Computational Model of Prion Protein Functions: The good, the bad and the ugly

Document Type

Oral Presentation

Campus where you would like to present

Ellensburg

Event Website

https://digitalcommons.cwu.edu/source

Start Date

15-5-2019

End Date

15-5-2019

Abstract

The word prion stands for proteinaceous infectious particle, and is most infamous with respect to the Mad Cow Disease scare of the 1990’s. Prions are typically concentrated in the brain, and are responsible for most fatal neurodegenerative diseases, including Alzheimer’s, Jakob-Creutzfeldt Disease, and Huntingtons. Recent research shows that prions are also fundamental to how connections are made within the brain, playing a role in growth cone guidance and in the formation of memories. The central goal of this research project is to computationally investigate this schism in prion behavior. To explore the infectious nature of prions, a cell environment was modeled in which prions were free to undergo Brownian motion, while stochastically transitioning to an infected state. Infected prions that encountered one another could join together to form a larger aggregate. The level of aggregation was shown to grow rapidly before plateauing as the available concentration of prions decreases. The initial model was modified to include a nucleation step, in which large aggregates spontaneously break into smaller infectious fragments. Simulations demonstrated that the time scale for total cell infection is sensitive to the threshold for nucleation. To explore the beneficial side of prions, a model for prion stimulation of axonal outgrowth was developed, based on the hypothesis that prions stimulate movement of growth cones, which are structures at the tips of axons that guide axonal growth during nervous system development. Two distinct mechanisms for the interactions between prions and growth cones were simulated, making testable predictions that can be compared against experimental data.

Faculty Mentor(s)

Erin Craig

Department/Program

Physics

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May 15th, 2:00 PM May 15th, 3:15 PM

Computational Model of Prion Protein Functions: The good, the bad and the ugly

Ellensburg

The word prion stands for proteinaceous infectious particle, and is most infamous with respect to the Mad Cow Disease scare of the 1990’s. Prions are typically concentrated in the brain, and are responsible for most fatal neurodegenerative diseases, including Alzheimer’s, Jakob-Creutzfeldt Disease, and Huntingtons. Recent research shows that prions are also fundamental to how connections are made within the brain, playing a role in growth cone guidance and in the formation of memories. The central goal of this research project is to computationally investigate this schism in prion behavior. To explore the infectious nature of prions, a cell environment was modeled in which prions were free to undergo Brownian motion, while stochastically transitioning to an infected state. Infected prions that encountered one another could join together to form a larger aggregate. The level of aggregation was shown to grow rapidly before plateauing as the available concentration of prions decreases. The initial model was modified to include a nucleation step, in which large aggregates spontaneously break into smaller infectious fragments. Simulations demonstrated that the time scale for total cell infection is sensitive to the threshold for nucleation. To explore the beneficial side of prions, a model for prion stimulation of axonal outgrowth was developed, based on the hypothesis that prions stimulate movement of growth cones, which are structures at the tips of axons that guide axonal growth during nervous system development. Two distinct mechanisms for the interactions between prions and growth cones were simulated, making testable predictions that can be compared against experimental data.

https://digitalcommons.cwu.edu/source/2019/Oralpres/56