Molecular Biology of Haloarchaea and Genome Editing
Principal Investigator:
Dr. Prof. Hua Xiang
Director of SKLMR;
Deputy Director-General of IMCAS
Tel/Fax:010-64807472
E-mail: xiangh@im.ac.cn
Research Area:
Archaea Genetics, CRISPR-Cas system, Genome Editing, Bioplastic Production, Environmental Microbiome.
Research Interests:
Haloarchaea are a distinct evolutionary branch of the Archaea (the third domain of life on Earth). They require high salt concentrations for optimal growth, and thrive in salt lakes, sea salterns and many other hypersaline environments. The research in our laboratory has focused on genetics and metabolism of haloarchaea for more than 15 years. Currently, the researches in our laboratory include but not limited to the halophilic archaea, we are particularly interested in:
For the two haloarchaeal model strains, Haloarcula hispanica and Haloferax mediterranei, we have already determined their complete genome sequences (JB 2011, JB 2012), and have also established efficient genetic manipulation systems (JGG 2011). Especially for H. hispanica, a much more efficient genome editing pipeline based on its native CRISPR was recently developed (JGG 2017).
In the research of haloarchaeal metabolism, we have identified and characterized for the first time the key enzymes and pathways involved in biosynthesis of the bioplastic PHA in halophilic archaea, including characterization of the haloarchaeal PHA synthases (AEM 2007, JB 2008a, AEM 2010), PHA-specific β-Ketothiolases (AEM 2013a) and acetoacetyl-CoA reductases (AEM 2009), and the PHA granule-associated proteins (AEM 2012, AEM 2015) that are involved in regulation of PHA granule formation in haloarchaea. Multiple propionyl-CoA supplying pathways for poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) (PHBV) production (AEM 2013b) and the relationship between PHBV biosynthesis and central metabolism (JPR 2013, AMB 2013) have also been demonstrated. Recently, PHBV mobilization (AEM 2015a, Sci Rep 2016) and its linkage to haloarchaeal-specific acetyl-CoA and propionyl-CoA assimilation (ISME J 2016, AEM 2015b) were also illuminated. In addition, we showed that tailor-made haloarchaea-produced PHBV exhibited unique material properties and had extremely low endotoxin concentration (Biomacromolecules 2015). These bioplastic polymers possessed superior biocompatibility (Biomaterials 2017) and accelerated wound healing process when decorated with antimicrobial peptides (Biomaterials 2018). These progresses may provide novel insights for future economical production of industry-scale bioplastic PHAs or tailor-made PHAs by haloarchaea.
For genetics research of haloarchaea, we have characterized the multiple replication origins of the haloarchaeal replicons and their potential control mechanisms (NAR 2014a, BMC Genomics 2012, FM 2014, GBE 2014). We have reported for the first time the activation of a dormant origin in haloarchaeal chromosome (NC 2015), and have also identified the conserved double-strand origins (DSO) for haloarchaeal RCR plasmids (JB 2008b). We have also reported a new paradigm for archaeal gene regulation directed by general transcription factors (NAR 2008), and investigated the transcriptional as well as post-transcriptional mechanisms involved in the PTS regulation in haloarchaea (AEM 2014).
Using haloarchaeal CRISPR systems, a series of critical general issues about the mysterious adaptation pathway were successively addressed, including the importance role of the priming mechanism (NAR 2014b), the self vs. non-self discrimination strategy (NAR 2014c), the DNA motifs that determine accurate repeat duplication (NAR 2016), and the sequence factors deciding the spacer size (NAR 2017). A CRISPR–independent Cas6-cleavage-mediated provirus inhibition (JB 2013) was also revealed. Furthermore, we developed the first highly efficient CRISPR-based genome editing pipeline for the polyploid haloarchaeal species (JGG 2017). In summary, these studies will not only provide novel insights into the CRISPR-virus interactions and the haloarchaeal genome stability, but also promote the development of new genetic tools.
Currently, although our researches are still focused on the molecular biology of haloarchaea and related microbial resources, some of our projects have started to shift from single strain to microbiome, from CRISPR mechanism to genome editing system innovation, from bioplastic synthesis to biodegradation of synthetic plastics, etc. which was expected to promote the transformation from basic research to biotechnological application.
These projects were funded by grants from the National Natural Science Foundation of China, the Ministry of Science & Technology of China, and the Chinese Academy of Sciences.
Group Members:
Principal Investigator
Prof. Dr. Hua Xiang
Prof. of Molecular Microbiology,
Institute of Microbiology, Chinese Academy of Sciences, No.1 West Beichen Road, Chaoyang District,
Beijing 100101, P. R. China
Tel/ Fax: 86-10-64807472
E-mail: xiangh@sun.im.ac.cn ; xiangh@im.ac.cn
Major and Specialty
Molecular Microbiology; Genetics, Physiology and Biotechnology of Archaea
Position
Professor and Director of State Key Laboratory of Microbial Resources (SKLMR), Director-General of Institute of Microbiology, Chinese Academy of Sciences (IMCAS)
Education
B.S. 1991 Biology, Beijing Normal University
M.S. 1994 Genetics, Beijing Normal University
Ph.D 1997 Biochemistry & Molecular biology, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS&PUMC)
Postdoctoral Fellow Training
1997-1999 Dr. H. Tan’s Lab., Institute of Microbiology, Chinese Academy of Sciences, Beijing, China;
1999-2001 Dr. David WC Li’s Lab., University of Medicine & Dentistry of New Jersey (UMDNJ), New Jersy, U.S. A.
Professional Appointments
2001-2003 Principal Investigator and Associate Professor, IMCAS
2009 Awardee of the National Distinguished Young Scholar Program, China.
2003.12-present Principal Investigator, Professor and Ph.D Advisor, IMCAS
Editorial Board
Journal of Genetics and Genomics (Associate editor)
Frontiers in Microbiology (Associate editor)
Frontiers in Genome Editing (Associate Editor)
Acta Laser Biology Sinica (Associate Editor)
Applied and Environmental Microbiology (Editorial Board member)
The Innovation (Editorial Board member)
Permanent Staffs
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Jian Zhou |
Jing Han |
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Ming Li Research Interest: Genetics |
Dahe Zhao Research Interest:Biotechnology |
Postdoctoral Fellows
Luyao Gong, 2020-
Tong Yu, 2019-
Heng Zhou, 2019-
Sumit Kumar, 2016- 2018
Shaoxing Chen, 2014-2016
Shiqiong Chen, 2004-2006
Graduate Students
Junyu Chen (Ph. D student)
Qiong Xue (Ph.D student)
Feiyue Cheng (Ph. D student)
Shengjie Zhang (Ph. D student)
Kaixin Du (Ph. D student)
Ruchira Mitra (Ph. D student)
Lin Lin (M. Sc student)
Jing Guo (M. Sc student)
Manqi Zhang (M. Sc student)
Undergraduates
Zhuowen Li (University of Chinese Academy of Sciences)
Former Graduate Students
Zhenqiang Zuo (2019, Ph. D)
Luyao Gong (2019,Ph. D)
Feiyue Cheng (2018 M. Sc)
Haibo Yang (2017 Ph.D)
Xiongjian Jiang (2017 M. Sc)
Rui Wang (2016 Ph. D)
Xiaobin Liu (2016 M. Sc)
Guiming Liu (2016 Ph. D)
Jing Hou (2015 Ph. D)
Shuangfeng Cai (2015 Ph.D)
Ming Li (2014 Ph.D)
Zhenfang Wu (2014 Ph. D)
Lei Cai (2014 Ph. D)
Jinhua Wu (2014 M.Sc)
Xiaoqing Liu (2013 Ph.D)
Hailong Liu (2012, Ph.D)
Dahe Zhao (2012, M.Sc, 2017 Ph. Sc)
Jie Li (2010, Ph.D)
Bo Feng (2010, M.Sc. )
Jingfang Liu (2009, Ph.D)
Di Miao (2009, M.Sc.)
Qiuhe Lu (2009, Ph.D)
Ligang Zhou (2008, Ph.D)
Shuangshuang Mei (2008, Ph.D)
Jing Han (2008, Ph.D)
Huadong Pei (2007, Ph.D)
Chaomin Sun (2006, Ph.D)
Meixian Zhou (2005, Ph.D)
Yun Li (2004, Ph.D)
Yuanyuan Ren (2004, M.Sc.)
Jian Zhang (2003, M.Sc.)
Former Staff
Zhihong Xie(2005)
Fan Zhang (2009-2011)
Lei Wang(2012-2015)
Jingfang Liu(2001-2018)
Postdoctoral Position:
Positions for Postdoctoral scholars and Ph.D students are available. For application, please contact Prof. Dr. Hua Xiang at xiangh@im.ac.cn.
Representative Pictures
Three steps and the delicate molecular specificities during primed CRISPR adaptation.
(Nucleic Acids Res. 2014, 42(4): 2483-92; Nucleic Acids Res. 2014, 42(11): 7226-35;
Nucleic Acids Res. 2016, 44(9): 4266–77; Nucleic Acids Res. 2017, 45(8): 4642-54)
Activation of dormant replication origins in haloarchaea.
(Nature Communications, 2015, 6:8321)
Biosynthesis of tailor-made PHBHV by Haloarchaea and its superior biocompatibility.
(Biomaterials, 2017,139:172-186)
Identification of the four pathways for propionyl-CoA synthesis in H. mediterranei.
(Applied and Environmental Microbiology, 2013, 79(9): 2922-31)
Regulation of the PHBV accumulation and granule formation by PhaR and PhaP in H. mediterranei
( Applied and Environmental Microbiology, 2012, 78(6):1946-1952;
Applied and Environmental Microbiology, 2015, 81(1):373-85)
Recent Publications
[2020]
[2013]
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English