Education

2000 - 2003: Graduate student (Ph. D. degree)

Wuhan Institute of Virology, Chinese Academy of Sciences

Development of microarrays for detecting drug resistance inM. tuberculosis.

Supervisor: Professor Xian-En Zhang

1997 - 2000: Graduate student (M.Sc. degree)

Shenyang Agricultural University, College of Food Science

Purification of polyphenol oxidase from Nanguo pear.

Supervisor: Professor Yansong Ma

1993 - 1997: Undergraduate student (B.Sc. degree)

Food Science

Henan University of Science and Technology

Research Experience

2008 - present: Principle Investigator, Professor

Tuberculosis Systems Biology and Translational Medicine

Institute of Biophysics, Chinese Academy of Sciences

M. tuberculosisdrug resistance and pathogenesis; Translational medicine

2011(03 - 07): Visiting Professor in the laboratory of Prof. John Chan,

Department of Microbiology and Immunology, Einstein Institute of Medicine, New York.

M. tuberculosisinfection and host immunology.

2004 - 2008: Principle Investigator, Associate Professor

Structural and Molecular Biology

Institute of Biophysics, Chinese Academy of Sciences

2003 - 2004: Postdoctoral Research Associate

Proteomics: Quantitative proteomics of transgenic mammal single cells.

Kinki University, Japan

2020 Chinese Academy of Sciences Outstanding Party Member

2019 Chinese Academy of Sciences (Beijing): Honored Woman Worker

2018 Winner of the first China Anti-Tuberculosis Association "Most Exemplary Anti-TB Champion" Award

2017 First prize in the National Innovation Competition

2016 China Anti-Tuberculosis Association Excellence in Science and Technology Award

2015 Guangdong Province Zhujiang Talent Innovation Team, Head

2013 Awarded the title of Foshan Leader in Entrepreneurship

2019.09 - present Standing Committee Member of the TB Prevention and Treatment

Branch of the China Association for the International Promotion of Medical and Health Care

2017.05 - 2020.05 Chairman of the TB Basic Research Committee, TB Branch Chinese Medical Association

2016.07 - present Chairman of the TB Translational Medicine Branch of the Chinese Anti-Tuberculosis Association

2016.07 - present Journal of Biological Chemistry Editorial Board Member

2015.12 - present Member of the Standing Committee of the TB Basic Research Branch of the Chinese Anti-Tuberculosis Association

2011.10 - 2016.10 Member of the Analytical Microbiology Committee of the Chinese Society of Microbiology

2011.04 - 2015.04 Deputy Chairman of the Basic Bacterial Immunology Committee of Chinese Anti-Tuberculosis Association

2009.07 - 2013.06 Deputy Secretary-General of the Chinese Biophysical Society

My research focuses on problems encountered in the diagnosis and treatment of TB, including the poor detection rate of TB, the rise of drug resistance, the poor protection afforded by the current BCG vaccine, and the lack of drugs for treating latent TB infections. My group collaborates widely and our network spans different disciplines and institutes, both nationally and internationally. We have developed new research methods and techniques based on the concepts of systems biomedicine, and have identified new biomarkers, immunogens and drug targets. (>80 publications and >10 patents)

1.Mycobacterium tuberculosisgenomics and transcriptomics

We have used whole genome sequencing of clinical isolates with different drug-resistance profiles from across China to identify new genes and non-coding regions closely associated with drug resistance. These new drug-resistant markers and drug targets are being used to establish new TB drug resistance testing methods and develop new drugs.

2. FunctionalM. tuberculosisproteome microarrays

We constructed anM. tuberculosisprotein expression library (providing 95% coverage of the MTB genome) and anM. tuberculosisfunctional proteome microarray (and sub-arrays). These new experimental platforms are facilitating research on drug development and the development of new TB diagnostic reagents and vaccines.

3. Structure and function ofM. tuberculosisdrug targets

We have solved the structure of drug targets to facilitate functional investigations and provide a foundation for drug design and screening. We have completed studies on the structure and function of quinolone targets inM. tuberculosisand 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 Resources

Our database contains cell and serum samples from TB patients along with information on their treatment, clinical TB isolates and associated information, and extensive TB omics data. We have a physical library of clinical resources and information resources similar to those found in other TB databases.

1. Wang Y, Li Z, Wu S, Fleming J, Li C, Zhu G, Chen B, Ren B, Wang X, Du B, Li P, Hu P, Yang J, Liu Y, Zhou C, Zhang XE,Bi L, Zhang H, Yang J, Zhang Z. Systematic Evaluation of Mycobacterium tuberculosis Proteins for Antigenic Properties Identifies Rv1485 and Rv1705c as Potential Protective Subunit Vaccine Candidates.Infect Immun. 2021 Feb 16;89(3):e00585-20.

2. Zhang S, Li T, Huo Y, Yang J, Fleming J, Shi M, Wang Y, Wei W, Gu S,Bi L*, Jiang T, Zhang H. Mycobacterium tuberculosis CRISPR/Cas system Csm1 holds clues to the evolutionary relationship between DNA polymerase and cyclase activity.Int J Biol Macromol. 2021 Feb 15;170:140-149.

3. Hu P, Zhang H, Fleming J, Zhu G, Zhang S, Wang Y, Liu F, Yi S, Chen Z, Chen Z, Liu B, Gong D, Wan L, Wang X, Tan Y, Bai L,Bi L*. Retrospective Analysis of False-Positive and Disputed Rifampin Resistance Xpert MTB/RIF Assay Results in Clinical Samples from a Referral Hospital in Hunan, China.J Clin Microbiol. 2019 Apr;57(4):e01707-18.

4. Wei W, Zhang S, Fleming J, Chen Y, Li Z, Fan S, Liu Y, Wang W, Wang T, Liu Y, Ren B, Wang M, Jiao J, Chen Y, Zhou Y, Zhou Y, Gu S, Zhang X, Wan L, Chen T, Zhou L, Chen Y, Zhang XE, Li C, Zhang H,Bi L*. Mycobacterium tuberculosis type III-A CRISPR/Cas system crRNA and its maturation have atypical features.FASEB J. 2019 Jan;33(1):1496-1509.

5. Gao YR, Li DF, Fleming J, Zhou YF, Liu Y, Deng JY, Zhou L, Zhou J, Zhu GF, Zhang XE, Wang DC,Bi LJ*. Structural analysis of the regulatory mechanism of MarR protein Rv2887 in M. tuberculosis.Sci Rep. 2017 Jul 25;7(1):6471.

6. Wang M, Fleming J, Li Z, Li C, Zhang H, Xue Y, Chen M, Zhang Z, Zhang XE,Bi L*. An automated approach for global identification of sRNA-encoding regions in RNA-Seq data from Mycobacterium tuberculosis.Acta Biochim Biophys Sin (Shanghai). 2016 Jun;48(6):544-53.

7. Gu S, Li W, Zhang H, Fleming J, Yang W, Wang S, Wei W, Zhou J, Zhu G, Deng J, Hou J, Zhou Y, Lin S, Zhang XE,Bi L*. The β2 clamp in the Mycobacterium tuberculosis DNA polymerase III αβ2ε replicase promotes polymerization and reduces exonuclease activity.Sci Rep. 2016 Jan 29;6:18418.

8. Zhang XL, Li DF, Fleming J, Wang LW, Zhou Y, Wang DC, Zhang XE,Bi LJ*. Core component EccB1 of the Mycobacterium tuberculosis type VII secretion system is a periplasmic ATPase.FASEB J. 2015 Dec;29(12):4804-14.

9. 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 Dec 24;9(6):2317-29.

10. 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.Nat Genet. 2013 Oct;45(10):1255-60.

11. Li WJ, Li DF, Hu YL, Zhang XE,Bi LJ, Wang DC. Crystal structure of L,D-transpeptidase LdtMt2 in complex with meropenem reveals the mechanism of carbapenem against Mycobacterium tuberculosis.Cell Res. 2013 May;23(5):728-31.

12. 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 Feb 1;41(4):2370-81.

(From Lijun Bi, November 2, 2021)