Imaging Molecular Machines at the Single-Molecule Scale
Research efforts in the Blanchard lab are bridging the intellectual gap between knowledge of static molecular architecture and the fundamentally dynamic nature of biological processes. A layman's statement of the question we aim to address is: How do enzymes move when they work?
To answer this question the lab is actively engaged in the development and implementation of single-molecule imaging techniques. Investigations at the single-molecule scale shed light on processes masked by ensemble averaging in bulk investigations and provide the first direct means of measuring stochastic, time-dependent fluctuations in enzyme structure and/or composition. Our investigations probe how these processes relate to their essential functions. We are particularly interested in developing broadly applicable methods for measuring enzyme function from an intuitive perspective of motion using single-molecule Fluorescence Resonance Energy Transfer (smFRET).
Efforts in the lab are presently focused on the function of macromolecular machines, highly organized amalgams of numerous individual gene products. These complex enzymes are central to many biological processes and are proven drug targets. They also typically defy reductionist approaches to structural and functional interrogations. Using smFRET, combined with computational modeling and molecular dynamics simulations, ongoing investigations focus on the generation of experimentally-validated movies of working molecular machines and a deeper understanding of basic enzyme function and regulation.
Dr. Blanchard is the Co-Director of the Tri-Institutional Chemical Biology Program.