Genome stability and drug-resistance;

discovery of small non-coding RNA and their links with drug resistance in Mycobacterium tuberculosis;

Mechanisms of DNA replication and repair.

1997-2000: MSc, Shenyang Agricultural University, China. Purification of polyphenol oxidase from Nanguo pear.

2000-2003: PhD, Wuhan Institute of Virology, Chinese Academy of Sciences. Development of microarrays for detecting drug resistance in M. tuberculosis.

   

2008~ present Principle Investigator, Professor

Structural and Molecular Biology

Institute of Biophysics, Chinese Academy of Sciences

2004~ 2008 Principle Investigator, Associate Professor

Structural and Molecular Biology

Institute of Biophysics, Chinese Academy of Sciences

2003~2004 Postdoc Research Associate

Proteomics

                    Kinki University,Japan

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1. Zheng P, Xiong Q, Wu Y, Chen Y, Chen Z, Fleming J, Gao D, Bi L*, Ge F. Quantitative Proteomics Analysis Reveals Novel Insights into Mechanisms of Action of Long Noncoding RNA Hox Transcript Antisense Intergenic RNA (HOTAIR) in HeLa Cells. Mol Cell Proteomics, 2015, 14:1447-63. 

2. Yang M, Wang Y, Chen Y, Cheng Z, Gu J, Deng J, Bi L, Chen C, Mo R, Wang X, Ge F. Succinylome analysis reveals the involvement of lysine succinylation in metabolism in pathogenic Mycobacterium tuberculosis. Mol Cell Proteomics, 2015, 14:796-811.

3. Deng J, Bi L, Zhou L, Guo SJ, Fleming J, Jiang HW, Zhou Y, Gu J, Zhong Q, Wang ZX, Liu Z, Deng RP, Gao J, Chen T, Li W, Wang JF, Wang X, Li H, Ge F, Zhu G, Zhang HN, Gu J, Wu FL, Zhang Z, Wang D, Hang H, Li Y, Cheng L, He X, Tao SC, Zhang XE. Mycobacterium tuberculosis proteome microarray for global studies of protein function and immunogenicity. Cell Rep, 2014, 9:2317-29. 

4. Zhang H, Li D, Zhao L, Fleming J, Lin N, Wang T, Liu Z, Li C, Galwey N, Deng J, Zhou Y, Zhu Y, Gao Y, Wang T, Wang S, Huang Y, Wang M, Zhong Q, Zhou L, Chen T, Zhou J, Yang R, Zhu G, Hang H, Zhang J, Li F, Wan K, Wang J, Zhang XE & Bi L* Genome sequencing of 161 Mycobacterium tuberculosis isolates from China identifies genes and intergenic regions associated with drug resistance. Nature Genetics, 2013, 45: 1255-60.

5. Li W, Li D, Hu Y, Zhang XE, Bi L*, Wang D. Crystal structure of L, D-transpeptidase LdtMt2 in complex with meropenem reveals the mechanism of carbapenem against Mycobacterium tuberculosis. Cell Res. 2013, 23: 728-31.

6. Wang T, Sun H, Cheng F, Zhang XE, Bi L*, Jiang T. Recognition and processing of double-stranded DNA by ExoX, a distributive 3'-5' exonuclease. Nucleic Acids Research, 2013, 41: 7556-65.

7. Tao J, Han J, Wu H, Hu X, Deng J, Fleming J, Maxwell A, Bi L*, Mi K. Mycobacterium fluoroquinolone resistance protein B, a novel small GTPase, is involved in the regulation of DNA gyrase and drug resistance. Nucleic Acids Res. 2013 41: 2370-81.

8. Xiong Q, Zhong Q, Zhang J, Yang M, Li C, Zheng P, Bi L*, Ge F. Identification of Novel MiR-21 Target Proteins in Multiple Myeloma Cells by Quantitative Proteomics. J Proteome Res. 2012, 11: 2078-90.

9. Wu J, Zhang Z, Mitchenall LA, Maxwell A, Deng J, Zhang H, Zhou Y, Chen YY, Wang DC, Zhang XE, Bi L*. The dimer state of GyrB is an active form: implications for the initial complex assembly and processive strand passage. Nucleic Acid Res. 2011, 39: 8488-502.

10. Fu G, Wu J, Liu W, Zhu D, Hu Y, Deng J, Zhang XE, Bi L*, Wang DC. Crystal structure of DNA gyrase B' domain from Mycobacterium tuberculosis sheds lights on the mechanism for T-segment navigation. Nucleic Acids Res. 2009, 37: 5908-5916.

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1. M. tuberculosis genomics and transcriptomics

We have performed whole genome sequencing on 231 clinical isolates with different drug-resistance profiles collected from 12 provinces across China. Data analysis identified 72 new genes and 28 non-coding regions closely associated with drug resistance. We will use the new drug-resistant markers and drug targets identified in this work to establish new TB drug resistance testing methods and as a basis for drug development.

2. Development of a functional M. tuberculosis proteome microarray

We have constructed an M. tuberculosis protein expression library (containing 4262 proteins, providing 95% coverage of the MTB genome) which we are using to construct an M. tuberculosis functional proteome microarray that is based on purified proteins. This new experimental platform will greatly facilitate research on drug development and the development of new TB diagnostic reagents and vaccines.

3. Structure and function of M. tuberculosis drug targets

Our purpose in solving the structure of drug targets and investigating their functions is to provide a foundation for drug design and screening. We have completed a series of studies on the structure and function of quinolone targets in M. tuberculosis and have recently solved the crystal structure of L, D-transpeptidase (LdtMt2) in complex with meropenem. We are also designing and screening new drug precursor molecules.

4. TB Systems Biomedicine Resource and Information Database

This new resource will contain cell and serum samples from TB patients along with information on their treatment, clinical TB isolates and associated information, and extensive TB omics data. Our TB database will include a physical library of clinical resources in addition to the information resources commonly found in other TB databases and will have improved data display and analytical functions.

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已指导学生

钟天映  博士研究生  071011-生物物理学  

林世强  博士研究生  071011-生物物理学  

现指导学生

顾守进  硕士研究生  071010-生物化学与分子生物学  

张帅  硕士研究生  071010-生物化学与分子生物学  

焦健健  硕士研究生  085238-生物工程  

魏文静  博士研究生  071010-生物化学与分子生物学  

李文娟  博士研究生  071010-生物化学与分子生物学  

高云荣  博士研究生  071010-生物化学与分子生物学