Physical Chemistry seminar: Sabrina Leslie
Place: Lecturehall KC:H,I
Contact: emma [dot] sparr [at] fkem1 [dot] lu [dot] se
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A Physical Chemistry seminar byAssociate Professor Sabrina Leslie, UBC Department of Physics and Astronomy and Michael Smith Labs, Canada
Title: Single-molecule and single-cell microscopy of mRNA-lipid-nanoparticles: applying nanoscale physics to advance nanomedicines
Abstract: In response to the pandemic, new mRNA-LNP products were developed and injected into billions of human arms. Despite the success of these nanomedicines in suppressing the pandemic at the level of the population, at the level of the individual particle the efficiency of this product is approximately one percent. This presents an important opportunity for microscopists and therapeutic developers to work together to improve these products, as well as to leverage this new mRNA-LNP platform to create a vast array of new nanomedicines ranging from COVID19 vaccines to cancer treatments. In this talk, I will present a quantitative single-particle and single-cell imaging platform called CLiC (Convex Lens-induced Confinement) which we have developed and applied to fill important gaps in understanding and characterization of nanomedicines and thereby help make them better. CLiC imaging enables simultaneous single-particle measurements of multiple properties of mRNA LNPs, such as the distribution of size and mRNA-payload, as well as interaction rates in response to specific biomolecules or solution conditions. Importantly these single-particle measurements can be made in correlation with observations of their dynamic trajectories and interactions within cells. Our overall research, which is highly collaborative with the Cullis lab and members of the Nanomedicine Center for Excellence based at UBC, aims to characterize and understand the mechanisms of action of emerging classes of therapeutics and vaccines, so as to ultimately enable their optimization and come closer to addressing patients’ needs. For example, 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 and explore intracellular dynamics such as endosomal release, but in a controlled setting. Over the long term and in collaboration with health scientists, we are working towards correlating our 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 throughline of understanding of vaccine/drug effectiveness from the microscopic to clinical scale. This talk will begin with our publication in ACS Nano (Kamanzi et al, 2021), share results from two additional manuscripts in submission and preparation, and describe our ongoing collaboration with health scientists to better understand mRNA-LNP vaccines and medicines through new biophysical measurements. In visiting Sweden and establishing new connections after the pandemic, my team and I are very open to new collaborations and finding opportunities for impact together.