Senior Project Advisor

Lina Dahlberg

Document Type

Project

Publication Date

Spring 2024

Keywords

ERAD, C. elegans, cellular stress

Abstract

Protein misfolding is associated with many different diseases such as Alzheimer’s disease, Parkinson’s disease, and cystic fibrosis. Cells prevent the accumulation of misfolded proteins through conserved pathways, including Endoplasmic Reticulum Associated Degradation (ERAD). In the absence of proper ERAD function, cellular homeostasis is disrupted, and cells can become stressed. The ERAD mechanism is not fully understood, but it is becoming clear that the intersection of gene regulation and protein degradation are tightly linked (1). We approached this intersection using a strain of C. elegans that is lacking the gene F26F4.9, which encodes a putative ortholog of the mammalian ERAD gene SelenoS/VIMP. Preliminary data from our lab shows loss of VIMP does not induce a significant ER stress response in C. elegans, as measured by the transgenic reporter, Phsp-4::GFP. We also saw that in animals lacking VIMP, when stress is induced genetically or by the glycosylation-blocking drug tunicamycin, upregulation of the hsp-4 (BiP) gene is reduced. These data suggest that VIMP is required to elicit the ER stress response. We repeated these experiments and found conflicting data suggesting that VIMP increases the ER stress response. The Phsp-4 reporter system is convenient for observing changes in a single, well-characterized UPR gene, but questions remain about global gene expression. To determine what other genetic pathways might be regulated by F26F4.9, we undertook a transcriptomic approach to determine how global gene expression changes when C. elegans is missing that gene. Within this data set, we identified four strains of interest that we are working on to identify pathways and networks that are differentially regulated in the presence and absence of F26F4.9.

Department

Biology

Type

Text

Rights

Copying of this document in whole or in part is allowable only for scholarly purposes. It is understood, however, that any copying or publication of this document for commercial purposes, or for financial gain, shall not be allowed without the author’s written permission.

Language

English

Format

application/pdf

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