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杜茁


杜茁,博士,研究员,博士生导师
 
        2003-2008年,中国农业大学,生物学院,生物化学与分子生物学专业(李宁实验室),理学博士;
        2008-2009年,Albert Einstein College of Medicine,细胞生物学系(Carl Schildkraut),博士后;
        2009-2014年,Memorial Sloan Kettering Cancer Center,发育生物学系(Zhirong Bao),博士后;
        2015年,中国科学院遗传与发育生物学研究所,研究员;
        2017年,获得国家自然科学基金“优秀青年科学基金”资助(细胞谱系分化)
        2023年,获得国家自然科学基金“国家杰出青年科学基金”资助(发育调控的活体原位解析)


研究概述:
        生命构建始于胚胎发育,其正常发生是生命健康的前提。全面系统地理解胚胎发育调控是生命科学最重要、最富挑战性的基础科学问题之一,也为理解发育疾病和实现基于细胞命运操控的细胞治疗奠定理论基础。胚胎发育高度复杂,具有很高的细胞的动态性、调控的多样性、微环境依赖性,因此,若不能实现在活体条件下开展连续、动态和高分辨的解析,发育研究的精准化和系统化重大需求将难以满足。本研究组以秀丽线虫(Caenorhabditis elegans)为高效模型,致力于建立发育调控的活体原位研究新方法,以此开展系统水平和多维度的研究,探索胚胎时空编程和动态调控规律。

        研究组建立并发展了一个融合活体基因标记、高时空分辨成像、自动化细胞追踪和单细胞定量分析为一体的研究体系,实现了非损伤地记录胚胎发育全过程,辨别各个细胞身份、并实时探测细胞的多方面调控过程(我们称之为“4D数字发育”)。该体系实现了在分钟和单细胞的时空精度,全景式解析各个胚胎细胞的发育动态调控过程,推动了发育调控的活体、原位解析。在此基础上,我们正在致力于进一步提升研究方法的广度和深度,实现可解析成千上万个胚胎,分析多个调控过程,从分子、细胞和系统水平解析胚胎发育的调控规律。
 
研究组成员:
 
工作人员
王洋洋(工程师),齐欢(助理研究员)
聘用人员
王子怡(研究助理),王妍(技术员)
研究生
刘瑾仪,丛俞林,周子欣,孙小涵,杨淼泠,白宇川
毕业生
硕士:李小雨(2017),寇雅慧(2020),张昊烨(2023)
博士:樊蓉(2021),肖龙(2021),徐伟娜(2022),赵志广(2022),范渡长江(2023)

代表论文:
# 同等贡献,* 通讯作者
 
Defect-buffering cellular plasticity increases robustness of metazoan embryogenesis.
Xiao L, Fan D, Qi H, Cong Y, Du Z*. Cell Systems. 2022 Aug 17;13(8):615-630.
─系统揭示胚胎在遗传干扰条件下具备自适应和自组织能力以应对细胞异常,在细胞水平增强发育稳固性。
 
A 4D single-cell protein atlas of transcription factors delineates spatiotemporal patterning during embryogenesis.
Ma X#, Zhao Z#, Xiao L#, Xu W, Kou Y, Zhang Y, Wu G, Wang Y, Du Z*. Nature Methods. 2021 Aug;18(8):893-902.
封面文章
Highlighted by a News & Views article in Nature Methods. https://doi.org/10.1038/s41592-021-01219-y
被Genomics Proteomics & Bioinformatics杂志评选为“2021年度中国生物信息学十大进展”
─绘制转录因子单细胞4D蛋白动态表达图谱,初步揭示细胞命运图式建立及分化状态转变的调控规律。
 
Single-cell dynamics of chromatin activity during cell lineage differentiation in Caenorhabditis elegans embryos.
Zhao Z#, Fan R#, Xu W, Kou Y, Wang Y, Ma X, Du Z*. Molecular Systems Biology. 2021 Apr;17(4):e10075 (1-24).
─在单细胞精度和基因组尺度解析染色质活性及其多种发育动态变化基本模式及意义。
 
Multivariable regulation of gene expression plasticity in metazoans.
Xiao L#, Zhao Z#, He F*, Du Z*. Open Biology. 2019 Dec;9(12):190150 (1-16).
─揭示了顺式作用元件和组蛋白修饰调控基因表达的可塑性。
 
Systems properties and spatiotemporal regulation of cell position variability during embryogenesis.
Li X#, Zhao Z#, Xu W, Fan R, Xiao L, Ma X, Du Z*. Cell Reports. 2019 Jan 8;26(2):313-321.e7.
─揭示了细胞表型变异的发育时空特异性。
 
Trans-splicing enhances translational efficiency in C. elegans.
Yang YF#, Zhang X#, Ma X#, Zhao T#, Sun Q, Huan Q, Wu S, Du Z*, Qian W*. Genome Research. 2017 Sep;27(9):1525-1535.
─揭示mRNA反式剪接增强蛋白翻译效率。
 
Digital development: a database of cell lineage differentiation in C. elegans with lineage phenotypes, cell-specific gene functions and a multiscale model.
Santella A, Kovacevic I, Herndon LA, Hall DH, Du Z*, Bao Z*. Nucleic Acids Research. 2016 Jan 4;44(D1):D781-5.
─构建细胞谱系分化的表型组学数据库。
 
The regulatory landscape of lineage differentiation in a metazoan embryo.
Du Z*, Santella A, He F, Shah PK, Kamikawa Y, Bao Z*. Developmental Cell. 2015 Sep 14;34(5):592-607.
─揭示进化保守必需基因对细胞谱系分化的多维度调控。
 
E3 ubiquitin ligases promote progression of differentiation during C. elegans embryogenesis.
Du Z#, He F#, Yu Z, Bowerman B, Bao Z*. Developmental Biology. 2015 Feb 15;398(2):267-79.
─揭示泛素化蛋白降解促进细胞分化状态转变。
 
De novo inference of systems-level mechanistic models of development from live-imaging-based phenotype analysis.
Du Z, Santella A, He F, Tiongson M, Bao Z*. Cell. 2014 Jan 16;156(1-2):359-72.
─建立细胞发育命运解析方法,实现了高通量解析细胞命运抉择的调控模型。
 
Systematic quantification of developmental phenotypes at single-cell resolution during embryogenesis.
Moore JL, Du Z, Bao Z*. Development. 2013 Aug;140(15):3266-74.
─建立线虫胚胎发育单细胞表型定量分析方法。
 
Genome-wide colonization of gene regulatory elements by G4 DNA motifs.
Du Z#, Zhao Y#, Li N*. Nucleic Acids Research. 2009 Nov;37(20):6784-98.
-预测G4 DNA是一类广谱性调控基因转录的结构性元件。
 
Genome-wide analysis reveals regulatory role of G4 DNA in gene transcription.
Du Z#, Zhao Y#, Li N*. Genome Research. 2008 Feb;18(2):233-41.
─预测转录起始位点下游G4 DNA结构元件促进基因转录。
 
 
其他论文:
 
Dynamic chromatin regulatory programs during embryogenesis of hexaploid wheat. Zhao L, Yang Y, Chen J, Lin X, Zhang H, Wang H, Wang H, Bie X, Jiang J, Feng X, Fu X, Zhang X, Du Z, Xiao J. Genome Biology. 2023 Jan 13;24(1):7.
 
Comparative Proteome and Cis-Regulatory Element Analysis Reveals Specific Molecular Pathways Conserved in Dog and Human Brains. Hong H, Zhao Z, Huang X, Guo C, Zhao H, Wang GD, Zhang YP, Zhao JP, Shi J, Wu QF, Jiang YH, Wang Y, Li LM, Du Z, Zhang YQ, Xiong Y. Mol Cell Proteomics. 2022 Aug;21(8):100261.
 
Dogs lacking Apolipoprotein E show advanced atherosclerosis leading to apparent clinical complications. Zhao H, Zhao J, Wu D, Sun Z, Hua Y, Zheng M, Liu Y, Yang Q, Huang X, Li Y, Piao Y, Wang Y, Lam SM, Xu H, Shui G, Wang Y, Yao H, Lai L, Du Z, Mi J, Liu E, Ji X, Zhang YQ. Science China Life Science. 2022 Jul;65(7):1342-1356.
 
Lineage context switches the function of a C. elegans Pax6 homolog in determining a neuronal fate.
Brandt JP, Rossillo M, Du Z, Ichikawa D, Barnes K, Chen A, Noyes M, Bao Z, Ringstad N. Development. 2019 Apr 15;146(8):dev168153.
 
mTOR regulates phase separation of PGL granules to modulate their autophagic degradation.
Zhang G, Wang Z, Du Z, Zhang H*. Cell. 2018 Sep 6;174(6):1492-1506.e22.
 
POS-1 promotes endo-mesoderm development by inhibiting the cytoplasmic polyadenylation of neg-1 mRNA.
Elewa A, Shirayama M, Kaymak E, Harrison PF, Powell DR, Du Z, Chute CD, Woolf H, Yi D, Ishidate T, Srinivasan J, Bao Z, Beilharz TH, Ryder SP, Mello CC*. Developmental Cell. 2015 Jul 6;34(1):108-18.
 
A semi-local neighborhood-based framework for probabilistic cell lineage tracing.
Santella A, Du Z, Bao Z*. BMC Bioinformatics. 2014 Jun 25;15:217.
 
Inverted selective plane illumination microscopy (iSPIM) enables coupled cell identity lineaging and neurodevelopmental imaging in Caenorhabditis elegans.
Wu Y*, Ghitani A, Christensen R, Santella A, Du Z, Rondeau G, Bao Z, Colón-Ramos D, Shroff H. Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17708-13.
 
A hybrid blob-slice model for accurate and efficient detection of fluorescence labeled nuclei in 3D.
Santella A, Du Z, Nowotschin S, Hadjantonakis AK, Bao Z*. BMC Bioinformatics. 2010 Nov 29;11:580.
 
Single-molecule analysis reveals changes in the DNA replication program for the POU5F1 locus upon human embryonic stem cell differentiation.
Schultz SS, Desbordes SC, Du Z, Kosiyatrakul S, Lipchina I, Studer L, Schildkraut CL*. Molecular and Cellular Biology. 2010 Sep;30(18):4521-34.
 
Advanced technologies for genomic analysis in farm animals and its application for QTL mapping.
Hu X, Gao Y, Feng C, Liu Q, Wang X, Du Z, Wang Q, Li N*. Genetica. 2009 Jun;136(2):371-86
 
Extensive selection for the enrichment of G4 DNA motifs in transcriptional regulatory regions of warm blooded animals.
Zhao Y#, Du Z#, Li N*. FEBS Letters. 2007 May 15;581(10):1951-6.
 
研究数据共享及可视化:
进化保守基因的胚胎发育表型组:https://dulab.genetics.ac.cn/single-cell-phenomics/
转录因子单细胞蛋白动态表达图谱:http://dulab.genetics.ac.cn/TF-atlas/
单细胞染色质活性图谱:http://dulab.genetics.ac.cn/chromatin-landscape/
细胞表型变异图像及数据:http://dulab.genetics.ac.cn/data_sharing.html
发育必需基因敲降的细胞分化表型组:http://www.digital-development.org/
 
更新时间:2023-09