Bi-Cheng Wang, Ph.D.
The University of Georgia
Over the course of his career, B. C. Wang has been influential in transforming X-ray crystallography, a field considered important to drug development. He has shaped new technologies, promoted scientific collaboration and found new applications for tools and techniques – contributions that have made him a definitive leader in the field.
In 1997, Wang founded a consortium of 25 institutions that pooled their talents and resources to deepen exploration of X-ray crystallography. The consortium, called SER-CAT (for Southeast Regional Collaborative Access Team), works out of the Argonne National Laboratory’s Advanced Photo Source (APS). Located near Chicago, it is one of the most sophisticated X-ray facilities in the world, and through Wang’s efforts, its capabilities continue to improve.
X-ray crystallography is an experimental technique used by structural biologists. It allows researchers to look inside a single protein and analyze its structure and function, leading to advances in many fields, especially pharmaceutical design.
Researchers first “prepare” the protein by using chemical and physical processes to solidify it into a crystal. Then they expose it to a hyper-powerful X-ray source. Because the wavelengths in an X-ray beam are so tiny — about the size of a single atom — they bounce off individual atoms within the protein, scattering in a unique pattern as they emerge on the other side. Imagine light diffracting in a prism and becoming a rainbow — by reading this diffraction pattern, scientists can visualize the protein’s inner structure.
As technology has improved over the past 20 years, the possibilities for crystallography have expanded, too. Previously, crystallographers were forced to “label” the crystals they studied, inserting an internal marker, such as a heavier atom, to serve as a kind of navigation point. But Wang has been a proponent of another technique. Called "native single anomalous diffraction," it uses more sensitive instruments to look at unlabeled crystals. Along with providing new experimental techniques, Wang helped develop more advanced instrumentation and refined software that would render the labeling unnecessary and enable researchers to get much faster results.
One of Wang’s greatest achievements has been the construction of two synchrotron beamlines, the advanced, powerful X-ray beams needed for crystallography experiments. These were built at Argonne through the shared financial contributions of SER-CAT member institutions. Wang’s leadership in spearheading the project was invaluable, as the collaboration allowed institutions throughout Georgia and the Southeast to access technology far beyond the reach of a single campus, given that a single beamline costs about $7 million to construct.
During the beamline’s construction phase, Wang continued to innovate new techniques for collecting data. He participated in a NASA program of growing crystals inside the Mir space station and later helped review one of NASA’s biotechnology programs in space that involved performing experiments remotely. These experiments inspired an idea — if it was possible to manage an experiment between Earth and space, then connecting Georgia to Chicago should be easy.
So Wang and his colleagues developed a remote access system to give SER-CAT scientists a way to manage their experiments at Argonne’s Advanced Photo Source without traveling to Chicago. SER-CAT was the first group to have remote access at APS, which has saved valuable time and money.
Now, Wang is working on a pilot program to improve the beamlines further. They were originally optimized for a wavelength of 1 angstrom (about the size of an atom), but Wang has developed a plan to upgrade one of the beamlines so it may harvest wavelengths between 1 and 2.2 angstroms now, but extends to 3.5 angstroms in the future. This would enable researchers to adjust the beam to a particular wavelength to enhance the signals coming from selected atoms that are already part of the native protein as internal labels — another way of getting around artificial labeling.
It would also allow researchers to use a stretch of continued wavelengths to produce wavelength-dependent images of the structure – an idea equivalent to a camera that can record the colors (different wavelengths of the light) of every part of an object versus only black-and-white (ignoring the color) pictures of the object. Wang hopes the pilot program will demonstrate the necessary results for supporting the APS’ consideration of building a new type of beamline during its upcoming upgrade period to assist future researchers in fully utilizing tunable synchrotron X-rays to effectively explore additional and/or new applications of crystallography in Chemistry, Biology, Physics and Engineering.
Together, SER-CAT has produced data on more than 2,500 protein structures. The consortium also advanced the research of a scientist who was runner-up for Breakthrough of Year 2013 by the international journal Science.
Wang’s research interests include:
- Protein crystallography as a technique for studying the structure and function of biological macromolecules.
- Development of synchrotron X-ray beamlines, and other advanced instrumentation for diffraction studies, including remote access systems, robotic sample mounting technologies and new applications of tunable synchrotron X-rays.
- Direct determination of unlabeled native protein structures by sulfur phasing.
- Investigation of human membrane protein receptors including the dopamine receptor, the serotonin receptor, the NMDA receptor, the olfactory receptor, and single-chain antigen-binding proteins.
Wang also headed the Southeast Collaboratory for Structural Genomics (SECSG), one of the first seven NIH pilot centers for structural genomics. SECSG made significant strides in developing more efficient, more affordable techniques for X-ray crystallography.
The strong commitment from the University of Georgia and the Georgia Research Alliance to building world-class facilities for structural biology was the major reason for moving to Georgia. The continued support from the Georgia Research Alliance toward research activities in the state and research visions of its Eminent Scholars has made Georgia an excellent environment for growth and productivity in interdisciplinary, cutting edge research and provided a confirmation that it was a right decision for me to come to Georgia fifteen years ago.
1 patent issued