ORCID
https://orcid.org/0000-0002-3697-0565
Date of Award
Winter 12-14-2024
Degree Name
Master of Arts (AM/MA)
Degree Type
Thesis
Abstract
The causes of neurodegenerative disorders have long been of interest, and recent findings have pointed to these disorders beginning outside of the brain in other parts of the body. Connections between the brain and the gut have been postulated as a possible way in which amyloid aggregation observed in neurodegeneration can begin or occur. In this work, we aim to study the idea of cross seeding between bacterial amyloid proteins and human amyloid proteins in a yeast model to explore the phenotypes, properties and cross seeding capabilities of these proteins in-vivo.
A background on neurodegeneration, bacterial amyloids and cross seeding is first presented to give understanding on amyloids and nature of the cross-seeding hypothesis. Next, the development and/or use of yeast model systems for the study of CsgB and PSM bacterial amyloid proteins from Escherichia coli and Staphylococcus aureus respectively. The toxicity of the proteins as well as their aggregated phenotype in the yeast is discussed for CsgB first, followed by testing it in yeast models expressing neurodegenerative yeast proteins. After establishing its possible colocalization capabilities alongside š¯›¼-synuclein, the same experiments were repeated with PSMš¯›¼ and PSMĪ² proteins, showing increased toxicity in the presence of neurodegenerative proteins as well as aggregated puncta that co-localized alongside š¯›¼-synuclein. Overall, the work shown demonstrates the potential that yeast models have as a higher-throughput method for the study of bacterial amyloid proteins in-vivo.
Language
English (en)
Chair and Committee
Professor Timothy Wencewicz
Committee Members
Professor Meredith Jackrel (Advisor) Professor Courtney Reichhardt
Recommended Citation
Jayatilaka, Avika, "Studying Bacterial Amyloid Proteins Through a Yeast Model System" (2024). Arts & Sciences Electronic Theses and Dissertations. 3444.
https://openscholarship.wustl.edu/art_sci_etds/3444