西湖大学张鑫团队在研究中取得进展。他们揭示了时间分辨荧光蛋白扩展荧光显微镜在时间和光谱领域。相关论文于2025年9月22日发表于国际顶尖学术期刊《细胞》杂志上。

在这里，课题组研究人员提出了一个家族的时间分辨荧光蛋白（tr-FPs）具有合理控制寿命。使用一种不影响FPs光谱的调节寿命策略，课题组研究人员开发了一系列覆盖可见光谱和广泛寿命范围的tr-FPs。tr-FPs用于时间光谱分辨显微镜，允许同时成像活细胞中的9种不同蛋白质以及多种活性与细胞周期的相关性。

此外，tr-FPs支持多路超分辨率显微镜，可以同时显示4种蛋白质的生命周期信号，并被证明可以量化细胞蛋白质的化学计量学。他们的工作介绍了tr-FPs作为一种变革性工具集的概念和发展，为将系统复杂性和定量准确性集成到生物学研究中提供了机会。

据介绍，荧光显微镜在生命科学中有着广泛的应用。虽然强度作为稳态信号被广泛关注，但时间分辨（tr）信号主题荧光寿命仍未得到充分探讨。

附：英文原文

Title: Time-resolved fluorescent proteins expand fluorescent microscopy in temporal and spectral domains

Author: Zizhu Tan, Chia-Heng Hsiung, Jiahui Feng, Yangye Zhang, Yihan Wan, Junlin Chen, Ke Sun, Peilong Lu, Jianyang Zang, Wenxing Yang, Ya Gao, Jiabin Yin, Tong Zhu, Yang Lu, Zijian Pan, Yilong Zou, Can Liao, Xiaosong Li, Yuxuan Ye, Yu Liu, Xin Zhang

Issue&Volume: 2025-09-22

Abstract: Fluorescence microscopy has been widely applied in the life sciences. While intensity as a steady-state signal is widely used, the time-resolved (tr) signal using fluorescence lifetime remains underexplored. Herein, we present a family of time-resolved fluorescent proteins (tr-FPs) with rationally controlled lifetimes. Using a strategy that regulates lifetime without affecting the spectra of FPs, we have developed a series of tr-FPs that cover the visible spectrum and a wide range of lifetimes. The tr-FPs are employed in temporal-spectral resolved microscopy, allowing for the simultaneous imaging of 9 different proteins in live cells and the correlation of multiple activities to cell cycles. Furthermore, tr-FPs enable multiplexing super-resolution microscopy that concurrently visualizes 4 proteins using the lifetime signal and are demonstrated to quantify the stoichiometry of cellular proteins. Our work introduces the concept and development of tr-FPs as a transformative toolset, presenting opportunities to integrate system complexity and quantitative accuracy into biological research.

DOI: 10.1016/j.cell.2025.08.035

Source: https://www.cell.com/cell/abstract/S0092-8674(25)01027-X