# A model system for pathological transitions of RNA-binding protein aggregates

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $226,293

## Abstract

Project Summary/Abstract
Age-related neurodegenerative diseases are a class of incurable diseases that result in the progressive
degeneration of neuronal cells. Recent research has pointed to a role for RNA-binding proteins in age-
related neurodegenerative diseases: as many RNA-binding proteins have aggregation-prone
intrinsically disordered regions, they accumulate in pathological inclusions of various
neurodegenerative diseases, and mutations in a number of RNA-binding proteins have been linked to
neurodegenerative diseases. For many RNA-binding proteins linked to neurodegenerative diseases
they also become concentrated into mRNP granules during stressful conditions. This formation of
mRNP granules during stress is beneficial to cells, as disruption of these granules sensitizes cells to a
variety of stressors. Our hypothesis is that mRNP granules initially form as non-toxic, potentially
beneficial structures during the aging process, but that they undergo a pathological transition that leads
to cell death. This proposal seeks to establish a model system for this pathological transition using
yeast in combination with microfluidics to follow the formation and transition of mRNP granules during
aging. To accomplish this, we will (Aim 1) build on our preliminary data exploring the pathogenicity of
large age-induced mRNP granules using microfluidics and fluorescent microscopy to follow single yeast
cells across their entire lifespan. Secondly, we will (Aim 2) identify markers for this pathological
transition by measuring changes in the material state and macromolecular composition of age-induced
mRNP granules. In the long term these markers will help to elucidate the mechanistic details of this
transition. Together this system will establish a new paradigm to understand basic details on how
mRNP granules can transition from non-toxic, potentially beneficial structures to pathological inclusions
that drive the degeneration of cells. As many genes and pathways are conserved from yeast to
mammals, including pathways that affect aging, this research may point to new targets to help
ameliorate neurodegenerative diseases in humans.

## Key facts

- **NIH application ID:** 9979108
- **Project number:** 1R21AG064342-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Brian Matthew Zid
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $226,293
- **Award type:** 1
- **Project period:** 2020-09-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979108

## Citation

> US National Institutes of Health, RePORTER application 9979108, A model system for pathological transitions of RNA-binding protein aggregates (1R21AG064342-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9979108. Licensed CC0.

---

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