Sabrina Leslie's research program creates and applies microscopy instrumentation to enable scientific discoveries in biophysics and materials science research, ranging from fundamental, to applied. Our mission statement is new tools yield new discoveries, and our pleasure is in creating both. One thrust of our research program strives to create a mechanistic understanding of conformational DNA dynamics, key to tackling a wide range of open biological questions. How do protein-DNA searches and binding kinetics occur sufficiently quickly to mediate life-preserving processes such as DNA repair, transcription, and translation? We are fascinated by how DNA molecules behave under nanoscale confinement, a problem which is highly relevant to understanding DNA dynamics and protein-DNA interactions in the nucleus of a cell.
To provide microscopic insights into longstanding biological questions, we invent, engineer, and machine single-molecule microscopy tools that are newly capable of simultaneously measuring: weak protein-DNA and DNA-DNA interactions; extended search trajectories of individual molecules over several seconds; millisecond-timescale interaction kinetics; and topologically complex or strained DNA substrates. In a complementary applied program, we harness our tunable, nanoscale imaging chambers and custom device topologies to develop new kinds of biomedical diagnostics. We squeeze, trap and interrogate molecules in different ways, allowing for direct visualization of cellular content with single-molecule resolution.
A second thrust of our research program uses similar instrumentation to create optical diagnostics of tunable materials properties, with a wide range of applications and in direct connection with industry. Our collaborative team of physicists, engineers, computer scientists, molecular biologists, and cellular biologists is deliberately mixed and evolving. Combining knowledge, talent and experience across disciplines is potent for scientific discovery.