# Structural transformations of dementia-related proteins: droplets, gels and amyloids

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $413,431

## Abstract

Project summary
Several proteins related to Alzheimer’s disease and other dementias are known to undergo liquid-liquid phase
separation, a process that may be essential for their function. At the same time, such proteins are often known
to form amyloid fibrils and deposits in the brains of patients suffering from those conditions. The molecular
connection between these processes is unclear and may involve an intermediate gelation step. Illuminating the
properties of gels in molecular detail has been difficult due to their viscous, dynamic and heterogeneous
nature. Here, we propose to develop a solid-state nuclear magnetic resonance (NMR) approach that can
characterize the transformations of such proteins from the droplet to the gel and amyloid states in the same
sample and in real time. Our goal is to characterize the elusive interactions that build the gel networks and to
capture the dramatic transformations that proteins must undergo from the intrinsically disordered state to the β-
sheet rich amyloid form. This information will be essential in understanding the relationship between normal
protein function and disease and to develop effective therapies, diagnostic tools and interventions. We will test
and optimize our approach with the fused in sarcoma (FUS) protein. FUS is associated with frontotemporal
dementia (FTD) and amyotrophic lateral sclerosis (ALS) and has a well characterized phase separation
behavior that includes the formation of liquid droplets, gels and amyloids. Using our approach, we aim to
provide a molecular description of these transformations. Furthermore, we propose to use our strategy to
evaluate the influence of biologically relevant components such as RNA on these processes. Our approach is
easily adaptable to other dementia-related proteins and we envision that it will become a powerful molecular
tool in illuminating protein behavior in health and disease.

## Key facts

- **NIH application ID:** 10055682
- **Project number:** 1R21AG069064-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Galia Debelouchina
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $413,431
- **Award type:** 1
- **Project period:** 2020-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10055682

## Citation

> US National Institutes of Health, RePORTER application 10055682, Structural transformations of dementia-related proteins: droplets, gels and amyloids (1R21AG069064-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10055682. Licensed CC0.

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