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  • 尹延东

  • 职务:助理教授,深圳湾实验室双聘教师

  • 邮箱:yinyd@pku.edu.cn


  • 教育背景及工作经历

     

    2021.09-至今     北京大学深圳研究生院 Tenure-track助理教授
    2021.05-至今       深圳湾实验室 特聘研究员
    2018.08-2021.05   美国纽约大学医学院 研究科学家(Research Scientist)
    2014.03-2018.08   美国纽约大学医学院 博士后 (合作导师:Eli Rothenberg副教授)
    2013.07-2014.03   北京大学化学与分子工程学院 研究助理 (导师:赵新生教授))
    2009.09-2010.01   北京大学化学与分子工程学院,助教
    2010.03-2010.07   北京大学化学与分子工程学院,助教

  • 研究兴趣

     

    1.基于高阶相关函数的图像挖掘技术开发
    多色超分辨显微成像技术为细胞内原位观测生物分子复合物的构造提供了有力工具,其15~40纳米的空间分辨率为观测者呈现出细胞内更多更精细的构造细节。然而,这些复杂细节的呈现为图像的定量分析带来巨大挑战,尤其当所观测的大分子复合体在细胞内广泛、拥挤分布时,观测者很难直接从图像中提取有效定量的信息。针对这一点,我们开发了基于三阶相关函数 (Triple Correlation Function, TCF) 的图像挖掘技术,实现在复杂混沌图像中生物分子复合体的构造模型识别以及相关的定量分析(Nat. Communs., 2019, 第一作者,共同通讯作者)。利用这项技术,我们1) 首次定量分析细胞内DNA复制的监控、调控机制,并揭示其与DNA复制受抑时的应激响应机制的物理关联(Mol. Cell, 2021, 第一作者,共同通讯作者);2) 首次定量分析了细胞内G四聚体在DNA复制叉处的瞬时形成及其对DNA复制的影响(Nat. Communs., 2021, 第二作者)。


    2.活细胞内单分子示踪揭示USP1功能性自切割机制
    USP1是通过对PCNA去泛素化来调控DNA复制的重要因子之一,其通过自切割(auto-cleavage)使得自身失活,从而保证PCNA的泛素化-去泛素化处于动态平衡。然而,USP1自切割导致其自身失活的功能性分子机制尚不得知。活细胞单分子示踪技术理论上可以实时观测单个USP1分子在细胞内的动态,从而解析其分子机制,但由于细胞环境内待测分子往往呈密集分布、自荧光背景噪音高、细胞内单分子示踪极具挑战性。针对这一问题,我们通过在照明和标记两方面的优化实现对细胞核内高密度分布的USP1分子进行单分子示踪。结合双色超分辨显微成像的高分辨定量分析的优势,我们对USP1在DNA复制叉处的空间分布及停留时长的动力学特征进行了定量分析,揭示了USP1自裂解(auto-cleavage)的重要生理学意义之一在于促进USP1从复制叉处的解离,保证复制叉的顺利行进(Nat. Communs., 2022, 共同第一作者)。


    3.降速扩散荧光相关光谱技术的开发
    荧光相关光谱 (Fluorescence Correlation Spectroscopy, FCS) 是一种在热力学平衡状态下测量化学反应速率、分子构象变化动态过程的单分子技术,其原理为在极小的光学探测体积 (如共聚焦显微镜) 内统计微观粒子在系综平衡态附近能量及布居的涨落。然而,受分子本身布朗运动的影响,待测分子无法较长时间停留在微小光点探测区域,使得FCS可探测时间窗口局限于10 ns - 50 µs,极大地限制了FCS的潜在应用范围。为克服分子的布朗运动,保证其有充分长时间停留于观测区域,我们发展了降速扩散荧光相关光谱技术 (Chem. Commun., 2012, 第一作者) 。该技术通过将待测分子固定于较大 (直径约2 µm) 的聚苯乙烯微球来减弱分子的布朗运动,使其在共聚焦光点探测区域内的特征停留时间从原本的~100 µs 延长至~1 s,将FCS的动力学可观测窗口拓展了2-3个数量级。利用该方法,我们对双链DNA中单个错配碱基的自发翻转进行了定量分析,为DNA错配碱基修复机制的研究提供了基本的热动力学依据(PNAS, 2014, 第一作者)。

     

  • 代表性论文

1.M Lu, W Yao, Y Li, D Ma, Z Zhang, H Wang, X Tang, Y Wang, C Li, D Cheng, H Lin, Y Yin*,J Zhao*, G Zhong*, Broadly effective ACE2 decoy proteins protect mice from lethal SARS-CoV-2 infection. Microbiol Spectr. 2023, 11, e0110023 (*co-corresponding)
2.SM Christie, T Tada,
Y Yin, A, Bhardwaj, NR Landau, E Rothenberg, Single-virus tracking reveals variant SARS-CoV-2 splike proteins induce ACE2-independent membrane interations. Sci. Adv. 2022, 8, eabo3977
3.H Xue, A Bhardwaj,
Y Yin, C Fijen, A Ephstein, L Zhang, X Ding, JM Pascal, TL VanArsdale, E Rothenberg, A two-step mechanism governing PARP1-DNA retention by PARP inhibitors. Sci. Adv. 2022, 8, eabp0414
4.KE Coleman#,
Y Yin#, SKL Lui, S Keegan, D Fenyo, DJ Smith, E Rothenberg, TT Huang, USP1-trapping lesions as a source of DNA replication stress and genomic instability. Nat. Communs. 2022, 13, 1740 (#co-first contribution)
5.
Y Yin*,WTC Lee, D Gupta, H Xue, P Tonzi, JA Borowiec, TT Huang, M Modesti, E Rothenberg*, A basal-level activity of ATR links replication fork surveillance and stress response. Mol. Cell 2021, 81, 4243-4257 (*co- corresponding)
6.WTC Lee,
Y Yin, M Morton, P Tonzi, PP Gwo, D Odermatt, M Modesti, S Cantor, K Gari, T Huang, E Rothenberg, Single-molecule imaging reveals replication fork coupled formation of G-quadruplex structures hinders local replication stress signaling. Nat. Commun. 2021, 12, 2525
7.DR Whelan, WTC Lee, F Marks, YT Kong,
Y Yin, E Rothenberg, Super-resolution visualization of distinct stalled and broken replication fork structures. Plos Genetics 2020, 16, e1009256
8.T Trcek, TE Douglas, M Grosch,
Y Yin, WVI Eagle, ER Gavis, H Shroff, E Rothenberg, R Lehmann, Sequence-Independent Self-Assembly of Germ Granule mRNAs into Homotypic Clusters. Mol. Cell 2020, 78, 941-950
9.H Zhang, CL Christensen, R Dries, MG Oser, J Deng, B Diskin, F Li, Y Pan, X Zhang,
Y Yin, …, E Rothenberg, G Miller, NS Gary, KK Wong, CDK7 inhibition potentiates genome instability triggering anti-tumor immunity in small cell lung cancer. Cancer Cell 2020, 37, 37-54.e9
10.F Pessina, F Giavazzi,
Y Yin, …, E Rothenberg, F d’Adda di Fagagna, Functional transcription promoters at DNA double-strand breaks mediate RNA-driven phase separation of damage-response factors. Nat. Cell. Biol. 2019, 21, 1286-1299
11.JC Kim, M Pérez-Hernández, FJ Alvarado, SR Maurya, J Montnach,
Y Yin, …, E Rothenberg, A Lundby, HH Valdivia, M Cerrone, M Delmar, Disruption of Ca2+i homeostasis and connexin 43 hemichannel function in the right ventricle precedes overt Arrhythmogenic Cardiomyopathy in Plakophilin-2-deficient mice. Circulation, 2019, 140, 1015-1030
12.TN Moiseeva,
Y Yin, …, E Rothenberg, SC Watkins, CJ Bakkenist, An ATR and CHK1 kinase signaling mechanism that limits origin firing during unperturbed DNA replication. Proc. Natl. Acad. Sci. U. S. A. 2019, 116, 13374-13383
13.
Y Yin*, WTC Lee, E Rothenberg*, Ultrafast Data Mining of Molecular Assemblies in Multiplexed High-Density Super-Resolution Images. Nat. Commun. 2019, 10, 119 (*co- corresponding)
14.P Tonzi,
Y Yin, WTC Lee, E Rothenberg, TT Huang, Translesion polymerase kappa-dependent DNA synthesis underlies replication fork recovery. eLife 2018, 7, e41426
15.C Nemoz, V Ropars, P Frit, A Gontier, P Drevet, J Yu, R Guérois, A Pitois, A Comte, C Delteil, N Barboule, P Legrand, S Baconnais,
Y Yin, S Tadi, E Barbet-Massin, I Berger, E Le Cam, M Modesti, E Rothenberg, P Calsou, XLF and APLF bind to Ku80 on two remote sites to ensure DNA repair by non-homologous end-joining. Nat. Struct. Mol. Biol. 2018, 25, 971-980
16.D Whelan, WTC Lee,
Y Yin, DM Ofri, K Bermudez-Hernandez, S Keegan, D Fenyö, E Rothenberg, Spatiotemporal dynamics of homologous recombination repair at single collapsed replication forks. Nat. Commun. 2018, 9, 3882
17.J Wang,
Y Yin, S Lau, J Sankaran, E Rothenberg, T Wohland, M Meier-Schellersheim, H Knaut, Anosmin1 Shuttles Fgf to Facilitate Its Diffusion, Increase Its Local Concentration, and Induce Sensory Organs. Dev. Cell 2018, 46, 751-766
18.G Rona, D Roberti,
Y Yin, JK Pagan, H Homer, E Sassani, A Zeke, L Busino, E Rothenberg, M Pagano, PARP1-dependent recruitment of the FBXL10-RNF68-RNF2 ubiquitin ligase to sites of DNA damage controls H2A.Z loading. eLife 2018, 7, e38771
19.K Bermudez-Hernandez, S Keegan, D Whelan, DA Reid, J Zagelbaum,
Y Yin, S Ma, E Rothenberg, D Fenyö, A method for quantifying molecular interactions using stochastic modelling and Super-Resolution microscopy. Sci. Rep. 2017, 7, 14882
20.DA Reid, MP Conlin,
Y Yin, HH Chang, G Watanabe, MR Lieber, DA Ramsden, E Rothenberg, Bridging of double-stranded breaks by nonhomologous end-joining ligation complex is modulated by DNA end chemistry. Nucl. Acids Res. 2017, 45, 1872-1878
21.Y Yin, E Rothenberg, Probing the spatial orgnization of molecular complexes using triple-pair-correlation. Sci. Rep. 2016, 6, 30819
22.H Bi,
Y Yin, B Pan, G Li, XS Zhao, Scanning single-molecule fluorescence correlation spectroscopy enables kinetics study of DNA hairpin folding with a time window from microseconds to seconds. J. Phys. Chem. Lett. 2016, 7, 1865-1871.
23.YH Chen#, MJK Jones#,
Y Yin#, SB Crist, L Colnaghi, RJ Sims, E Rothenberg, PV Jallepalli, TT Huang, ATR-mediated phosphorylation of FANCI regulates dormant origin firing in response to replication stress. Mol. Cell 2015, 58, 323-338 (# co-first contribution)
24.
Y Yin#, L Yang#, G Zheng, C Gu, C Yi, C He, Y Gao, XS Zhao, Dynamics of spontaneous flipping of a mismatched base in DNA duplex. Proc. Natl. Acad. Sci. U. S. A. 2014, 111, 8043-8048 (# co-first contribution)
25.
Y Yin, R Yuan, XS Zhao, Amplitude of Relaxations in Fluorescence Correlation Spectroscopy for Fluorophores that Diffuse Together. J. Phys. Chem. Lett. 2013, 4, 304-309.
26.
Y Yin, P Wang, X Yang, X Li, C He, XS Zhao, Panorama of DNA hairpin folding observed via diffusion-decelerated fluorescence correlation spectroscopy. Chem. Commun. 2012, 48, 7413-7415.
27.X Li,
Y Yin, X Yang, Z Zhi, XS Zhao, Temperature dependence of interaction between double stranded DNA and Cy3 or Cy5. Chem. Phys. Lett. 2011, 513, 271-275.
28.
Y Yin, XS Zhao, Kinetics and Dynamics of DNA Hybridization. Acc. Chem. Res. 2011, 44, 1172-1181 (review).
29.
Y Yin, X Zhou, XS Zhao, Maximum Entropy Method for Analyses of Fluorescence Correlation Spectra of Oligonucleotide Intra-Chain Collision. Acta Phys. Chim. Sin. 2010, 26, 1087-1092.

 

职务 助理教授,深圳湾实验室双聘教师 电话
邮箱 yinyd@pku.edu.cn