{"id":{"repo_id":"creighton","oai_identifier":"oai:cdr.creighton.edu:10504/134660"},"canonical_url":"https://search.dev.ndltd.org/etd/creighton/oai:cdr.creighton.edu:10504/134660","repository":{"repo_id":"creighton","name":"Creighton University","base_url":"https://cdr.creighton.edu/server/oai/request"},"display":{"title":"Prions Propagate as Dynamic Strain Mixtures","abstract":"Prions are the agent responsible for a group of transmissible and inevitably fatal neurodegenerative disease in humans and other mammals. Prion disease is caused by the misfolding of a host encoded protein, PrPC, into the infectious conformation PrPSc. Phenotypic differences in disease (i.e., strains) have been observed for decades and are thought to be encoded by stain-specific conformations of PrPSc. There is evidence that prion strains exist as a mixture of multiple strains, containing a dominant strain, which is responsible for the phenotype, and suppressed populations of substrains. However, direct evidence for the presence of substrains has been difficult to establish, due in part to strain interference and limited detection methods. It is hypothesized that prions propagate as dynamic strain mixtures. Utilizing experimentally feasible methods, we provide evidence for prions consisting of a dominant strain and substrains. We show that the improved sensitivity of the in vitro amplification method called protein misfolding cyclic amplification (PMCA) allows for detection of minute quantities of PrPSc. Combined with differences in conformational stability between strains which allow for the selective amplification and detection of biochemically distinct substrains. There are important implications for stains existing as mixtures. Namely, increased zoonotic disease potential, and the possible emergence of drug resistant prions with the use of targeted anti-prion agents. These data inform our understanding of prions and the zoonotic potential for disease and prion adaptation in the presence of anti-prion drugs. Overall, these investigations improve our understanding of the dynamic nature of prion strains.","abstract_html":"Prions are the agent responsible for a group of transmissible and inevitably fatal neurodegenerative disease in humans and other mammals. Prion disease is caused by the misfolding of a host encoded protein, PrPC, into the infectious conformation PrPSc. Phenotypic differences in disease (i.e., strains) have been observed for decades and are thought to be encoded by stain-specific conformations of PrPSc. There is evidence that prion strains exist as a mixture of multiple strains, containing a dominant strain, which is responsible for the phenotype, and suppressed populations of substrains. However, direct evidence for the presence of substrains has been difficult to establish, due in part to strain interference and limited detection methods. It is hypothesized that prions propagate as dynamic strain mixtures. Utilizing experimentally feasible methods, we provide evidence for prions consisting of a dominant strain and substrains. We show that the improved sensitivity of the in vitro amplification method called protein misfolding cyclic amplification (PMCA) allows for detection of minute quantities of PrPSc. Combined with differences in conformational stability between strains which allow for the selective amplification and detection of biochemically distinct substrains. There are important implications for stains existing as mixtures. Namely, increased zoonotic disease potential, and the possible emergence of drug resistant prions with the use of targeted anti-prion agents. These data inform our understanding of prions and the zoonotic potential for disease and prion adaptation in the presence of anti-prion drugs. Overall, these investigations improve our understanding of the dynamic nature of prion strains.","abstract_has_math":false,"creators":["Gunnels, Tess"],"institution":"Creighton University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Bartz, Jason"],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021-12-02","date_published":"2021-12-02","updated_at":"2026-07-24T01:50:57Z","subjects":[],"languages":["en_US"],"rights":["Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10504/134660","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Bartz, Jason"]},{"key":"dc:creator","label":"Author","values":["Gunnels, Tess"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2021-12-09T23:28:40Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2021-12-09T23:28:40Z"]},{"key":"dc:date.issued","label":"Date","values":["2021-12-02"]},{"key":"dc:publisher","label":"Institution","values":["Creighton University"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_US"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10504/134660"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Prions are the agent responsible for a group of transmissible and inevitably fatal neurodegenerative disease in humans and other mammals. Prion disease is caused by the misfolding of a host encoded protein, PrPC, into the infectious conformation PrPSc. Phenotypic differences in disease (i.e., strains) have been observed for decades and are thought to be encoded by stain-specific conformations of PrPSc. There is evidence that prion strains exist as a mixture of multiple strains, containing a dominant strain, which is responsible for the phenotype, and suppressed populations of substrains. However, direct evidence for the presence of substrains has been difficult to establish, due in part to strain interference and limited detection methods. It is hypothesized that prions propagate as dynamic strain mixtures. Utilizing experimentally feasible methods, we provide evidence for prions consisting of a dominant strain and substrains. We show that the improved sensitivity of the in vitro amplification method called protein misfolding cyclic amplification (PMCA) allows for detection of minute quantities of PrPSc. Combined with differences in conformational stability between strains which allow for the selective amplification and detection of biochemically distinct substrains. There are important implications for stains existing as mixtures. Namely, increased zoonotic disease potential, and the possible emergence of drug resistant prions with the use of targeted anti-prion agents. These data inform our understanding of prions and the zoonotic potential for disease and prion adaptation in the presence of anti-prion drugs. Overall, these investigations improve our understanding of the dynamic nature of prion strains."]},{"key":"dc:title","label":"Title","values":["Prions Propagate as Dynamic Strain Mixtures"]}]}],"canonical_facts":{"dc:contributor.advisor":["Bartz, Jason"],"dc:creator":["Gunnels, Tess"],"dc:date.accessioned":["2021-12-09T23:28:40Z"],"dc:date.available":["2021-12-09T23:28:40Z"],"dc:date.issued":["2021-12-02"],"dc:description.abstract":["Prions are the agent responsible for a group of transmissible and inevitably fatal neurodegenerative disease in humans and other mammals. Prion disease is caused by the misfolding of a host encoded protein, PrPC, into the infectious conformation PrPSc. Phenotypic differences in disease (i.e., strains) have been observed for decades and are thought to be encoded by stain-specific conformations of PrPSc. There is evidence that prion strains exist as a mixture of multiple strains, containing a dominant strain, which is responsible for the phenotype, and suppressed populations of substrains. However, direct evidence for the presence of substrains has been difficult to establish, due in part to strain interference and limited detection methods. It is hypothesized that prions propagate as dynamic strain mixtures. Utilizing experimentally feasible methods, we provide evidence for prions consisting of a dominant strain and substrains. We show that the improved sensitivity of the in vitro amplification method called protein misfolding cyclic amplification (PMCA) allows for detection of minute quantities of PrPSc. Combined with differences in conformational stability between strains which allow for the selective amplification and detection of biochemically distinct substrains. There are important implications for stains existing as mixtures. Namely, increased zoonotic disease potential, and the possible emergence of drug resistant prions with the use of targeted anti-prion agents. These data inform our understanding of prions and the zoonotic potential for disease and prion adaptation in the presence of anti-prion drugs. Overall, these investigations improve our understanding of the dynamic nature of prion strains."],"dc:identifier.uri":["http://hdl.handle.net/10504/134660"],"dc:language.iso":["en_US"],"dc:publisher":["Creighton University"],"dc:rights":["Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above."],"dc:title":["Prions Propagate as Dynamic Strain Mixtures"],"dc:type":["Dissertation"]},"updated_at":"2026-07-24T01:50:57Z"}