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Sabrina Leslie: Single-molecule microscopy of RNA-lipid-nanoparticles: Bringing the nanoscale physics to help advance nanomedicines
September 15 @ 10:00 am - 11:00 am
Sabrina Leslie: Associate Professor, UBC Department of Physics and Astronomy and Michael Smith Labs
Affiliate Faculty member, SBME, GSAT, BIONF
Abstract: I will present a unique quantitative single-particle imaging platform called CLiC (Convex Lens-induced Confinement) which enables simultaneous measurements of the size, mRNA-payload, and dynamic properties of vaccine and other nanoparticles in controlled, cell-like conditions (Kamanzi et al, ACS Nano 2021). Recently relocated to UBC PHAS and MSL from McGill in 2021, our nanoparticle imaging team innovates nanoscale devices and approaches to investigate the structure-activity relationships which can help characterize and understand emerging classes of mRNA-lipid-nanoparticles such as COVID19 vaccines. We image individual confined, freely diffusing particles in solution as well as during reagent-exchange, such as in response to a change in solution pH, in order to emulate/explore intracellular dynamics in a controlled setting. Over the long term and in collaboration with health/therapeutic scientists, we are working towards correlating detailed multi-scale data sets, including single-particle measurements made in vitro as well as in cells and tissues, with clinical results, to create a through-line of understanding of vaccine/drug effectiveness from the microscopic to clinical scale. Our inspiration is to innovate and use nanoscale tools to obtain new biophysical insights into how and why medicines work to enable and optimize their rational design and engineering. This talk builds off our recent publication in ACS Nano (Kamanzi et al, 2021), describes our ongoing collaboration with the Cullis laboratory and others (UBC Health Sciences), and shares an outlook including opportunities for new PHAS and interdisciplinary graduate students at UBC looking to join an exciting interdisciplinary team of biophysicists. The Leslie Lab has recently set up its new laboratory at MSL/NCE with several state-of-the-art microscopes and we are excited to share our work with QMI and get to know our new community through and after this seminar.
Caption: CLiC single-particle imaging and analysis of Lipid Nanoparticles (LNPs) enables characterization of detailed size and loading distributions of RNA–LNP complexes. A) Compressing the flow-cell confines LNPs for extended study. B) Trapped LNPs are shown in microwells. 100s – 1000s of isolated LNPs are imaged in parallel, a process which can be repeated thousands of times. C) Single-particle tracking is used to obtain LNP trajectories, which are then used to obtain particle diffusivity/ size (D) as well as intensity/RNA payload (E). This information is then used to define LNP size and RNA payload distributions and inform structure-activity relationships of the nanoparticles in conjunction with other dynamic, multi-scale and biological data.