# Dissecting the Mechanism of Prion Formation with a Permissive Host

> **NIH NIH R01** · DARTMOUTH COLLEGE · 2021 · $555,038

## Abstract

Project Summary
Prion diseases are infectious neurodegenerative diseases caused by the induced
conformational change of a host-encoded glycoprotein, PrPC, into a pathogenic
conformer, PrPSc. Currently, there are no vaccines or therapies available for these
invariably fatal diseases, primarily because we do not understand the mechanism of
PrPSc formation.
Interestingly, there are large differences in host susceptibility to prion infection between
different animal species. For instance, rabbits appear to be resistant to all prion strains,
while bank voles appear to be a universal host. This variation, which is dependent on
PrP sequence, provides us with a unique opportunity to identify the key steps in PrPSc
formation shared by all species. Using rigorous biochemical tools developed in our
laboratory, we will exploit these naturally occurring differences in host susceptibility to
dissect the mechanism of prion replication. Specifically, this powerful comparative
biochemistry approach will be used to accomplish the following aims:
1. Directly test the protein-only hypothesis of prion infectivity.
2. Identify and characterize PrPC domains that control susceptibility to prion conversion.
3. Determine whether cofactor molecules and post-translational modifications restrict
the host range of prion infection.
The results of this project will greatly advance our understanding of the prion replication
mechanism. They will also impact our understanding of related, prion-like diseases,
such as Alzheimer's and Parkinson's disease.

## Key facts

- **NIH application ID:** 10136732
- **Project number:** 5R01NS102301-04
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Surachai Supattapone
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $555,038
- **Award type:** 5
- **Project period:** 2018-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136732

## Citation

> US National Institutes of Health, RePORTER application 10136732, Dissecting the Mechanism of Prion Formation with a Permissive Host (5R01NS102301-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10136732. Licensed CC0.

---

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