师资队伍 | 张数一, PhD

张数一

博士,助理教授

张数一博士2009获得清华大学学士学位,2015年获得美国宾夕法尼亚州立大学博士学位,导师是Donald Bryant教授。2015年至2019年在美国麻省理工学院进行博士后研究,合作导师是ACS Synthetic Biology杂志主编Christopher Voigt教授,并与哈佛大学David Liu教授实验室展开积极合作,将噬菌体辅助的连续定向进化系统广泛地应用于合成生物学的研究。2019年加入清华大学药学院,担任教研系列助理教授。


研究方向

合成生物学作为生命科学和工程科学相结合的前沿交叉学科,在医药、环境、健康等领域都有巨大的潜在应用价值。合成生物学的主要研究目标是用工程化的方法设计复杂可控的生命系统。张数一实验室长期致力于合成生物学关键领域的研究,聚焦在代谢通路、能量摄取、调控网络等领域,相关研究成果发表在Science,Nature Biotechnology,Nature Microbiology,Nucleic Acids Research,Metabolic Engineering等顶级学术期刊。针对这些合成生物学的关键方向,目前课题组侧重在优良蛋白质元件的计算机辅助从头理性设计、自动化平台赋能的高通量表征、连续定向进化系统辅助的快速精准优化等,以及将这些设计和改造后的蛋白质元件有机耦合基因线路,搭建生物系统,有效地应用于疾病诊断和治疗等领域。


科学贡献

1、代谢通路:研究成果解决了困扰蓝细菌科学界接近半个世纪的有关三羧酸循环的难题,彻底改变了科学界对蓝细菌中心代谢通路的认识。这个研究成果已被世界经典教科书《Brock Biology of Microorganisms》第14版第3章作为封面收录。
2、能量摄取:我们与合作者共同发现了能利用远红光的光合系统,拓展了光合作用的潜能,被英国皇家科学院院士 Bill Rutherford教授称为改变教科书式的新发现。
3、调控网络:实现了复杂调控网络的自动化设计,编辑细胞进行逻辑运算,成功构建了能显示7段数码管的工程菌。自动化设计并改进了基于CRISPR系统的调控网络,实现了肠道微生物的基因回路运算。

荣誉和奖励

国家高层次人才计划青年项目
国家优秀自费留学生奖
宾夕法尼亚州立大学优秀博士论文奖

代表性论文

1. Shuyi Zhang and Donald A. Bryant. (2011). The tricarboxylic acid cycle in cyanobacteria. Science, 334, 1551-1553, DOI: 10.1126/science.1210858 - This work was featured as cover story in Chapter 3 of the classic microbiology textbook Brock Biology of Microorganisms (14th Edition).
2. Kenchappa G. Kumaraswamy, Xiao Qian, Tiago Guerra, Shuyi Zhang, Donald A. Bryant and Charles G. Dismukes. (2013). Reprogramming the glycolytic pathway for increased hydrogen production in cyanobacteria: metabolic engineering of NAD+-dependent GAPDH. Energy & Environmental Science, 6(12):3722-3731, DOI: 10.1039/C3EE42206B.
3. Shuyi Zhang, Gaozhong Shen, Zhongkui Li, John H. Golbeck and Donald A. Bryant. (2014). Vipp1 is essential for the biogenesis of Photosystem I but not thylakoid membranes in Synechococcus sp. PCC 7002. Journal of Biological Chemistry, 289(23), 15904-15914, DOI: 10.1074/jbc.M114.555631.
4. Fei Gan, Shuyi Zhang, Nathan C. Rockwell, Shelley S. Martin, Clark J. Lagarias and Donald A. Bryant. (2014) Extensive remodeling of a cyanobacterial photosynthetic apparatus in Far-Red light. Science, 345, 1312-1317, DOI: 10.1126/science.1256963 - This work was described as “text book changing stuff” by Professor Bill Rutherford from Imperial College London.
5. Hans C. Bernstein, Allan Konopka, Matthew R. Melnicki, Eric A. Hill, Leo A. Kucek, Shuyi Zhang, Gaozhong Shen, Donald A. Bryant and Alexander S. Beliaev. (2014) Effect of mono- and dichromatic light quality on growth rates and photosynthetic performance of Synechococcus sp. PCC 7002. Frontiers in Microbiology, 5, 488, DOI: 10.3389/fmicb.2014.00488.
6. Shuyi Zhang and Donald A. Bryant. (2014) Learning new tricks from an old cycle: the TCA cycles of cyanobacteria, algae and plants. Perspectives in Phycology, 2, 73-86, Invited review article, DOI: 10.1127/pip/2014/0016.
7. Shuyi Zhang and Donald A. Bryant. (2015) Biochemical validation of the the glyoxylate cycle in the cyanobacterium Chlorogloeopsis fritschii PCC 9212, Journal of Biological Chemistry 290 (22), 14019-14030, DOI: 10.1074/jbc.M115.648170.
8. Shuyi Zhang, Yang Liu and Donald A. Bryant. (2015) Metabolic engineering of Synechococcus sp. PCC 7002 to produce poly-3-hydroxybutyrate and poly-3-hydroxybutyrate-co-4-hydroxybutyrate, Metabolic Enginneering, 32, 174-183, DOI: 10.1016/j.ymben.2015.10.001.
9. Xiao Qian, Kenchappa G. Kumaraswamy, Shuyi Zhang, Colin Gates, Donald A. Bryant and Charles G. Dismukes. (2015) Inactivation of nitrate reductase alters metabolic branching of carbohydrate fermentation in the cyanobacterium Synechococcus sp. strain PCC 7002. Biotechnology & Bioengineering, 113(5):979-988, DOI: 10.1002/bit.25862.
10. Anagha Krishnan, Shuyi Zhang, Yang Liu, Kinan A Tadmori, Donald A Bryant and G Charles Dismukes (2015) Consequences of ccmR deletion on respiration, fermentation and H2 metabolism in cyanobacterium Synechococcus sp. PCC 7002. Biotechnology & Bioengineering, 113(7):1448-1459, DOI: 10.1002/bit.25913.
11. Shuyi Zhang, Xiao Qian, Shannon Chang, G Charles Dismukes and Donald A Bryant (2016) Natural and synthetic variants of the tricarboxylic acid cycle in cyanobacteria: introduction of the GABA shunt into Synechococcus sp. PCC 7002. Frontiers in Microbiology, 7, 1972, DOI: 10.3389/fmicb.2016.01972.
12. Shuyi Zhang and Christopher A. Voigt. (2018) Engineered dCas9 with reduced toxicity in bacteria: implications for genetic circuit design. Nucleic Acids Research, gky884, DOI: 10.1093/nar/gky884.
13. Kenchappa G Kumaraswamy, Anagha Krishnan, Gennady Ananyev, Shuyi Zhang, Donald A. Bryant and G Charles Dismukes. (2019) Crossing the Thauer limit: Rewiring Cyanobacterial Metabolism to Maximize Fermentative H2 Production. Energy & Environmental Science, 12, 1035-1045, DOI: 10.1039/C8EE03606C.
14. Jonghyeon Shin, Shuyi Zhang, Bryan S. Der, Alec A.K. Nielsen, and Christopher A. Voigt. (2020) Programming Escherichia coli to function as a digital display. Molecular Systems Biology, 16: e9401, DOI: 10.15252/msb.20199401. Highlighted as Cover Article.
15. Mao Taketani, Jianbo Zhang, Shuyi Zhang, Alexander J. Triassi, Yu-Ja Huang, Linda G. Griffith & Christopher A. Voigt. (2020) Genetic circuit design automation for the gut resident species Bacteroides thetaiotaomicron. Nature Biotechnology, DOI: 10.1038/s41587-020-0468-5.
16. Ye Chen, Shuyi Zhang, Eric M. Young, and Christopher A. Voigt. (2020) Genetic circuit design automation for yeast. Nature Microbiology, In minor revision.