Our research focuses on developing novel single-molecule methods to characterize and understand the properties of biological systems and nanoscale materials. As compared to traditional ensemble measurements, the single molecule approach removes ensemble averaging, so that distributions and fluctuations of molecular properties can be characterized and transient intermediates identified. Our research program provides students with scientific training spanning from sophisticated spectroscopic techniques, rigorous data analyses, high level theoretical calculations to protein engineering using modern molecular biology techniques, as well as nanotechnology and nano-materials.
Currently our research has two main directions: (1) single-molecule bioinorganic chemistry, and (2) single-nanoparticle catalysis.
1) Single-molecule bioinorganic chemistry.
This research direction in our group resides at the interface of bioinorganic chemistry and single molecule biophysics. (See our publication #19 for a review on single-molecule bioinorganic studies.) We aim to use single-molecule methods to address compelling scientific questions concerning metalloproteins/enzymes. Specifically, we are working on three projects in this direction:
Protein-protein interactions for
metallochaperone mediated metal
transfer.
Metallochaperones protect and deliver metal ions to
their target metalloproteins via specific protein-protein interactions, and
play essential roles in intracellular metal ion regulation and metabolism.
We are studying the dynamics of the protein-protein interactions and the
associated metal transfer processes involving metallochaperones using single
molecule fluorescence techniques. We have used nanovesicle trapping to
enable single-molecule FRET studies of weak interactions between the copper
chaperone and the Wilson Disease protein (Figure 1, and
publication #21), and
quantified their interaction dynamics for understanding their functions.
Figure 1. Nanovesicle trapping combined with single-molecule FRET for studying transient and weak protein interactions.
Protein-DNA interactions for metalloregulator
mediated transcriptional regulation.
Metalloregulators respond to metal ion concentrations
via conformational changes that lead to their different interactions with
their target DNA sequences and thus transcriptional regulation in gene
expression. We are studying the conformational dynamics of metalloregulators
and DNA, and their interaction dynamics involved in these regulation
processes. We have developed a novel single-molecule method using engineered
DNA Holliday junctions as single-molecule reporters to study
metalloregulator-DNA interactions (Figure 2, and
publication
#18). By encoding targeting sequences in a DNA Holliday junction,
protein actions on the DNA are converted to the changes on the structural
dynamics of the engineered Holliday junction, which can be followed easily
at the single-molecule level.
Figure 2. Engineered DNA Holliday junctions as generalizable single-molecule reporters for protein-DNA interactions.
Single molecule bioinorganic enzymology.
We are working on following individual enzymatic cycles of metalloenzymes one
molecule at a time. By following catalytic reactions one event at a time, we
hope to gain fundamental understanding of enzyme catalysis and related
reaction mechanisms.
(2) Single-nanoparticle catalysis.
This research direction in our group is to use single-molecule methods to study the catalytic properties of nanoparticles at the single-particle level. Nanoparticles are important catalysts, but have intrinsically heterogeneous activities due to their structural dispersions and variable distribution surface active sites. Studying the catalysis of nanoparticles at the single-nanoparticle level can reveal many unprecedented details about their activity-structure correlations. Stay tuned for our forthcoming publications!