Zhongjun Qin

Personal Information

Principal Investigator
Researcher
Email:qin@sibs.ac.cn
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Research Direction

Research Unit

Key Laboratory of Synthetic Biology, CAS

Zhongjun Qin

Personal Profile

016- Director of the CAS Key Laboratory of Synthetic biology

2004-2009 Director of Laboratory of Molecular Microbiology

2002-2004 Director of Laboratory of Molecular Regulation for Microbial Secondary Metabolism

2001- Full professor, Shanghai Institute of Plant Physiology and Ecology, the Chinese Academy of Sciences

1995-2001 Post-doctoral fellow and visiting scientist, Laboratory of professor Stanley N. Cohen, Department of Genetics, Stanford University

1994-1995 Associate professor, Huazhong Agricultural University

1993-1994 Assistant professor, Huazhong Agricultural University

1987-1992 Huazhong Agricultural University Ph. D. Microbiology

1983-1987 Wuhan University B. Sc. Microbiolog

Research Work

Synthetic biology was initiated in year 2000 by several USA scientists who had backgrounds of physics and engineer. They thought that the extremely complicated biological systems could be systematic designed and reconstructed engineeringly by the standardized biological devices such as parts, modules and circuits. They have successfully constructed different regulatory gene circuits in organisms, novel pathways for producing chemicals (e.g., artemisinin), even chemical synthesis of the prokaryote Mycoplasma chromosome (i.e. ~1 Mb) and the eukaryote Saccharomyces cerevisiae chromosomes (5 of 16). However, it is unknown that if synthetic biology could also be applied for basic biological researches and to answer important biological questions which classic molecular biologists have hardly addressed. My laboratory is interested in combining the 'hypothesis-driven' of classical molecular biology and the 'engineer-driven' of synthetic biology to address some fundamental biological questions, e.g., chromosome numbers and evolution, chromosome structure and genome function, linear and circular chromosomes etc. Obviously, we choose the prokaryotic model Escherichia coli and the unicellular eukaryote model Saccharomyces cerevisiae.

Main Achievements

During the years 2013~2018, my laboratory has focused on creating both single linear and circular chromosome yeasts by using the unicellular eukaryote model Saccharomyces cerevisiae and their characterizations including cell biology, genetics especially chromosome three dimensional structures. We also developed several technological tools for synthetic biology, including CasHRA (Cas9-facilitated Homologous Recombination Assembly) and MEGA (Multiple Essential Genes Assembling) methods.

The natural system of organisms can be classified into prokaryotes (including eubacteria and archaea) and eukaryotes, according to their fundamental cell structure. All known natural eukaryotic cells have multiple linear chromosomes, for examples, the budding yeast Saccharomyces cerevisiae has 32 chromosomes, the fruit fly Drosophila melanogaster has 8 chromosomes, the model plant Arabidopsis thaliana has 10 chromosomes, the mouse Mus musculus has 40 chromosomes, and humans (Homo sapiens) have 46 chromosomes. Prokaryotic cells usually contain a chromosome of a circular structure. We hypothesized that eukaryotes might be artificially created like a prokaryote, which organize all genetic material in a single linear chromosome and carry out the normal cellular functions. We customized the artificial single-chromosome yeast with “engineering precision design” and established the guiding principles and rational experimental design of the overall program. We have tried and developed an efficient chromosome fusion method since 2013. In year 2016, a Saccharomyces cerevisiae strain SY14 with only one linear chromosome and SY15 with one circular chromosome were successfully created. Since this is my first time to study on yeast, we further cooperated with a yeast expert professor Zhou Jinqiu’s lab to characterize strains SY14 and SY15, Wuhan Frasergen Gene Information Company performed the three-dimensional structure of its chromosomes. We found that although the three-dimensional structure of the artificially created single linear chromosome has undergone dramatic changes, SY14 cell has normal cellular functions, which subverts the traditional concept of chromosome three-dimensional structure determining the spatiotemporal expression of genes, revealing a new relationship of the chromosomal three-dimensional structure and cell functions. We summarized all the SY14 works in a manuscript and submitted it to “Nature” on September 29, 2107 and was finally published on August 1, 2018. We also created a single circular chromosome yeast SY15 in year 2016. SY15 and SY14 cells were similar in both size and shape, however, a slightly higher ratio of abnormal long-shape cells was observed in SY15. Interestingly, we deleted the TLC1 gene, which encodes the RNA template component of telomerase and is essential for telomere replication, and found that SY15 cells could bypass the telomerase-dependent senescence. The SY15 works was published on “Cell Research” (2019).

This research achievement is a new example of exploring major fundamental scientific issues in the origin and evolution of life. The "birth" of single-chromosome yeast is thought as that after the synthesis of bovine insulin and tRNA in the 1960s in Shanghai, Chinese scholars once again used synthetic science strategies to answer an important question in the field of life sciences. A major fundamental issue is the establishment of a bridge between genomic evolution between prokaryotes and eukaryotes. This is a vivid manifestation of the concept of “construction to understand” in synthetic biology.

New tools are important for development of synthetic biology. We have published (also patented) several technological methods since 2015, including CasHRA (Cas9-facilitated Homologous Recombination Assembly) method for constructing megabase-sized DNA, MEGA (Multiple Essential Genes Assembling) method for chromosomal large segment (e.g., >200 kb) deletion and CRISPR-Cas9 facilitated multiple-chromosome fusion method. These methods were published on “Nucleic Acids Research” (2016), “ACS Synthetic Biology” (2015, 2018) and “Nature Protocols” (2019).

Publications

1. Yangyang Shao, Ning Lu, Xiaoli Xue* and Zhongjun Qin* (2019). Creating functional chromosome fusions in yeast with CRISPR–Cas9. Nature Protocols. 14:2521–2545.

2. Yangyang Shao, Ning Lu, Chen Cai, Fan Zhou, Shanshan Wang, Zhihu Zhao*, Guoping Zhao*, Jinqiu Zhou*, Xiaoli Xue* and Zhongjun Qin* (2019). A single circular chromosome yeast. Cell Research. 29:87–89.

3. Yangyang Shao, Ning Lu, Zhenfang Wu, Chen Cai, Shanshan Wang, Ling-Li Zhang, Fan Zhou, Shijun Xiao, Lin Liu, Xiaofei Zeng, Huajun Zheng, Chen Yang, Zhihu Zhao, Guoping Zhao*, Jinqiu Zhou*, Xiaoli Xue* and Zhongjun Qin* (2018) Creating a functional single chromosome yeast. Nature (article). 560:331–335.

4. Yangyang Shao, Ning Lu, Zhongjun Qin* and Xiaoli Xue* (2018). CRISPR-Cas9 facilitated multiple-chromosome fusion in Saccharomyces cerevisiae. ACS Synthetic Biology. 7(11): 2706–2708.

5. Jianting Zhou, Ronghai Wu, Xiaoli Xue* and Zhongjun Qin* (2016) CasHRA (Cas9-facilitated Homologous Recombination Assembly) method of constructing megabase-sized DNA. Nucleic Acids Research. 4(14):e124.

6. Xiaoli Xue*, Tao Wang, Peng Jiang, Yangyang Shao, Min Zhou, Li Zhong, Ronghai Wu, Jianting Zhou, Haiyang Xia, Guoping Zhao and Zhongjun Qin* (2015) MEGA (Multiple Essential Genes Assembling) deletion and replacement method for genome reduction in Escherichia coli. ACS Synthetic Biology. 4(6):700–706.