Senior Honors Projects, 2010-current

Preferred Name - First Author

Gormley, Claire

Date of Award

Spring 2017

Document Type

Thesis

Degree Name

Bachelor of Science (BS)

Department

Department of Biology

Advisor(s)

Dr. Tim Bloss

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.

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