Department of Physics, Engineering Physics & Astronomy

Department of Physics, Engineering Physics & Astronomy
Department of Physics, Engineering Physics & Astronomy

Departmental Colloquium - Squeezing New Information out of DNA

Sabrina Leslie,
University of McGill

January 29th, 2016
1:30 p.m. in Theatre A

Abstract:

How macromolecules behave in nanoconfined spaces, such as what conformations DNA polymers adopt and how they interact with other DNA and protein molecules, is of immense fundamental as well as applied interest, warranting new biophysical explorations. In the context of cellular biophysics, compact coiled DNA molecules are squeezed within a nucleus, presenting open questions regarding their properties and interactions. In the context of genomics, nanofluidic tools often work by squeezing polymers into long nano pipes, with the hope of directly unraveling the sequence of our genetic code, using small numbers of intact DNA segments. One holy grail of modern biotechnology is reading, assembling and understanding single-cell genomes with minimal fragmentation. However, handling and visualizing long and delicate strands of genomic DNA represent key technological challenges, typically breaking DNA into tiny pieces.

In this talk, we harness capabilities of a novel single-molecule manipulation and microscopy platform we have developed called “Convex Lens-induced Confinement (CLiC)” for two explorations in biophysics. First, we demonstrate a new and gentle approach to directly manipulate and visualize long, purified strands of DNA for genomic analysis which is high-throughput, compatible with in-situ reagent exchange and controlled chemistry in nanofluidic environments, and relies on tiny entropic forces (Berard et al, PNAS 2014). We precisely explore the polymer physics underlying the DNA polymers’ behaviour as a function of applied confinement, and compare results to theory, which we consequently extend. Second, using more complex supercoiled DNA systems, closer to physiological conditions, we study how their conformational fluctuations mediate invasion into spontaneous unwinding sites by small oligonucleotides. Motivated by open questions on transcriptional initiation and dynamics, and beginning with model systems, our single-molecule reaction and trajectory visualizations can provide new mechanistic insights. The overarching vision of this talk is that by “getting into that room at the bottom” of nanobiophysics by innovative technologies, we open doors to complementary biophysical discovery and biomedical diagnostics which can act hand in hand.

 
Biosketch:

Dr. Sabrina Rose Leslie is an Assistant Professor of Physics at McGill University where she has lead her single-molecule biophysics laboratory since January 2012. Prior to her Faculty appointment, she was a Mary Fieser Post-doctoral Research Fellow in the Department of Chemistry and Chemical Biology at Harvard University from 2009 to 2011, where she pioneered new single-molecule imaging techniques. Leslie earned her Ph.D. in optical and atomic physics in the Department of Physics at Berkeley during 2002 to 2008, with a common theme of nanoscale cinematography, but with applications to visualizing cold molecular dynamics in atomic vapours. In transitioning to study the wet and squishy biophysical world, she leverages expertise in optics, instrumentation, microscopy and physical theory. Her group innovates new ways to manipulate and visualize biomolecules on the nanometer scale, leading to new biomedical diagnostics as well as pursuing fundamental biophysical discoveries.