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    Mechanisms of Prion Variant Competition

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    Author
    Norton, Jennifer Diane
    Issue Date
    2017
    Advisor
    Serio, Tricia
    
    Metadata
    Show full item record
    Publisher
    The University of Arizona.
    Rights
    Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
    Abstract
    The assembly of some misfolded proteins into aggregates can cause dramatic changes in cellular phenotypes. In prion diseases, these phenotypes are self-perpetuating because the highly ordered aggregates are capable of templating the conversion of soluble form of the protein into the aggregated form. Interestingly, the aggregated form of the protein can exist as a range of unique self-replicating conformations, referred to as prion "strains" or "variants," conferring distinct phenotypic characteristics to their hosts. The presence of more than one prion variant has been implicated in the alteration of prion phenotypes, interspecies transmission and anti-prion drug-resistance. When more than one variant arises or is introduced into the same host, usually the faster replicating variant phenotypically dominates over slower replicating variants; however, this dominance is not absolute. Studies in mammals suggest that these outcomes are determined by competition between variants for the conversion of soluble protein. However, other steps in prion replication have not been thoroughly examined. In this study we show that prion variant dominance is indeed determined by competing for the conversion of soluble protein, but this advantage arises from other cell-based factors that influence prion biogenesis, such as fragmentation rates and the number of templates present within the cell.
    Type
    text
    Electronic Dissertation
    Degree Name
    Ph.D.
    Degree Level
    doctoral
    Degree Program
    Graduate College
    Molecular & Cellular Biology
    Degree Grantor
    University of Arizona
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