# Novel Insights into the Role of Prions in Polyglutamine Protein Homeostasis

> **NIH NIH F31** · DUKE UNIVERSITY · 2024 · $28,337

## Abstract

Abstract
Formation of toxic protein aggregates is a hallmark of neurodegenerative disorders. In some diseases, including
Huntington’s Disease and six subtypes of spinocerebellar ataxia, protein aggregates form due to the expansion
of a CAG repeat in the coding region of a specific gene. This CAG repeat encodes for a polyglutamine tract that
aggregates when expanded, leading to neuronal death. One potential way to treat these diseases is to suppress
polyglutamine aggregation and toxicity. Our laboratory has taken a unique approach to addressing this issue.
Instead of studying polyglutamine in organisms where it aggregates and causes toxicity, we have identified the
social amoeba Dictyostelium discoideum as a proteostatic outlier that is naturally resistant to polyglutamine
aggregation. To investigate this phenomenon, I conducted a proximity labeling screen to identify proteins in
Dictyostelium with increased proximity to polyglutamine-expanded huntingtin, the causative protein in
Huntington’s Disease. Strikingly, I found that many proteins with increased proximity were highly glutamine-rich
and predicted to form prion. This is interesting because prions influence polyglutamine aggregation in a poorly
defined manner. Here I propose to help clarify the role of prion-like proteins in Dictyostelium and their potential
role in suppressing polyglutamine aggregation. Using parallel investigation in Dictyostelium, human cells, and in
vitro experiments, I hope to elucidate the role of prion-like proteins in regulating polyglutamine aggregation.
Additionally, I propose to define the roles of prions in Dictyostelium biology. Together these aims begin and
define the roles of prion-like proteins in Dictyostelium and determine how they influence the solubility of
Dictyostelium’s polyglutamine-rich proteome.

## Key facts

- **NIH application ID:** 10898975
- **Project number:** 1F31GM147941-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Felicia Nicole Williams
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $28,337
- **Award type:** 1
- **Project period:** 2024-05-01 → 2024-11-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898975

## Citation

> US National Institutes of Health, RePORTER application 10898975, Novel Insights into the Role of Prions in Polyglutamine Protein Homeostasis (1F31GM147941-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10898975. Licensed CC0.

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