Single-Molecule Studies of Function and Dynamics
My research program consists of two main themes: 1) Innovative technical developments
of novel single molecule tools, including combination of single molecule fluorescence and
biomechanical manipulations, and array-based high-throughput single molecule assays. 2)
Investigation of molecular mechanisms of biomolecules such as novel DNA and RNA
motifs, DNA motor proteins and membrane proteins using the techniques we develop. The
fundamental understanding achieved here will have further implications for medical and
bioengineering applications and may also help us design artificial machines that can approach
the efficiency, specificity and robustness of natural biomolecules.
Conformational Changes of Single RNA Molecules
RNA (ribose-nucleic acids) plays important cellular roles in information storage, transfer and processing
in addition to serving as a structural element for multi-protein complexes such as ribosome. It can form
a variety of unique 3D structures solely determined by its sequence, hence resembles proteins. We have
applied our single molecule approaches to study how an RNA molecule folds into 3D structure and
dynamically changes its shape spontaneously or in response to other bio-molecules or ions. Future
efforts will be focused on the conformational fluctuations of novel RNA structures with many degrees of
freedom to understand the role of metal ions in governing them.
Single Molecule Study of DNA Helicases
Nucleic acids unwinding is an essential step for many biomolecular processes. For
instance, DNA, containing genetic blue print for all living things, has a double helix
structure formed by two strands that needs to be ‘unwound’ or separated before
being copied. We successfully developed a unique single molecule approach that
can reveal the molecular mechanism of helicases that are not accessible by other
conventional methods. We will further develop our tools to investigate how
helicases consume free energy released by breaking chemical bonds in the ‘fuel’
molecule and couple it to their structural changes and propel themselves along DNA
molecule and unwind it. Innovative combination of fluorescence and manipulation
will be used to study how the linear and torsional tension on the DNA influence the
function of helicases.
Proteins on Biological Membranes
Many important biological processes occur on membranes. Supported lipid bilayer can serve as a great
model system to study protein-protein interactions and multi-protein complex organizations during
myriads of biological events including vesicle fusion and cell signaling. Single molecule fluorescence
techniques are well-suited for observing complex, multi-step processes of membrane proteins that are
very difficult to dissect in conventional ensemble studies. We are interested in studying the mechanism
of bilayer formation by vesicle fusion and developing new forms of bilayers that preserves the activity of
large trans-membrane proteins. Then, we will proceed to study how membrane proteins are recruited
and organized into a functional form upon external stimuli.
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