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Finding Genius Podcast

Nov 29, 2018

Dr. Sabrina Leslie, Associate Professor of Physics and Quantitative Life Sciences at McGill University, leads listeners on an interesting journey into the complex and important world of molecule imaging and research.

As an experienced researcher and respected university leader at McGill, Dr. Leslie founded her single-molecule imaging laboratory in 2012. The lab was instrumental in the development of novel techniques to discover and explore complex interactions and dynamics of macromolecules. Dr. Leslie has pursued doctoral studies in optical physics, has completed extensive research on biomolecules in liquids, and explored her passion for imaging in a health sciences context. She is a recipient of a Mary Fieser Postdoctoral Fellowship, and her work at Harvard led to the invention of a single-molecule imaging technology known as Convex Lens-induced Confinement (CLiC). And it was this groundbreaking work in the field that thrust her onto the international stage as a noted pioneer in single-molecule investigations with a broad range of applications. Dr. Leslie earned her Ph.D. in Optical and Atomic Physics at the University of California at Berkeley

Dr. Leslie discusses her lab’s intensive work deconstructing molecular interactions to answer questions in biology and develop new drugs for medical and therapeutic applications. She talks about the importance of time scales, speed of camera, and resolution, in their work as they seek to visualize the interactions in real time. By using cameras they are able to watch molecules for a long time and deconstruct the methods of operation.

Collaborating with biochemists and cancer scientists, as well as applied mathematicians, the Leslie Lab’s single-molecule investigations of protein and DNA interactions, have provided significant new information about gene regulation mechanisms. Specifically, Dr. Leslie’s work has also been focused on exploring a wide range of interactions and dynamics of proteins and DNA, as well as other macromolecules, and with regard to molecular shape and environment. 

The macromolecule researcher details her lab’s groundbreaking work with the imaging technology known as Convex Lens-induced Confinement (CLiC). As she explains, the process works by essentially squeezing the tiny molecules into little traps so that the essence of the molecule is completely held in focus, viewable from all angles. And by utilizing fluorescent labels they are able to closely track them for observation. 

She details some of their current research regarding DNA binding with a focus on applications and therapeutics, etc. As they continued their experimentation they began introducing other molecules and polymers, to fill up space and then observe how DNA probes find their target sites. As she states, they have a particular interest in the nexus between the physics and the biology, where structural elements can have an impact on the biochemical reactions. Further, she talks about some surprising discoveries regarding proteins and droplet formation simulation. 

In concert with biochemists in Montreal, Dr. Leslie’s team is instigating CLiC studies of non-membranous organelles (NMOs). Liquid droplets form when proteins and nucleic acids phase-separate from cellular material, similar to how oil separates from water. Importantly, there is significant evidence suggesting that misregulation of MMOs is associated with select diseases such as Alzheimer’s.

Lastly, Dr. Leslie expounds upon some of the areas of research they are most excited to dig into, such as gene editing, and she gives an overview of their collaborations with pharmaceutical companies on oligonucleotide therapeutics. (Oligonucleotide therapeutics is an inventive class of biopharmaceutical products composed of short strings of synthetic nucleotides that resemble the actual building blocks for DNA.)