MOLECULAR INTERACTIONS OF NK CELL CYTOTOXIC GRANULE TRAFFICKING DURING ANTIFUNGAL ACTIVITY

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dc.contributor.advisorMody, Christoher H.
dc.contributor.authorMok, Adley Ching Ho
dc.contributor.committeememberPeters, Nathan
dc.contributor.committeememberGanguly, Anutosh
dc.date2025-06
dc.date.accessioned2024-12-09T21:35:41Z
dc.date.available2024-12-09T21:35:41Z
dc.date.issued2024-12-04
dc.description.abstractCryptococcus neoformans is a fungal pathogen that causes life-threatening meningitis and pneumonia, particularly in immunocompromised hosts. Natural Killer (NK) cells are critical in the host defence against this pathogen acting by contacting fungal cells and triggering cell death by releasing cytotoxic effector molecules. Movement and positioning of the granules to the membrane during this process involves mechanical steps wherein granules laden with the effector proteins traverse the microtubule tracks using motor proteins (kinesins and dyneins). However, granule trafficking in response to fungal cells differs from the movement of granules during NK cell killing of tumour cells. During the final stages of fungal killing, immediately before degranulation, the microtubule organizing centre is positioned some distance from the synapse with the fungal cell, and granules are positioned between the Microtubule Organising Center and synapse. I explored the possibility that a kinesin transports the granules to the plasma membrane before release. I found that kinesin-1 is expressed in NK cells and kinesin-1 is required for granules to polarize and maintain its polarized position for degranulation against C. neoformans. This unique granule trafficking mechanism in response to fungal cells suggests a specialized adaptation for antifungal immunity. The positioning of granules between the Microtubule Organizing Center and the synapse may allow for more precise targeting and efficient release of antifungal agents. The identification of kinesin-1 as a key player in this process provides valuable insight into the molecular machinery underlying NK cell-mediated fungal killing.
dc.identifier.citationMok, A. (2024). Molecular interactions of NK cell cytotoxic granule trafficking during antifungal activity (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.urihttps://hdl.handle.net/1880/120172
dc.language.isoen
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgary
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.subjectNatural Killer Cells
dc.subjectHost-Pathogen Interactions
dc.subjectCryptococcus
dc.subjectKinesins
dc.subject.classificationImmunology
dc.subject.classificationBiophysics--Medical
dc.titleMOLECULAR INTERACTIONS OF NK CELL CYTOTOXIC GRANULE TRAFFICKING DURING ANTIFUNGAL ACTIVITY
dc.typemaster thesis
thesis.degree.disciplineMedicine – Immunology
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
ucalgary.thesis.accesssetbystudentI do not require a thesis withhold – my thesis will have open access and can be viewed and downloaded publicly as soon as possible.
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