# Investigation into protein quality control pathways in Dictyostelium discoideum

> **NIH NIH R35** · DUKE UNIVERSITY · 2022 · $402,500

## Abstract

Abstract
Protein aggregation is a hallmark of at least 71 diseases. Protein aggregates are caused by an imbalance in
protein homeostasis resulting in the accumulation of misfolded proteins. One major question in biomedical
research is: How do cells recognize and deal with misfolded proteins? My laboratory has taken a unique
approach to answering this question. Instead of studying protein aggregation in model organisms where proteins
readily aggregate, we have identified Dictyostelium discoideum (Dictyostelium) as a proteostatic outlier, highly
resistant to protein aggregation. Using this unique feature of Dictyostelium we are working to identify how nature
has dealt with the problem of protein aggregation. Once we determine the mechanisms Dictyostelium utilize to
suppress protein aggregation we plan to determine if this information can be used to develop therapeutic
strategies. In the next five years our goal is to have a comprehensive analysis of factors that suppress protein
aggregation in Dictyostelium. Factors that suppress protein aggregation in Dictyostelium will then be tested to
determine if they can be used to treat human diseases caused by protein aggregation. In addition to our work
on identifying how Dictyostelium evades protein aggregation we are also interested in what biological role
pathways that suppress protein aggregation play in Dictyostelium biology. One particular area of interest is in
Dictyostelium’s developmental cycle where single cellular amoeba transition to multicellular fruiting body. This
developmental cycle is of interest because the initial gene that we identified as a suppressor of protein
aggregation is part of a large gene family found only in Dictyostelium discoideum and Dictyostelium purpureum,
two closely related organisms that undergo this developmental process. This gene family is developmentally
regulated with most genes being transcribed in short bursts at time points during and after Dictyostelium
becomes multicellular. In the coming years we want to understand what role this protein family plays in
Dictyostelium development to determine if suppression of protein aggregation plays a critical role in Dictyostelium
development.

## Key facts

- **NIH application ID:** 10330643
- **Project number:** 2R35GM119544-07
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Kenneth Matthew Scaglione
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $402,500
- **Award type:** 2
- **Project period:** 2016-07-15 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330643

## Citation

> US National Institutes of Health, RePORTER application 10330643, Investigation into protein quality control pathways in Dictyostelium discoideum (2R35GM119544-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10330643. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*