人工细胞的表型测试与分选:构建从光谱学到遗传学的桥梁
Phenotyping and Sorting of Synthetic Cells: Building Bridge from Spectroscopy to Genetics
Phenotyping and Sorting of Synthetic Cells: Building Bridge from Spectroscopy to Genetics
作者
马波(中国科学院青岛生物能源与过程研究所 单细胞中心 青岛 266101)
徐健(中国科学院青岛生物能源与过程研究所 单细胞中心 青岛 266101)
徐健(中国科学院青岛生物能源与过程研究所 单细胞中心 青岛 266101)
中文关键词
合成生物学;表型测试;分子光谱;光谱激活细胞分选;单细胞表型组;单细胞功能基因组
英文关键词
synthetic biology;phenotype test;molecular spectroscopy;cell sorting;single-cell phenome;single-cell functional genomics
中文摘要
近年来，基因组测序、编辑与合成技术日新月异，推动了基因型“设计”和“合成”能力的突飞猛进，同时也使人工细胞的表型检测成为合成生物学发展的瓶颈环节之一。对于细胞功能的快速测试与评价，单细胞分析技术具有重要意义与前景，但理想的解决方案需要具备活体无损、非标记式、提供全景式表型、能分辨复杂功能、快速高通量且低成本、能与组学分析联动等特征。以此为出发点，文章重点介绍了基于非标记式分子光谱学的单细胞功能表征、分选与组学技术体系的进展，并讨论了该领域的关键问题与发展方向。多种光谱技术之间扬长避短的运用与多模态成像，结合高通量的光谱激活细胞分选技术及下游单细胞组学技术，正构建与拓展着一条连接光谱学与遗传学的广阔桥梁。这一桥梁不仅为细胞工厂的高通量、全景式表型检测与筛选提供全新的解决方案，还将推动“单细胞精度的光谱表型组-功能基因组”作为一种新的生物大数据类型，服务于“数据科学”驱动下的合成生物技术。
英文摘要
In synthetic biology, the dazzling methodological innovations in sequencing, editing and synthesis of genomes have resulted in an unprecedented capability in "design and manufacturing of genotype". On the other hand, "testing of cellular phenotype and function" has increasingly become one major bottleneck. Single-cell technologies have tremendous implications and potentials in rapid testing of cellular function. However, ideally, such single-cell methods should allow non-invasive live-cell probing, be label-free, provide landscapelike phenotyping capability, distinguish complex functions, operate with high speed, sufficient throughput and low-cost, and finally, be able to couple with downstream omics analysis via cell sorting. In this perspective article, we focus on recent progress in label-free molecular spectroscopy-activated phenotyping, sorting and sequencing of single-cells, and discuss the key challenges and emerging trends of the area. We propose that alliance among the array of non-invasive spectroscopy methods or modes, when coupled with downstream high-throughput cell sorting and omics profiling, will establish and broaden a bridge that connects spectroscopy and genetics, in science, technologies, and communities. This bridge will lead to novel and creative solutions to high-throughput, landscape-like testing and screening of synthetic cells. Moreover, it will fulfill the promise of spectroscopy-enabled single-cell "phenome-genome" as a new type of biological big-data, and accelerate the pace of "data-driven" synthetic biology.
DOI10.16418/j.issn.1000-3045.2018.11.007
作者简介
马波 中国科学院青岛生物能源与过程所单细胞中心微流控系统团队负责人,研究员。2008年在中国科学院大连化学物理研究所微流控芯片实验室获分析化学专业博士学位。2008年5月-2012年7月先后在美国加州大学洛杉矶分校Crump分子成像研究所和莱斯大学等研究机构从事博士后研究。2012年加入中国科学院青岛生物能源与过程研究所。自2003年起致力于微流控芯片技术在分析化学和生命科学中的基础和应用研究。目前研究方向聚焦在:基于微流控高通量单细胞分析技术和仪器研究,以及工业酶、菌株和微藻的高通量筛选、选育和定向进化等。
E-mail:mabo@qibebt.ac.cn
MA Bo Lead of Microfluidic Systems Group at Single-Cell Center,Qingdao Institute of Bioenergy and Bioprocess,Chinese Academy of Sciences (CAS-QIBEBT).He obtained Ph.D.in Analytical Chemistry from Dalian Institute of Chemical Physics,Chinese Academy of Sciences in 2008.From 2008 to 2012,he worked as postdoctoral research associate in UCLA and then Rice University.In 2012,he joined CAS-QIBEBT as a full-time faculty member.His research interest focuses on microfluidics and lab-on-a-chip,in particular microfluidic-based high-throughput single cell sorting and genomics,POCT,etc.He has published over 20 peer-reviewed papers on Analytical Chemistry,Lab on a Chip,etc.,and is listed on 20 patents or patent applications.
E-mail:mabo@qibebt.ac.cn
徐健 中国科学院青岛生物能源与过程研究所单细胞中心功能基因组团队负责人、单细胞中心主任,研究员。2003年获美国圣路易斯华盛顿大学计算机硕士和生物化学博士,2004-2008年任华盛顿大学基因组研究院基因组拼装与分析团队负责人,2008年全职加入中国科学院青岛生物能源与过程研究所。主要通过开发工业微藻合成生物技术、拉曼组技术、微生物组数据科学工具、单细胞分析仪器系列等,服务于光合生物燃料、微生态健康、海洋监测、生物安全等应用领域。发表论文100余篇,被引用近8 000次。任mSystems高级编辑等。
E-mail:xujian@qibebt.ac.cn
XU Jian Lead of Functional Genomics Group and Director of Single-Cell Center,Qingdao Institute of Bioenergy and Bioprocess,Chinese Academy of Sciences (CAS-QIBEBT).He obtained M.S.in Computer Science and Ph.D.in Biochemistry in 2003 from Washington University in St Louis.From 2004 to 2008 he served as Team Lead of Genome Assembly and Analysis at Genome Institute and Research Instructor at Department of Genetics in Washington University.In 2008 he joined CAS-QIBEBT as a full-time faculty member.His research interest includes synthetic biology of industrial microalgae,ramanome technology,microbiome data science and single-cell analysis instrument series.He has published over 100 peer-reviewed papers on Science,Cell Host Microbe,Nature Communications,Plant Cell,etc,with nearly 8 000 citations.He is a senior editor of mSystems.
E-mail:xujian@qibebt.ac.cn
E-mail:mabo@qibebt.ac.cn
MA Bo Lead of Microfluidic Systems Group at Single-Cell Center,Qingdao Institute of Bioenergy and Bioprocess,Chinese Academy of Sciences (CAS-QIBEBT).He obtained Ph.D.in Analytical Chemistry from Dalian Institute of Chemical Physics,Chinese Academy of Sciences in 2008.From 2008 to 2012,he worked as postdoctoral research associate in UCLA and then Rice University.In 2012,he joined CAS-QIBEBT as a full-time faculty member.His research interest focuses on microfluidics and lab-on-a-chip,in particular microfluidic-based high-throughput single cell sorting and genomics,POCT,etc.He has published over 20 peer-reviewed papers on Analytical Chemistry,Lab on a Chip,etc.,and is listed on 20 patents or patent applications.
E-mail:mabo@qibebt.ac.cn
徐健 中国科学院青岛生物能源与过程研究所单细胞中心功能基因组团队负责人、单细胞中心主任,研究员。2003年获美国圣路易斯华盛顿大学计算机硕士和生物化学博士,2004-2008年任华盛顿大学基因组研究院基因组拼装与分析团队负责人,2008年全职加入中国科学院青岛生物能源与过程研究所。主要通过开发工业微藻合成生物技术、拉曼组技术、微生物组数据科学工具、单细胞分析仪器系列等,服务于光合生物燃料、微生态健康、海洋监测、生物安全等应用领域。发表论文100余篇,被引用近8 000次。任mSystems高级编辑等。
E-mail:xujian@qibebt.ac.cn
XU Jian Lead of Functional Genomics Group and Director of Single-Cell Center,Qingdao Institute of Bioenergy and Bioprocess,Chinese Academy of Sciences (CAS-QIBEBT).He obtained M.S.in Computer Science and Ph.D.in Biochemistry in 2003 from Washington University in St Louis.From 2004 to 2008 he served as Team Lead of Genome Assembly and Analysis at Genome Institute and Research Instructor at Department of Genetics in Washington University.In 2008 he joined CAS-QIBEBT as a full-time faculty member.His research interest includes synthetic biology of industrial microalgae,ramanome technology,microbiome data science and single-cell analysis instrument series.He has published over 100 peer-reviewed papers on Science,Cell Host Microbe,Nature Communications,Plant Cell,etc,with nearly 8 000 citations.He is a senior editor of mSystems.
E-mail:xujian@qibebt.ac.cn
