照亮活细胞中的“暗物质”——固有无序蛋白

我们的科研团队致力于探索活细胞中生物大分子的动态过程和作用机理，尤其专注于固有无序蛋白（Intrinsically Disordered Protein，IDP）的生物学特性以及其在神经退行性疾病等多个生物过程中的关键作用。在高等生物体的蛋白质组中，超过40%的蛋白都包含固有无序区域，它们在神经退行性疾病、基因调控、信号传导和病毒感染等方面发挥着重要功能。与折叠的蛋白质不同，固有无序蛋白具有高度无序、局部移动性和高动态性的特点。这些特性使得传统的生物物理技术难以在活细胞内解析其动态作用。因此，固有无序蛋白被称为活细胞中的“暗物质”。为了解决这一挑战，我们的研究团队致力于系统性地开发多个新的交叉融合生物技术，包括超分辨动态成像、基因编码扩展和微流控芯片等先进工具，旨在揭示活细胞中固有无序蛋白的实时动态作用。利用这些交叉融合的生物技术，我们的研究不仅有望为神经退行性疾病的治疗提供新的生物医学策略，还为理解固有无序蛋白在其他生物过程中的功能和机制打开新的视角。

2026年-2029年  国家自然科学基金“细胞生物学基础研究青年专项”　主持

2025年-2030年  国家重点研发计划青年科学家项目　主持

2025年-2029年  国家自然科学基金面上项目　主持

2025年-2026年  中央高校基本科研业务费专项资金项目　主持

2025年-2028年  湖北省自然科学基金创新群体项目　骨干

2023年-2026年  国家高层次人才计划青年项目　主持

ORCID: 0000-0002-5890-9204    (^#  = 共同一作,  * = 通讯作者)

Yu M.,^# Heidari M.,^# Palacio-Rodriguez, K., Ruan H., Mingu S., Hidayat A.A., Bode M., Sikora M., Hummer G.,* Lemke E.A.* O-GlcNAcylation and an importin-β radial gradient keep the FG barrier liquid in live-cell nuclear pores. BioRxiv, https://doi.org/10.64898/2025.12.09.693204, 2025

Chen Y.,^# Zhou G.,^# Yu M.,* Conformational dynamics of the nuclear pore complex central channel. Biochemical Society Transactions, 53, 1-14 2025.

Yu M.,^# Gruzinov A.,^# Ruan H.,^# Scheidt T.,^# Chowdhury A., Giofre A., Mohammed A., Caria J, Sauter P., Svergun D.,* Lemke E.A.* A genetically encoded anomalous SAXS ruler to probe the dimensions of intrinsically disordered proteins . PNAS 121(50), e2415220121, 2024.

Shammas S., Heller G., Bah A., Filippidi E., Holehouse A., Yu M., Lautenschläger J.  Ordering the disordered. Struture, 32 (9), 1288-1293, 2024

Yu M.,^# Heidari M.,^# Mikhaleva S.,^# Tan P.S.,^# Mingu   S., Ruan H., Reinkermeier C.D., Obarska-Kosinska A., Siggel M., Beck M., Hummer G.,* Lemke E.A.* Visualising the disordered nuclear transport machinery in situ. Nature 617, 62–169, 2023.

Scheidt T.,^# Ruan H.,^# Yu M.,^# Lemke E.A.* Stressing the role of a short linear motif in ataxin-2 condensation. Molecular Cell 83 (12), 1961-1963, 2023.

Yu M.,   Lemke E.A.* There is plenty of room in protein-RNA condensates. Biophysical Journal. 6, 120 (7):1121-1122, 2021.

Werther P., Yserentant K., Braun F., Grußmayer K., Navikas V., Yu M., Zhang Z., Ziegler M.J., Mayer C., Gralak A.J., Busch M., Chi W., Rominger F.,   Radenovic A., Liu X., Lemke E.A., Buckup T., Herten D.P.,* Wombacher R.*   Bio-orthogonal Red and Far-Red Fluorogenic Probes for Wash-Free Live-Cell and   Super-resolution Microscopy.  ACS   Central Science 7 (9), 1561-1571, 2021.

Heinss N.,^# Sushkin M.,^# Yu M., Lemke E.A.* Multifunctionality of F-rich Nucleoporins. Biochemical Society   Transactions 48 (6): 2603-2614, 2020.

Hou Y., Wang Y., Yu M., Wang Z.,* Yu H.* Miura-ori Metastructure Enhanced Conductive Elastomers. Advanced Materials Technologies 5 (8), 2000249,  2020.

Chowdhury A.,^# Yu M.,^# Lemke E.A.*   Phase Separation Comes of Age: From Phenomenology to Single Molecules. Molecular   Cell 74 (3), 413-415, 2019.

Li W.,^# Yu M.,^# Sun J.,^#   Mochizuki K., Chen S., Zheng H., Li J., Yao S., Wu H., Ong B., Kawata S.,   Wang Z.,* Ren K.* Crack Engineering for The Construction of Arbitrary Hierarchical Architectures. Proceedings of the National Academy of Sciences of the United States of America 16 (48), 23909–23914, 2019.

Hui T., Cho W., Fong H., Yu M., Kwan K., Ngan K., Wong   K., Tan Y., Yao S., Jiang H., Gu Z., and Lin Y.* An Electro-osmotic Microfluidic System to Characterize Cancer Cell Migration Under Confinement. Journal   of the Royal Society Interface 16 (155), 20190062, 2019.

Yu M.,^# Hou Y.,^# Song R., Xu X., Yao S.* Tunable Confinement for Bridging Single-cell Manipulation and Single-molecule DNA Linearization. Small   14, 1800229, 2018.

Hou Y., Shang Y., Yu M., Feng C., Yu H., Yao S.*  Tunable Water Harvesting Surfaces Consisting of Biphilic Nanoscale   Topography, ACS Nano 12 (11), 11022-1103, 2018

Song R., Peng C., Xu X., Wang J., Yu M., Hou Y., Zou R.,* Yao S.* Controllable Formation of Monodisperse Polymer Microbubbles as Ultrasound Contrast Agents, ACS Applied Materials & Interfaces 10 (17),   14312-14320, 2018.

Hou Y.,^# Yu M., ^# Shang Y., Zhou P., Song R., Xu X., Chen X., Wang Z., Yao S.* Suppressing Ice Nucleation of Supercooled Condensate with Biphilic Topography. Physical Review Letters 120 (7), 075902, 2018.

Shang Y., Hou Y., Yu M., Yao S.* Modeling and Optimization of Condensation Heat Transfer at Biphilic Interface.   International Journal of Heat and Mass Transfer 122, 117-127, 2018.

Xu X., Yuan H., Song R., Yu M., Chung C., Hou Y., Shang Y., Zhou H., Yao S.* High Aspect Ratio Induced Spontaneous Generation of Monodisperse Picolitre Droplets for Digital PCR, Biomicrofluidics 12 (1), 014103, 2018.

Chen Y., Huang L., Dai X., Tian Q., Yu M., Agheb M., Chan H., Poon E., Guo Z., Boheler K., Wu H.* Facile Formation of a Microporous Chitosan Hydrogel Based on Self-crosslinking, Journal of Materials Chemistry B 5   (47), 9291-9299, 2017

Xu X., Song R., He M., Peng C., Yu M., Hou Y., Qiu H., Zou R.,* Yao S.* Microfluidic Production of Nanoscale Perfluorocarbon Droplets as Liquid Contrast Agents for Ultrasound Imaging, Lab on a Chip 17 (20),   3504-3513, 2017.

Hui T., Kwan K., Yip T., Fong H.,   Ngan K., Yu M., Yao S., Ngan A.,* Lin Y.* Regulating the Membrane Transport Activity and Death of   Cells via Electroosmotic Manipulation, Biophysical Journal 110 (12),   2769-2778, 2016.

Hou Y., Yu M., Chen X., Wang Z.,* Yao S.* Filmwise-to-Dropwise Transition Enabled by Patterned High Wetting Contrast. Journal of Heat   Transfer, 137 (8), 080907, 2015.

Yu M., Hou Y., Zhou H., Yao S.* An On-demand Nanofluidic Concentrator. Lab on a Chip, 15 (6), 1524-1532, 2015.

Hou Y., Yu M., Chen X., Wang Z.,* Yao S.* Recurrent Filmwise and Dropwise Condensation on a Beetle Mimetic Surface. ACS Nano 9, 71-81, 2015. (Front cover article)