Submission Date

4-28-2025

Document Type

Paper- Restricted to Campus Access

Department

Biology

Adviser

Dale Cameron

Committee Member

Dale Cameron

Committee Member

Rebecca Lyczak

Department Chair

Denise Finney

External Reviewer

Colin Conine

Distinguished Honors

This paper has met the requirements for Distinguished Honors.

Project Description

The process of protein synthesis is easily influenced by fluctuations in an organism’s internal and external environments. When proteostasis is disrupted, proteins may achieve unintended 3-dimensional conformations, presenting an avenue for inappropriate interactions and aggregation. Protein aggregation is commonly associated with various mammalian neurodegenerative diseases, including Creutzfeldt-Jakob, Parkinson’s, and Huntington’s diseases. Prions and prion-like proteins, including PrPsc, ⍺-synuclein, and huntingtin — respectively associated with the aforementioned diseases — are unique in their ability to transmit their misfolded conformation onto other correctly folded proteins. To prevent this transmission and the subsequent consequences, organisms have evolved quality control systems to oversee proteostasis. Among these mechanisms are molecular chaperones, a group of proteins that survey and facilitate protein folding and/or localization. Some chaperones are known to associate with the protein synthesis machinery to guide the folding and localization of nascent polypeptides prior to the termination of their synthesis. Two chaperone complexes, the Ribosome-Associated Complex (RAC) and Nascent Polypeptide-Associated Complex (NAC) are conserved across eukaryotes. Our lab has previously shown that the human RAC can rescue deficiencies associated with loss of endogenous RAC in Saccharomyces cerevisiae, but the capabilities of the human NAC to replace the yeast NAC have gone largely uncharacterized. Thus, we have generated a comprehensive set of yeast strains to characterize the functions of the human NAC subunits alone and in concert with one another, specifically in the contexts of endoplasmic reticulum stress response and prion formation.

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