Yawen Bai, Ph.D.
Dr. Bai pioneered native-state hydrogen exchange approach for revealing partially unfolded states of proteins. His recent studies of chromatin folding by methyl-based NMR approach have resulted structural insights into several important proteins in complex with the nucleosome.
Dr. Bai’s group is interested in understanding the basic principles that control the dynamic folding/unfolding processes of protein and chromatin using biophysical approaches. The failure of proteins to properly fold can impact their biological activity and/or stability, while the folding and compaction of DNA is critical for the regulation of gene expression and cell function. Defects in either of these processes can contribute to the development of many diseases, including cancer. Thus, an understanding of their folding mechanisms is critical for the advancement of cancer research, and for the discovery of potential treatment options.
Our long-term goal is to understand how DNA molecules in eukaryotic cells are folded to form chromatin, which is critical for the regulation of gene expression and cell function. The DNA molecules in eukaryotic cells are extremely long polymers that must be folded to more compact forms in order to fit within the small cell nucleus. A number of small positively charged proteins called histones help DNA fold. Core histones and DNA first form nucleosomes, the repeating structural unit of chromatin. Each nucleosome core particle contains eight histones (H2A-H2B-H3-H4)2 around which ~146 base pairs of DNA are wrapped. In addition, there is one linker histone for each nucleosome in higher eukaryotic cells. Linker histones are responsible for the formation of more compact higher-order structures of chromatin such as 30-nm fibers. The dynamic folding/unfolding processes of the nucleosome and chromatin are essential for cell function, and are regulated by a number of proteins, including histone chaperones, high mobility group proteins, and chromatin remodeling complexes. They play important roles in the epigenetic regulation of cell function. We use biophysical techniques, in particular the modern structural methods (NMR, X-ray crystallography and cryo-EM), to investigate: (i) interactions between histones and their chaperones, (ii) interactions between nucleosomes and nucleosome-binding proteins, (iii) and higher-order structures of chromatin.
For the last several years, we have revealed the structural basis for the recognition of histone variants (H2A.Z and CENP-A) by their chaperones (Chz1, Swr1-Z and Scm3). We have investigated the mechanisms of recognition of the canonical and CENP-A nucleosomes by HMGN and CENP-C molecules, providing the structural basis for the two-step epigenetic specification of chromosome centromeres. We have solved the structure of the nucleosome in complex with the linker histone (chromatosome). We have applied modern NMR methods to study nucleosomes in complex with linker histones and non-histone proteins.
If you are seeking a postdoctoral position, and prepared for challenging research, please inquire by sending your CV and a short statement of interest.
Selected Recent Publications
Structural Mechanisms of Nucleosome Recognition by Linker Histones.Mol Cell.. 59: 628-38, 2015. [ Journal Article ]
- Mol. Cell. 53: 498-505, 2014. [ Journal Article ]
- Science. 340: 1110-13, 2013. [ Journal Article ]
- Proc. Natl. Acad. Sci. U.S.A. 110: 19390-5, 2013. [ Journal Article ]
- Nature. 472: 234-7, 2011. [ Journal Article ]
Dr. Yawen Bai received his Ph.D. in biophysics from the University of Pennsylvania Medical School in 1994. He did his Ph.D. work in Walter Englander's lab, where he developed the native-state hydrogen exchange method to detect partially unfolded states of proteins. He completed his postdoctoral training in Peter Wright's lab at the Scripps Research Institute, where he studied protein folding using multi-dimensional NMR methods. He joined the Laboratory of Biochemistry of NCI as an independent investigator in 1997.
|Hanqiao Feng, Ph.D.||Staff Scientist|
|Bingquan Gao||Postdoctoral Fellow (CRTA)|
|Ruifang Guan Ph.D.||Postdoctoral Fellow (Visiting)|
|Jingjun Hong Ph.D.||Research Fellow|
|Bing-Rui Zhou Ph.D.||Research Fellow|