# Nucleic Acids Roles in Protein Folding and Aggregation

> **NIH NIH R35** · UNIVERSITY OF DENVER (COLORADO SEMINARY) · 2021 · $368,289

## Abstract

PROJECT SUMMARY
This project is to investigate how nucleic acids are involved in protein aggregation and folding. Protein
misfolding and aggregation lead to many debilitating diseases including Alzheimer’s disease. We recently
found that nucleic acids can have strong chaperone activity to prevent protein aggregation and aid protein
folding. Given their preponderance in the cell and strong effects on protein folding and aggregation, it is highly
likely that nucleic acids are important players in protein homeostasis. The work described in this proposal lays
out studies to provide our first understanding of the basic principles by which nucleic acids modulate protein
folding and aggregation, and thus protein homeostasis.
Our current investigations are directed at addressing two critical aspects: 1) Understanding the roles of
chaperone nucleic acids in the cell, and 2) Understanding the molecular mechanism of chaperone nucleic
acids. These studies utilize an interdisciplinary approach combining molecular biology, biochemistry,
biophysics, and bacterial genetics.
Our preliminary data indicates that both the activities of nucleic acids to prevent and promote oligomerization
are highly sequence dependent, and are especially encoded for by quadruplex structures. These results help
explain the biophysical causes of several neurodegenerative diseases. This insight also gives us the
opportunity to control and study protein aggregation using specific nucleic acid sequences and structures. Our
preliminary data also indicates that quadruplex-containing chaperone sequences are also effective at
improving the folding environment in E. coli. We are currently expanding these studies to known quadruplex
structures with chaperone-like effects in the cell, and investigating the structural basis of chaperone activity.
Together, these studies will lay the foundation for a new understanding of protein homeostasis and how it
relates to nucleic acid biology. This information will be critical in the future to help combat myriad protein
misfolding and aggregation diseases.

## Key facts

- **NIH application ID:** 10270767
- **Project number:** 1R35GM142442-01
- **Recipient organization:** UNIVERSITY OF DENVER (COLORADO SEMINARY)
- **Principal Investigator:** Scott Andrew Horowitz
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $368,289
- **Award type:** 1
- **Project period:** 2021-09-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10270767

## Citation

> US National Institutes of Health, RePORTER application 10270767, Nucleic Acids Roles in Protein Folding and Aggregation (1R35GM142442-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10270767. Licensed CC0.

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