About Our Research

We are broadly interested in the fundamental link between the physical properties of biological molecules, nanoscale dynamics and biological functions. We develop novel and improved single-molecule spectroscopic tools to directly observe biological processes at the nanoscale in solution. As is often the case in scientific research, new methods open the door to exciting new observations. To gain biological insights, we use (or develop) proper statistical analysis and build quantitative models. Current projects in the lab include:

  • ABEL-FRET spectroscopy: building on our recent work (Nat. Methods 18, 816) that demonstrated tether-free single-molecule FRET with hydrodynamic profiling, we are developing the next generation instrument that offers the highest possible resolution in both space (i.e. smFRET efficiency) and time. We are also applying the technology to study the interplay between binding and conformational change of single RNA molecules.
  • Nucleotide dependent assembly dynamics of a multimeric enzyme: many proteins require the formation of a certain oligomerization state to properly function. Revealing the interplay between dynamic assembly/disassembly, nucleotide binding, subunit communication/cooperativity holds the key to understanding how the multimeric enzyme works. Using our unique single-molecule tools, we focus on tobacco Rubisco Activase, a chaperone for carbon fixation, as a model system to explore these questions.
  • Probing single-molecule phosphorylation: we are developing methods to monitor single-molecule phosphorylation and dephosphorylation events in real time. Together with ABEL-FRET, we aim to measure how the addition of a phosphate group alters the conformation of a single protein substrate, thus shedding light on the biophysical basis of phosphorylation activation.
  • Single molecules in and out of biological condensates: liquid-liquid phase separation has recently emerged as an important paradigm for cellular organization. We are designing single-molecule experiments to probe the molecular conformation, organization and biological activities in both the dense and dilute phases, hoping to better understand this phenomenum at the molecular level.

Research Images