Office: ISA 4206
Lab: ISA 4045, 4049
Ph.D. Physics, 2009, Carnegie Mellon University
- Structure and function of membrane proteins
- Interactions between drug molecules and membrane proteins
- Structure and dynamics of fluid lipid membranes
- Protein-membrane interactions
- Drug-lipid composites
We are dedicated to initiating a top-notch structural and molecular biophysics laboratory located on the 4th floor of the Interdisciplinary Science building. Our main interests are centered on unveiling fundamental mechanisms dictating important biological processes. We use multitude approaches to achieve our goal. Experimentally, we use high power neutron and x-ray sources located at national facilities to interrogate structural and dynamical properties of biological composites. Theoretically, we collaborate closely with molecular dynamic simulators to decipher short time scale events that are responsible for meso- and macro-scale properties discerned from experimental measurements.
1. Ligand-gated ion channels complexed with allosteric drug molecules
Pentameric ligand-gated ion channels (pLGICs) comprise a superfamily of neuronal receptors that mediate fast synaptic transmission in the central and peripheral nervous system. They are the primary targets by many prevailing drug compounds aiming at detrimental neurological diseases. Although significant strides have been made towards our understanding of the operating principles behind the activation and modulation of pLGICs, structural elucidation remains a formidable challenge. A significant part of our research focuses on revealing atomic structures of pLGICs bound with allosteric drug molecules. In particular, we recently solved a high-resolution structure of the prokaryotic homolog, ELIC, bound with the endogenous neurotransmitter acetylcholine (Fig. 1), and GLIC bound with general anesthetic ketamine. The obtained complex structures offered valuable frameworks for deciphering structure-function relationships of pLGICs in action and are instrumental for designing new therapeutic drugs and anesthetics that modulate the function of pLGICs and alike.
2. Structures and dynamics of nanoscopic lipid membranes
Lipid membranes are large-scale self-assembled smart biomaterials that act as one of the building blocks of today's nanobiotechnology. As such, another part of our research is directed toward understanding the collective structural, mechanical and dynamical properties of lipid membranes in liquid disordered state. Using a combination of neutron and x-ray scattering, complemented with molecular dynamics simulations, we have successfully determined the effect of lipid head moiety on lipid membrane lateral packing. Moreover, we delineated why ether lipids may play a staring role in mediating cholesterol trafficking. This is primarily achieved by deciphering peculiar molecular interactions entailed by the unique backbone structure of ether lipids. Aside from static structures, neutron scattering also offers unique insights into dynamical properties of lipid membranes. Along this line, we are currently working on how minority constituents (e.g., drugs, peptides and proteins) may modulate overall and local material properties of the membrane matrix.
|14466||PHZ 4702||001||Appl of Phys to Bio/Med I|
Students must complere BOTH PHY 2053 and PHY 2054 or PHY 2048 and PHY 2049 with C (or better) grades before
|11489||PHY 7910||021||Directed Research|