OSE Seminar by Dr. Quan Wang on Watching single biomolecules in action with optics, microfluidics and algorithms

Departmental News

Dr. Quan Wang

Posted: April 4, 2023

Speaker: Dr. Quan Wang of the National Institutes of Health

Date: Thursday, April 6, 2023

Time:  12:15 PM - 1:15 PM

Location: PAIS, Room 2540.

The ability to detect single biomolecules in aqueous solution provides a critical advance to understand biological function at the fundamental level. I describe my lab’s recent progress in building new and better single-molecule tools to monitor biochemical reactions in real time. First, I introduce ABEL-FRET, an immobilization-free platform for single-molecule Förster Resonance Energy Transfer (FRET) experiments. ABEL-FRET approaches shot-noise limited precision in FRET efficiency measurements and achieves ultrahigh resolution in heterogeneous mixtures. Moreover, ABEL-FRET simultaneously measures single-molecule diffusion coefficient and thus provides information on biomolecular interactions which contextualizes conformational dynamics. Second, I demonstrate sensing the charge state of single biomolecules, using principles similar to the Millikan’s oil drop experiment. This new modality enables direct monitoring of phosphorylation reactions, which is one of the most important post-translational modifications that modulate protein function. I illustrate with prototypical biochemical reactions involving DNA damage/repair enzymes and protein kinase.


Current Research:

We are currently developing new and improved methods that expand the capability of single-molecule fluorescence spectroscopy in solution. Building on a platform technology known as anti-Brownian Electrokinetic (ABEL) trapping to control a single biomolecule in solution, we simultaneously measure single-molecular size, charge (Nat. Methods 11, 555) and conformations (Nat. Methods 18, 816), together with their time-dependent dynamics in real time. These capabilities provide rich quantitative information on the oligomerization, phosphorylation and structural states and state transitions on a single biomolecule, and serve as a unique observation window into a wide range of biological processes.

Many scientific topics are being studied using our advanced single-molecule techniques, including nucleotide-dependent assembly/disassembly dynamics of multimeric enzymes, conformation change upon complex formation, biophysical impact of phosphorylation, dilute-phase molecular organization of biological liquid condensates. We gain biophysical insights by directly monitoring these processes at the single-molecule level, which has many advantages compared to traditional ensemble-level assays.

We are always looking for enthusiastic and motivated people. Learn about open positions in our lab at the postdoc, graduate student, and postbac levels.

Professional Experience:
Lewis-Sigler Experimental Fellow, Princeton University, 2016-2021
Ph.D., Stanford University, 2015
M.S., University of New Mexico, 2007

B.S., University of Science and Technology of China, 2005