Research
Physics of Biological Molecules
Many biological processes are facilitated by proteins. While the structure and action mechanism of proteins is extremely diverse, a handful of fundamental principles, including conformational flexibility, allosteric coupling, rare states, and diffusive transport, underlie a large portion of function. Understanding these fundamental principles remains an outstanding challenge in biophysics. My research interest is in resolving the underlying physics of protein function by leveraging emerging/state–of–the–art spectroscopy and microscopy techniques.
Motor Proteins
Our lab is interested in motor proteins operating far-from-equilibrium. Proteins like bacteriorhodopsin harness input energy to achieve directional transport. Understanding the molecular-basis for motor protein function requires sophisticated single-molecule experiments. Our group utilizes multidimensional single-molecule chemical exchange spectroscopy to study the thermodynamics and kinetics of the reaction cycle of motor proteins. In doing so, we hope to provide a general framework from which we can understand the function of proteins operating under nonequilibrium conditions.
Rare Fluctuations
The formation of the so-called activated complex (protein and substrate in correct position to react) is known to require significant conformational changes. For many chemical processes that modify the chemistry of nucleotides, the activated complex involves the flipping of bases out of the duplex. We are interested in characterizing these rare base flipping motions in DNA and resolving the role of rare conformations in protein binding. Novel single-molecule experiments have allowed for direct observation of the sequence of conformational motions involved in protein binding.
Microscopy Technique Development
The Abbe diffraction barrier stood for well over a century as the limit of spatial resolution for a far-field light microscope. In the past decade, however, several experimental techniques have demonstrated the ability to surpass this limit, opening up a new regime for optical imaging.
Our group works with Stimulated Emission Depletion microscopy to study nanoscopic structure and dynamics of soft matter. Part of our work is aimed at ushering super-resolution fluorescence microscopy into soft matter physics by exploiting the versatility of the technique to find new and productive ways of contrasting physical, chemical, and dynamic properties of soft materials (including polymer solutions, thin films, complex fluids, to name a few).
Spectroscopy Technique Development
We work on developing and adapting new approaches in single-molecule spectroscopy that allow for complex dynamics occurring on timescales of microseconds to seconds to be directly measured. We apply these techniques to biological macromolecules, and aim to answer open questions regarding the operating of directional proteins, formation of rare states, and role of spontaneous fluctuations in facilitating enzyme catalysis.