Examining the Role of Non-Canonical NOD-like Receptors and Inflammasomes in Inflammation and Disease

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dc.contributor.advisorMuruve, Daniel A.
dc.contributor.authorPlatnich, Jaye Matthew
dc.contributor.committeememberMacDonald, Justin Anthony
dc.contributor.committeememberPower, Christopher
dc.contributor.committeememberDuff, Henry J.
dc.contributor.committeememberPeters, Nathan C.
dc.date.accessioned2018-04-04T14:16:43Z
dc.date.available2018-04-04T14:16:43Z
dc.date.issued2018-03-21
dc.description.abstractThe NOD-like Receptors (NLRs) are a family of pattern recognition receptors known to regulate a variety of immune signaling pathways. A substantial portion of NLR research focuses on the pyrin domain-containing NLRP subfamily. The canonical NLRPs are inflammasome-forming proteins responsible for the activation of caspase-1 and the maturation and secretion of the pro-inflammatory cytokines IL-1β and IL-18. In contrast, the non-canonical inflammasome-independent NLRPs regulate a variety of other pathways, including MAPK and NF-κB, through the formation of non-inflammasome complexes. Interestingly, not all inflammasomes are nucleated by NLRPs. The recently characterized non-canonical caspase-4 (caspase-11 in mice) inflammasome is known to be a key driver of the innate immune response to intracellular pathogens (and the molecules associated with them), by triggering both inflammatory cell death and the activation of canonical inflammasomes. At the outset of this PhD work, the understanding of both non-inflammasome-forming NLRPs and the non-canonical caspase-4 inflammasome was poor and the studies were sparse. It was the goal of this thesis to characterize the expression, gene regulation, and function of the non-inflammasome-forming NLR protein NLRP6, both at the cellular and biochemical level. Furthermore, using a pathogen-associated molecular pattern (PAMP)-driven model of inflammation, we sought to elucidate the function of the non-canonical caspase-4 inflammasome, particularly as it pertains to the regulation of the canonical inflammasome and cell death. By studying the fundamental biology underlying these lesser-known mediators of the innate immune system, we hoped to better understand their contribution to the early immune response and their role in driving inflammatory disease with a view to, one day, ameliorating the condition of patients suffering from these afflictions through the development of targeted therapeutics.en_US
dc.identifier.citationPlatnich, J. M. (2018). Examining the Role of Non-Canonical NOD-like Receptors and Inflammasomes in Inflammation and Disease (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/31757en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/31757
dc.identifier.urihttp://hdl.handle.net/1880/106465
dc.language.isoeng
dc.publisher.facultyCumming School of Medicine
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectinflammasome
dc.subjectNLRP6
dc.subjectInflammation
dc.subjectKidney disease
dc.subjectShiga toxin
dc.subjectNLRP3
dc.subjectMacrophage
dc.subjectNLR
dc.subjectCell death
dc.subjectPyroptosis
dc.subjectCaspase
dc.subjectATPase
dc.subject.classificationBiologyen_US
dc.subject.classificationMicrobiologyen_US
dc.subject.classificationPhysiologyen_US
dc.subject.classificationImmunologyen_US
dc.subject.classificationMedicine and Surgeryen_US
dc.titleExamining the Role of Non-Canonical NOD-like Receptors and Inflammasomes in Inflammation and Disease
dc.typedoctoral thesis
thesis.degree.disciplineImmunology
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
ucalgary.thesis.checklistI confirm that I have submitted all of the required forms to Faculty of Graduate Studies.en_US
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