# Functional and Pathological Assembly of Prion-like Domains

> **NIH NIH R35** · COLORADO STATE UNIVERSITY · 2024 · $417,346

## Abstract

PROJECT SUMMARY
Hundreds of human proteins contain prion-like domains (PrLDs), defined as protein domains that are
compositionally similar to yeast prion domains. In recent years, a growing number of PrLDs in various
organisms have been shown to form functional assemblies that regulate various cellular activities. These
assemblies vary in both complexity and material states, from highly stable amyloid aggregates that can act as
a form of cellular memory to complex, reversible biomolecular condensates such as stress granules.
Additionally, mutations in PrLDs have been linked to various degenerative disorders, including amyotrophic
lateral sclerosis and frontotemporal dementia. Disease-associated mutations tend to increase the aggregation
propensity of the PrLDs. This observation has led to the hypothesis that many PrLDs are designed to mediate
dynamic reversible interactions involved in cellular regulation, and that mutations alter the dynamics of these
assemblies, promote the conversion to more stable structures, or cause aberrant aggregation of the PrLDs.
However, while PrLDs are highly over-represented in eukaryotic genomes, the functions of only a small fraction
of PrLDs have been characterized. Our long-term goal is to develop a comprehensive understanding of the
roles of PrLDs in normal physiology and in disease. Towards this end, we are examining the basis for
recruitment of PrLDs to complex assemblies such as stress granules, examining how specificity of targeting is
achieved between different assemblies, and characterizing novel functions of these domains. Collectively,
these studies will provide a framework for understanding the diverse functions of PrLDs.

## Key facts

- **NIH application ID:** 10765242
- **Project number:** 2R35GM130352-06
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Eric D Ross
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $417,346
- **Award type:** 2
- **Project period:** 2019-02-01 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765242

## Citation

> US National Institutes of Health, RePORTER application 10765242, Functional and Pathological Assembly of Prion-like Domains (2R35GM130352-06). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10765242. Licensed CC0.

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