Michelle D. Wang
Professor of Physics
Howard Hughes Medical Institute Investigator
B.S., 1985, Physics, Nanjing University. Ph.D. student, 1985-86, Institute of Physics, Chinese Academy of Sciences. M.S, 1988, Physics, University of Southern Mississippi. Ph.D., 1993. Biophysics, University of Michigan at Ann Arbor. Postdoctoral Fellow, Biophysics, Princeton University, 1994-97. Assistant Professor, Physics, Cornell University, 1998-2004. Associate Professor, Physics, Cornell University, 2004-2009. Professor, Physics, Cornell University, 2009-present. Outstanding Student Award, Nanjing University, 1985. University of Michigan Biophysics Fellowship, 1988-89. National Cancer Institute Fellowship, 1994. Damon Runyon-Walter Winchell Foundation Postdoctoral Fellowship, 1995-97. Damon Runyon Scholar Award, 1999-00. Dale F. and Betty Ann Frey Scholar of the Damon Runyon-Walter Winchell Foundation, 1999. Alfred P. Sloan Research Fellow, 1999-01. Beckman Young Investigator Award, 1999-02. Keck Foundation Distinguished Young Scholar in Medical Research Award, 2000-07. Provost's Award for Distinguished Scholarship, 2008. Fellow, American Physical Society, elected 2009. Howard Hughes Medical Institute Investigator, 2008-present.
Single molecule mechanical manipulations of biological molecules; high-resolution optical trapping and detection; single molecule fluorescence imaging and detection; nanophotonics and lab-on-a-chip; molecular motor mechanisms; biopolymer kinetics and dynamics; protein-DNA interactions during transcription and replication; modeling of diffusion, kinetics, and dynamics of biomolecules.
We are primarily a single molecule biophysics lab based in the Department of Physics at Cornell University. Our current research focuses on the motion, dynamics, mechanisms, and regulation of molecular motors that translocate along DNA during the replication and transcription of DNA. To work with biological motors at the single molecule level, we develop and utilize state-of-the-art (and often one-of-a-kind) instruments and novel techniques. Here we’ll highlight a few novel experimental approaches that we have recently developed.
Angular Optical Trapping
Our lab pioneered an angular optical trapping technique for simultaneous torque and force generation and detection (La Porta et al., Physical Review Letters, 2004; Deufel et al., Nature Methods, 2007). When a birefringent particle is trapped in a polarized laser beam, rotation of the laser polarization induces rotation of the particle, while torque exerted on the particle is detected as a change in the polarization of the trapping beam. This technique allows the control and detection of the torque of a biological molecule attached to the particle and has opened new dimensions for applications of optical trapping techniques. We have used this technique to determine torque during DNA supercoiling (Forth et al., Physical Review Letters, 2008; Sheinin et al., Physical Review Letters, 2011) and during a Holliday junction migration (Forth et al., Biophysical Journal, 2011). More recently, we have measured the torque generated by the RNA polymerase motor during transcription (Ma et al., Science, 2013).
Protein-DNA interactions dictate gene expression and replication. Although several techniques are able to detect the location of an interaction, few are able to measure its strength, a critical determinant of DNA accessibility. Our lab developed the powerful and versatile DNA unzipping method to measure protein-DNA interactions (Koch et al., Biophysical Journal, 2002; Koch and Wang, Physical Review Letters, 2003; Shundrovsky et al., Nature Structural and Molecular Biology, 2006; Hall et al., Nature Structural and Molecular Biology, 2009). Using an optical trap, we mechanically separate a double-stranded DNA (dsDNA) with bound proteins into two single strands. As the unzipping fork reaches a bound protein, the unzipping force increases dramatically, and then reduces suddenly as the interaction is disrupted. Typically, multiple interactions are detected for a given protein, and the unzipping method maps the locations of these interactions to near single-base-pair precision, while also providing a quantitative measure of their strengths. A variation of this approach also has also allowed us to gain mechanistic insights into a helicase motor that carries out DNA strand separation activities (Johnson et al., Cell, 2007; Sun et al., Nature, 2011).
Optical trapping techniques have proven to be powerful tools. In the past three decades, they have transformed many areas of biochemistry and molecular biology. Yet these techniques are typically restricted to a specialized group of individuals who spend many years constructing a single instrument, followed by repeated measurements, one molecule at a time. In order to make these techniques accessible to a broader scientific community, a new generation of optical trapping instruments is essential. A ‘plug-and-play’ instrument, capable of manipulation with both high resolution and high throughput, would potentially revolutionize the single molecule field. As the first step towards this goal, we demonstrate dynamic optical trapping control of nanoparticles by an optofluidic waveguide-based resonator (Soltani et al., Optics Express, 2012). We introduce a new platform in which the photonic device is controlled using electro-optical phase tuning. This novel electro-optofluidic platform allows the realization of high throughput optofluidic devices with switching, tuning, and reconfiguration capability.
Robert Forties, Jun Lin, Jie Ma, Mohammad Soltani, Bo Sun, and Yi Yang
Lucy Brennan, James Inman, Jessie Killian, Ming Li, and Summer Saraf
Dr. Shanna Fellman