Submission Date

8-3-2026

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.

Project Description

Protein folding is essential for maintaining cellular function, and disruptions in this process can lead to protein misfolding, aggregation, and loss of protein homeostasis. In Saccharomyces cerevisiae, the Ribosome-Associated Complex (RAC) and the Nascent Polypeptide-Associated Complex (NAC) are ribosome-associated chaperone systems that assist nascent polypeptides during translation and help with protein folding. Although RAC has been shown to suppress protein misfolding and prion formation, the role of NAC and its relationship with RAC is still being investigated. This study examines RAC and NAC’s effect on protein aggregation by quantifying insoluble protein accumulation in yeast strains containing deletions or human ortholog replacements of these chaperone complexes. Insoluble protein fractions were isolated from ten yeast cultures representing nine unique genetic backgrounds, and protein concentration was quantified using a bicinchoninic acid (BCA) protein assay. Analysis of all trials identified significantly greater insoluble protein accumulation in the strain lacking RAC while expressing human NAC compared with the yeast RAC/yeast NAC control. Because the heat shock response appeared reduced in cultures above OD600 0.6, a secondary analysis was conducted using only cultures between OD600 0.4 and 0.6. In this restricted analysis, strains lacking RAC continued to show higher model-estimated means, but no differences were statistically significant. The heat shock control also showed greater insoluble protein accumulation after restricting the analysis to the target growth range. These findings suggest that both chaperone composition and culture density may influence the amount of aggregation within yeast. Continued investigation of these conserved ribosome-associated chaperones may improve our understanding of the mechanisms that maintain protein homeostasis in eukaryotic cells.

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Available to Ursinus community only.

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