cell to either survive or undergo cell death. The
nascent polypeptide associated complex (NAC) is a co-translational chaperone and α/β
heterodimer that manages protein folding and localization, and protects against misfolded
protein stress; changes in NAC function have been linked to both neurodegeneration and
cancer. In these studies, I depleted the βNAC homologue ICD-1 from Caenorhabditis
elegans and characterized changes in cell viability and nature, specifically in neurons,
which are known to be susceptible to misfolded protein stress in the worm. I
hypothesized that the levels of apoptotic cell death would increase in neurons in response
to the misfolded protein stress. RNA interference (RNAi) was used to generate a range of
icd-1 mRNA depletion levels, and the effects were evaluated at the microscopic level in
worm strains expressing neurons marked by fluorescent proteins. Variations in the level
of ICD-1 depletion led to a range of phenotypes, including the hypothesized increased
apoptosis in embryonic neurons, as well as migration defects and changes gene
expression patterns and dendrite and axon growth in adult neurons. These results may
provide significant insights into how the NAC functions in healthy cells and how it
malfunctions during the development of disease.
Recommended Citation
Gormley, Claire, "Characterization of neuronal specific responses to induced misfolded protein stress in Caenorhabditis elegans" (2017). Senior Honors Projects, 2010-2019. 308.
https://commons.lib.jmu.edu/honors201019/308
