Physics & Astronomy ETDs

Publication Date

Summer 7-31-2021

Abstract

Candida spp. pathogens continue to be a significant health care burden with high mortality and exceeding enormous healthcare costs. Candida infection range varies from dermatological infection to more severe bloodstream infection in debilitated patients. Due to this, research dedicated to understanding biophysical interactions between Candida species and the host’s immune cells is essential. The C-type lectin’s (CtLs) are known to bind to Candida cell walls and play a crucial role in downstream immune signaling. It is known that β-glucans, the highly immunogenic polysaccharide in Candida’s cell wall, are mostly masked underneath a layer of mannosylated proteins. The amount of β-glucan exposed to the cell wall is correlated to innate immune responses. This body of work addresses the mechanisms and functional significance of Dectin-1 nanoscale assembly in cellular membranes. We looked into the impact of glucan-bearing nanostructure size on their ability to activate Dectin-1 receptor signaling and associated effector responses by developing a method to mimic the yeast cell wall. We used direct Stochastic Optical Reconstruction Microscopy (dSTORM) to study the aggregation of receptors before and after stimulation with MMW glucan. We detected no significant change in singlet objects' density or multiple object clusters before vs. after MMW glucan stimulation. Also, we created a computational model to predict collisional FRET interactions at a level consistent with our FRET observations in resting cells. Furthermore, we showed that lysosomal exocytosis in response Dectin-1 engagement by fungi, which may represent a new type of anti-fungal effector response that deserves further exploration.


Degree Name

Physics

Level of Degree

Doctoral

Department Name

Physics & Astronomy

First Committee Member (Chair)

Aaron K Neumann

Second Committee Member

Keith Lidke

Third Committee Member

Diane S Lidke

Fourth Committee Member

David Dunlap

Keywords

Candida albicans, β-glucan, Dectin-1, Cell wall, Nanofabrication, FRET

Document Type

Dissertation

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