Research Interests

We are interested in membrane biophysics and focus on 3 projects:

(1)  Biomolecular Interactions at Interfaces
We apply surface-sensitive second-order vibrational sum frequency generation (SFG) spectroscopy to investigate the folding of intrinsically disordered proteins (IDOPs) at membrane surfaces.IDOPs are abundant in human body and their aggregation into highly ordered fibrils is associated with many diseases such as Parkinson’s disease, Alzhiemer’s disease, and type II diabetes. We will use SFG to probe the vibrational structures of the proteins as they fold into secondary and tertiary structures at membrane surfaces. The results will provide insight into pathology of the diseases at the molecular level and guidance for incorporating IDOPs into the development of novel biomaterials. (Ref: Appl. Spectrosc. 2009, 63, 528)

(2) Signal Transduction across Biomembranes.
We focus on 7-alpha-helical transmembrane G protein-coupled receptors (GPCRs) that belong to the largest gene family in the human genome and represent important drug targets.  We use bioreactor to culture mammalian cells to express GPCRs in milligram scale and developing method to purify GPCRs using nanoscale lipid bilayer disc particles (NanoDiscs). We apply unnatural amino acid mutagenesis to site-specifically incorporate spectroscopic probes into GPCRs. Because purification of GPCRs in the quality and quantity that allows quantitative biophysical studies is one of the biggest challenges in the field, this approach could potentially provide a breakthrough to apply biophysical spectroscopy to obtain highly selective spectroscopic readout to investigate conformational changes of GPCRs. (Ref: J. Biol. Chem. 2008, 283, 1525)

(3) Molecular Mechanism of Vision
GPCR rhodopsin is an extremely sensitive biological light detector. Rhodopsin contains a chromophore, 11-cis retinal, which undergoes photoisomerization to trigger conformational changes in 7-helical transmembrane opsin protein for initiating a visual signal. In the dark, 11-cis retinal can very occasionally overcome the energy barrier to undergo thermal isomerization. Thermal isomerization produces the same physiological response as photoisomerization, and hence generates dark noise. The rate of thermal isomerization in rod photoreceptor cells is extremely low, once in every 420 years! The origin of low rate of thermal isomerization remains unspecified and is the key to understand the molecular mechanism of dim-light vision. Applying site-directed mutagenesis and performing kinetic analysis of the thermal decay process of rhodopsin, we aim to understand the fundamental of the low dark noise level of rhodopsin. (Ref: J. Am. Chem. Soc. 2009, 131, 8750)