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NCKU transnational research team uncovers the structural basis for future development of potential asthma drugs

Tainan, Taiwan, October 17, 2013

National Cheng Kung University (NCKU) Department of Microbiology and Immunology Assistant Professor Dr. Shu-Ying Wang had her joint multidisciplinary research published in one of the world’s most prestigious academic journal, the Proceedings of the National Academy of Sciences of the United States of America (PNAS) recently.

The research article entitled “Structural insights into the Interaction of Interleukin 33 (IL-33) with Its Receptors” is in fact a joint effort with Beijing Tsinghua University Professors Dr. Xinquan Wang and Dr. Xi Liu, as well as Drs. Michal Hammel and John A. Tainer in Lawrence Berkeley National Laboratory, aiming to explore the molecular mechanism of IL-33 to provide structural basis for developing drugs to treat asthma and other innate immune disease.

The scientific reports in the past have shown that the outbreak and deterioration of hay fever, asthma, allergic rhinitis and other innate immune disease are related to IL-33, according to Dr. Wang.

She said, it was found that patients with these diseases have demonstrated higher content of IL-33 than normal people. IL-33 is the newest and the least understood member in the family of IL-1 cytokines. How IL-33 exerts its function to cause allergy and asthma has not yet been clarified.

“In our research, we combine the technologies of protein crystallography and small-angle X-ray scattering (SAXS) that enable us to visualize the high-resolution molecular interactions between IL-33 and its receptors, and discover unprecedented structural information, showing IL-33 receptor ST2 is flexible and exist in different conformation in solution” revealed Dr. Wang.

“This research is actually the outcome of hard work by many scholars for many years and is a multidisciplinary effort,” claimed Dr. Wang.

Dr. Wang added, “The project and collaboration were initiated by Prof. Xinquan Wang, who has a keen interest in studying structure-function relationship of IL-1 family of cytokines and has published the very first structure of ternary complex, composed of cytokine, receptor and co-receptor, in Nature Immunology in 2010. In order to truly understand how these molecules function in solution, Prof. Xinquan Wang called me to collaborate on this project by using the technique small-angle X-ray scattering (SAXS).”

Dr. Shu-Ying Wang has conducted the SAXS experiments for her research for years. She has been collecting the SAXS data, by collaborating the SAXS beamline scientist Dr. U-Ser Jeng, in National Synchrotron Radiation Research Center, Hsinchu, Taiwan.

During the progress of the IL-33 project, she realized more advanced data analysis and advanced setup for data collection were required. Therefore, she invited the world leading SAXS scientists and experts Drs. Michal Hammel and John A. Tainer in Lawrence Berkeley National Laboratory to join this project.

Dr. Wang says, rational drug design, which relies on the three-dimensional structure information, plays an important role in expediting the drug development process. By revealing the structural knowledge and understanding of molecular mechanism of IL-33, there will be higher possibility of developing new drugs in the future to effectively cure asthma and other innate immune disease.
Provider: 新聞中心
Date: 2013-10-17
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