Chemical Society Seminar: Sabrina Leslie - Deconstructing biology with simple single-molecule imaging: Controlling conformation, confinement, and concentration

Abstract:

Molecular biology is messy and complex. The future of life sciences research, drug development, and many other fields depends on our ability to unravel the complex, molecular phenomena that underlie cellular function. Using currently available technologies, it is still challenging and costly to conduct single-molecule measurements that can potentially reveal the true complexity of life at the molecular scale. Convex Lens-induced Confinement (CLiC) microscopy is a simple, general method of imaging molecular interactions one molecule at a time. By mechanically confining molecules to the field of view, CLiC eliminates the complexity and potential biases inherent in methods such as optical tweezers and TIRF. In this talk I discuss how we employ CLiC to investigate how DNA supercoiling regulates the dynamic unwinding of specific target sites, and the activity of molecules binding to these sites – important biophysical questions for medicine and antisense oligonucleotide drug development (Scott et. al., Nucleic Acids Research 2018). I will also introduce new and emerging areas of exploration with CLiC including protein droplets, nanoparticle dynamics, CRISPR-Cas9 search processes, and therapeutics applications.

Bio:

Dr. Sabrina Leslie is an Associate Professor of Physics and Quantitative Life Sciences at McGill University. She founded her single-molecule imaging laboratory in 2012, where she has pioneered new techniques to shed light into the elusive and complex interactions and dynamics of macromolecules. Her academic training began in 1998 as an undergraduate at UBC, where she graduated from the Combined 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 physics. In 2009, she transitioned from visualizing hard to soft materials, focusing on biomolecules in liquids. 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 her passion for imaging in a health sciences context. 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. To expand and commercialize her technology and basic research ideas, she has recently co-founded a start-up company, ScopeSys, which has business offices in Montreal and Vancouver.