Sabrina Leslie
Department of Physics, McGill University
Deconstructing biology with simple single-molecule imaging: Controlling conformation, confinement, and concentration
Abstract: The past decade of advances in molecular biology has revealed that the cell comprises a complex system of networks on the scale of atoms, molecules, and organelles. The next breakthroughs in life science research, in academic labs and as applied to drug development, and other translational disciplines, will depend on the ability of physicists and engineers to unravel the complex biophysical phenomena that underlie cellular function with greater resolution. Most currently available technologies rely on ensemble population measurements which frustrate the absolute quantitation which is required to reveal the true complexity of life at the molecular scale. In this talk, I will introduce Convex Lens-induced Confinement (CLiC) microscopy, a general method to image molecular interactions one molecule at a time, while emulating ‘cell like’ conditions, with precision and control. Because it mechanically confines molecules in the field of view, CLiC eliminates the need to ‘tether’ molecules thereby avoiding the complexity and potential biases. By visualizing the individual trajectories of many molecules at once, and for long time periods, CLiC allows us to investigate important biophysical questions about molecular behaviour. In this talk, I will present our recent CLiC experiments which elucidate how higher-order DNA structures can regulate the dynamic unwinding of specific target sites within a crowded environment, and the kinetics of binding to these sites (Scott et. al,, NAR 2018 and BIORXIV/2019/591008). Beyond discussing new insights from CLiC into the statistical mechanics of DNA and structure-mediated interactions, I will discuss key applications of our work in drug development, including visualizing protein aggregation, nanoparticle dynamics, and CRISPR-Cas9 targeting dynamics.
Abstract: The past decade of advances in molecular biology has revealed that the cell comprises a complex system of networks on the scale of atoms, molecules, and organelles. The next breakthroughs in life science research, in academic labs and as applied to drug development, and other translational disciplines, will depend on the ability of physicists and engineers to unravel the complex biophysical phenomena that underlie cellular function with greater resolution. Most currently available technologies rely on ensemble population measurements which frustrate the absolute quantitation which is required to reveal the true complexity of life at the molecular scale. In this talk, I will introduce Convex Lens-induced Confinement (CLiC) microscopy, a general method to image molecular interactions one molecule at a time, while emulating ‘cell like’ conditions, with precision and control. Because it mechanically confines molecules in the field of view, CLiC eliminates the need to ‘tether’ molecules thereby avoiding the complexity and potential biases. By visualizing the individual trajectories of many molecules at once, and for long time periods, CLiC allows us to investigate important biophysical questions about molecular behaviour. In this talk, I will present our recent CLiC experiments which elucidate how higher-order DNA structures can regulate the dynamic unwinding of specific target sites within a crowded environment, and the kinetics of binding to these sites (Scott et. al,, NAR 2018 and BIORXIV/2019/591008). Beyond discussing new insights from CLiC into the statistical mechanics of DNA and structure-mediated interactions, I will discuss key applications of our work in drug development, including visualizing protein aggregation, nanoparticle dynamics, and CRISPR-Cas9 targeting dynamics.
Biography
Sabrina Leslie's academic training began in 1998 as an undergraduate at UBC, where she graduated from the Honours Physics and Mathematics Program as a Canada Scholar and recipient of the CK Choi Presidential Award. In 2002, She moved to UC Berkeley as an NSERC fellow to pursue doctoral studies in optical and atomic physics. Under the guidance of Dr. Dan Stamper-Kurn, She pioneered imaging experiments of disorder-to-order transitions of atomic vapours held in optical traps. In 2009, she made a significant transition, from visualizing atoms in vacuum chambers, to visualizing biomolecules in liquids; a transition by a desire to get a little closer to life in her research. This transition to the Department of Chemistry and Chemical Biology at Harvard University was made possible with a Mary Fieser post-doctoral fellowship, with the mandate to explore this inspiration. At Harvard, she invented a single-molecule imaging technology called Convex Lens-induced Confinement (CLiC), which established her as a pioneer in single-molecule investigations with a range of applications. In 2012, she became an Assistant Professor at McGill University and founded her research group. Professor Leslie has developed CLiC into a platform technology and used it for new studies of nucleic acids, proteins, polymers, nanomaterials, biologics, cells, etc. To expand and commercialize her technology and key applications, she co-founded a start-up company ScopeSys, with a technical and business team based in Canada.
Group website
Sabrina Leslie's academic training began in 1998 as an undergraduate at UBC, where she graduated from the Honours Physics and Mathematics Program as a Canada Scholar and recipient of the CK Choi Presidential Award. In 2002, She moved to UC Berkeley as an NSERC fellow to pursue doctoral studies in optical and atomic physics. Under the guidance of Dr. Dan Stamper-Kurn, She pioneered imaging experiments of disorder-to-order transitions of atomic vapours held in optical traps. In 2009, she made a significant transition, from visualizing atoms in vacuum chambers, to visualizing biomolecules in liquids; a transition by a desire to get a little closer to life in her research. This transition to the Department of Chemistry and Chemical Biology at Harvard University was made possible with a Mary Fieser post-doctoral fellowship, with the mandate to explore this inspiration. At Harvard, she invented a single-molecule imaging technology called Convex Lens-induced Confinement (CLiC), which established her as a pioneer in single-molecule investigations with a range of applications. In 2012, she became an Assistant Professor at McGill University and founded her research group. Professor Leslie has developed CLiC into a platform technology and used it for new studies of nucleic acids, proteins, polymers, nanomaterials, biologics, cells, etc. To expand and commercialize her technology and key applications, she co-founded a start-up company ScopeSys, with a technical and business team based in Canada.
Group website