The structural biology laboratory can provide supports from protein expression, protein purification and protein structure determination. The laboratory has the capability to provide services in the following areas either for the instutute or outside organizations.
Major Research Programs
Protein expression and protein purification
The structural biology laboratory can provide pure, large quantity of proteins for biochemical studies, protein-drug binding assays or protein-based HTS assays. The laboratory is equipped with modern molecular biology equipment.
It can start from protein sequence analysis, secondary structure prediction, protein construct design and molecular cloning. Target genes are cloned into vectors for different expression systems. The final constructs will be transformed into different expression cell lines including coli, yeast and insect cells. Protein expression and purification will be performed in the large-scale level to obtain at least milligrams of protein. The laboratory has extensive experience in expression and purification of either soluble proteins or membrane proteins.
Protein structure determination
The laboratory can provide structural information of proteins with biological significance to help understand biological questions. The laboratory is able to determine the protein structure using X-ray crystallography.
The laboratory is equipped with a high-throughput screening system for protein crystallization. Thousands of conditions can be screened to obtain the initial hits for protein crystals. The initial crystallization conditions will be optimized to obtain high-quality crystals for X-ray diffraction. The initial data can be collected at the home-source X-ray facility, which is equipped with a Pilatus detector. The membership in SER-CAT allows us to assess beamlines at Argonne Proton Source (APS) for data collection on time. The protein structures can be determined using molecular replacement or ab initio methods, such as multi-wavelength anomalous dispersion (MAD). The laboratory is able to determine the structures of either soluble proteins or membrane proteins such as transporters.
Structure-based drug discovery
The major focus of the structural biology laboratory is to determine protein-compound structures to help compound development. The lead compounds identified through high-throughput screening or biological assays will be soaked into protein crystals or co-crystallized with target proteins.
The structure of a drug lead bound to a target protein can directly demonstrate drug-protein interactions and determine chemical modifications that can improve potency. The goal of the structure-based drug design is to accelerate the process of structure-activity relationship (SAR) to obtain more potent and stable compounds for target proteins. Currently, the laboratory mainly focuses on developing new drugs against infectious diseases such as HIV and cancers.
Meet Our Research Team
Mason Wu joined Southern Research in 2015 as a research chemist in the Chemistry Department, where he leads the Structural Biology Laboratory. His main interests are focused on structure-based drug discovery to develop drugs against cancer, infectious diseases and neurodegenerative diseases. Wu’s lab will provide support to every aspect of X-ray crystallography, including construct design, molecular cloning, protein expression and purification, crystallization, data collection, and structural determination. Wu received his bachelor’s and master’s degrees in biochemistry from Xiamen University in China. He subsequently obtained his doctorate degree in X-ray crystallography from National University of Singapore in 2006. Since 2007, Wu has been working in the Center for Membrane Biology at the University of Texas Health Science Center at Houston as a postdoctoral fellow and research assistant professor to study Ca2+ regulation and transport mechanisms of sodium calcium exchangers (NCXs) using structural biological approaches.