# Molecular mechanisms of prion and amyloid propagation

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2021 · $83,815

## Abstract

PROJECT SUMMARY FROM PARENT AWARD
Prion diseases are a group of transmissible neurodegenerative disorders that include Creutzfeldt-Jakob disease
and Gerstmann-Straussler-Scheinker (GSS) disease in humans, scrapie in sheep, bovine spongiform
encephalopathy (“mad cow disease”) in cattle and chronic wasting disease in cervids. The most intriguing aspect
of these disorders is the nature of the infectious prion pathogen that is believed to be a misfolded protein
aggregate with characteristics of an amyloid. However, the structure of these infectious protein particles remains
largely unknown. The overall objective of this project is to gain high-resolution structural insight into the
mechanism of prion propagation as well as the phenomena of prion strains and transmissibility barriers. To this
end, we use a model of amyloid fibrils generated from the C-terminally truncated prion protein PrP23-144, a
variant associated with the Y145Stop phenotype of a GSS-like disease. A unique advantage of this model is that
it is amenable to detailed structural characterization at atomic level by solid-state nuclear magnetic resonance
(NMR) spectroscopy and other biophysical techniques. Three interrelated specific aims are proposed. The first
aim is to determine the high-resolution structures for several different strains of mouse and Syrian hamster
PrP23-144 amyloid fibrils using solid-state NMR. In combination with the high-resolution structure of human
PrP23-144 amyloid already determined by us, these data will be used to gain insight into the structural basis of
PrP amyloid seeding specificities, an in vitro surrogate of transmissibility barriers. In the second aim, we will use
the PrP23-144 amyloid model to elucidate the poorly understood phenomenon of prion strain switching as well
as the mechanism of strain selection. Finally, the third aim seeks to determine high-resolution structures of PrP
amyloids associated with distinct phenotypes of GSS disease. The latter insight is of fundamental importance,
as no information is at present available regarding the structures of GSS-associated PrP amyloids or the
relationship between specific structural features and disease phenotype.

## Key facts

- **NIH application ID:** 10387124
- **Project number:** 3R01GM094357-08S1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Christopher P Jaroniec
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $83,815
- **Award type:** 3
- **Project period:** 2011-06-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10387124

## Citation

> US National Institutes of Health, RePORTER application 10387124, Molecular mechanisms of prion and amyloid propagation (3R01GM094357-08S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10387124. Licensed CC0.

---

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