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PhD Transfer Seminar – Yuchen Hou (Treanor Lab)

April 12, 2021 @ 1:00 pm - 1:30 pm

Using DNA Nanotechnology to Investigate Antigen Organization Governing B cell Activation




B cells are integral members of the adaptive immune system. Upon activation, they differentiate into antibody-secreting plasma cells, making them the targets of vaccination. However, aberrant activation results in the secretion of self-reactive antibodies that contribute to autoimmunity, with targeted therapeutics remaining an unmet need. B cell activation is initiated by the binding of pathogen components called antigens to B cell receptors (BCRs), leading to the formation of signalosomes to drive cellular responses. The nature of antigen is critical in this process. For example, antigens with repetitive binding sites induce strong antibody responses, and high densities of otherwise non-stimulatory self-antigens can trigger B cell activation. However, the exact requirements of the nanoscale organization of antigen remain poorly characterized. Furthermore, the existence of BCRs in nanoclusters raises important questions regarding how antigen arrays associate with receptor nanoclusters to trigger activation. To address this gap in knowledge, we are collaborating with the Chou Lab (IBBME, UofT) to design a DNA origami platform compatible with our planar lipid bilayer system for displaying ligands with programmable spacings and valency. This will mimic membrane-bound antigen encounter in vivo. We found that origami adsorption and mobility on phosphocholine-based bilayers are facilitated by divalent cations and cholesterol. Using total internal reflection fluorescence microscopy, we confirmed that antigen-functionalized, membrane-associated platforms can stimulate B cells. We will continue developing this design to manipulate BCR triggering through defined antigen arrays alone and together with inhibitory ligands to selectively inhibit antigen-specific B cells. This project will provide structural guidelines for the development of nanostructured vaccines and targeted therapeutics for B-cell mediated autoimmunity.



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Monday, April 12th, 2021 @ 1:00pm



April 12, 2021
1:00 pm - 1:30 pm