Biophysics, Structural Biology
Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences
Dr. Tang is a principal investigator at the Center for Biomedical Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences in Wuhan, China.
Visualizing Protein Transient Structures
Chun Tang considers himself part biologist, part tool builder. As a postdoctoral fellow, he put a new twist on an old technique—nuclear magnetic resonance spectroscopy, or NMR—to study the behavior and function of proteins.
Classic NMR can detect the motion of individual atoms within a fixed protein, but his technique looks at proteins in solution, which allows researchers to see how their three-dimensional structures fluctuate and change shape. “My work is to develop new NMR methods to see how protein structures move in time and space,” says Tang, a researcher at Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences.
Tang grew up in the town of Suzhou, just outside Shanghai, a city known for its classical gardens and long tradition of scholarship. “Where I grew up, people with knowledge and who can think are valued. It’s a long tradition,” Tang says. He continued in the scholarly tradition by studying biology at Zhejiang University in Hangzhou, graduating in 1998 and setting his sights on graduate school.
He began learning about NMR and how it could provide vital information on the structure and interactions of proteins as a biochemistry graduate student at the University of Maryland, Baltimore County (UMBC). He worked with his advisor, HHMI investigator Michael Summers, to use NMR and other methods to visualize the structures of several proteins that are important in the life cycle of human immunodeficiency virus (HIV). Their studies led to identification of a class of inhibitors that target HIV maturation, a stage of the virus’s life cycle that leads to development of infectious viral particles.
In 2003, Tang started a postdoctoral fellowship at the National Institute of Diabetes, Digestive, and Kidney Diseases with biophysicist G. Marius Clore. There, he began developing the novel NMR methods that he continues to perfect today. Specifically, he pioneered a technique called paramagnetic relaxation enhancement (PRE), which allows researchers to see weak, short-lived protein interactions that are nevertheless important in protein function. In PRE, scientists attach a paramagnetic probe at a specific site in the protein under study and use NMR to image proteins. With the technique, researchers can capture a multitude of data on the shape-shifting contortions a protein goes through.
The theory for PRE has been around since the 1950s, Tang says, but “what we did is take the theory and implement it.” He applied the technique to studying the proteins in biological systems such as the HIV-1 protease and the bacterial phosphotransferase system, which transports sugar into cells. PRE proved to be a powerful tool for connecting protein dynamics with function.
After a two-year stint as an assistant professor at the University of Missouri–Columbia, Tang moved back to China in 2009, joining the Chinese Academy of Sciences’ Wuhan Institute of Physics and Mathematics. There, he relishes the opportunity to do “curiosity-driven stuff,” he says.
Tang continues to refine PRE so it can be used to give a more complete picture of proteins in time and space. “We’re looking at molecules, looking at the basic physical principles that govern those molecules to alter their conformation,” Tang says. “It’s the physical basis of life.”
With support from HHMI, Tang plans to move in a new direction with his research. A collaboration with Swiss researchers sparked his interest in ionotropic glutamate receptors—proteins that facilitate communication, memory, and learning in neuronal synapses. The binding domain of these receptors has a classic “Venus flytrap” structure consisting of two lobes that open as if on a hinge. When the receptor binds, the lobes open a pore that allows positively charged ions to flow into the neuron. This structure is common to many proteins, so learning about how this receptor works could provide insight into how other Venus flytrap-type receptors function.
Tang wants to use his PRE techniques to visualize how the receptor fluctuates between being open or closed, activated or at rest. Only very sensitive techniques will be able to reveal the receptor’s transient nature, he says. Malfunctioning ionotropic glutamate receptors have been implicated in many neurological disorders, including schizophrenia, Alzheimer’s disease, and Parkinson’s disease. Understanding how they work could lead to new treatments.
Though trained primarily as a biologist, Tang takes the scholarly ethos of his boyhood quite seriously, diving deep into physics to understand the theory behind NMR, for example. “It’s constant learning,” he says. “I always believed science should be curiosity driven. If you want to do very good science, you want to see what interests you and what is important.”