Submission Date

7-23-2026

Document Type

Paper- Restricted to Campus Access

Department

Biology

Faculty Mentor

Dale Cameron

Comments

Presented during the 28th Annual Summer Fellows Symposium, July 24, 2026 at Ursinus College.

This research was funded by an NIH Grant (Award Number R15GM119081).

Project Description

Correct protein folding in the endoplasmic reticulum (ER) is essential for normal cellular function, and when proteins are misfolded in the ER this causes the cell to mount a stress response. Specifically, the unfolded protein response (UPR) is a highly conserved signaling pathway that aims to restore ER proteostasis. To help ensure proteins fold properly, ribosome-associated chaperone complexes associate with nascent chains; these complexes include the Ribosome Associated Complex (RAC) and the Nascent-polypeptide Associated Complex (NAC). RAC and NAC are evolutionarily conserved in both humans and Saccharomyces cerevisiae, but it’s unclear if the human orthologs can function within S. cerevisiae under ER stress. The goal of this project is to determine how the RAC and NAC contribute to ER stress tolerance in S. cerevisiae. To do this, I utilized several strains of yeast that contain pairwise combinations of gene deletions or human ortholog replacements of RAC and NAC, and induced ER stress by utilizing tunicamycin (TM), which activates the UPR. I then quantified the degree to which the UPR is activated by western blotting for Kar2, a chaperone encoded by a common UPR target gene. Using ImageJ densitometry and normalized to a loading control, I was able to compare UPR activation between the several strains. I found that the native S. cerevisiae homologue of RAC resulted in a weaker UPR and changes in NAC had negligible effects. These findings may help us better understand chaperone dysfunction in human diseases that feature ER stress and protein misfolding, such as in Alzheimer’s.

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