超高时空分辨蛋白质机器动态成像

Extra High Spatio-Temporal Resolution Imaging of Protein Machine

蛋白质是生命活动的主要执行者,一切生命活动都有赖于蛋白质功能的正确发挥。蛋白质机器,是指由大量蛋白质和生物分子形成的高维度的、复杂的超级功能复合体,此外也包括蛋白质与蛋白质或其他分子形成的低维度复合物及具有特定生物学功能的蛋白质分子。膜转运和跨膜信号转导是细胞的重要生命活动过程,与细胞命运和功能密切相关。细胞中蛋白质机器是高度动态的,由于组成复杂、功能多样,在分子水平研究蛋白质机器行为机制对成像技术提出了极大的挑战,针对重大生命过程中蛋白质机器动态组装与功能调控的分子机制这一核心科学问题,提出了解决这些难题的工作思路和重点研究内容。从提高成像时空分辨率、实现时空可控和多模态融合入手,发展多种新型成像和关联技术,揭示膜转运和跨膜信号转导等重要生命过程中蛋白质机器的作用机制。提出的主要研究内容包括下一代超高时空分辨结构光照明显微镜、超分辨荧光成像技术和原子力显微镜联用、时间相关的超分辨显微镜与冷冻电镜关联技术。

Proteins are the direct performer of life activity, while they are responsible for carrying through the functions of biological events. Protein machine is defined as the large and high-dimension complex of protein and biological molecules, moreover also including the low dimension compounds formed with proteins or other molecules, and single protein molecules with specific biological functions. The protein machine in the cell is highly dynamic. Membrane transport and transmembrane signal transduction are important processes of cellular activity, which are closely related to cell fate and function. Because of the diversity and complication of the protein machine, studying the mechanism of protein machinery at the molecular level poses a great challenge to imaging technology. Focusing on the molecular mechanism of dynamic assembly and function regulation of protein machine in life process, we propose advanced technical strategy and research methods. We will improve the spatial and temporal resolution of imaging, realize the integration of spatio-temporal control and mul- timodal state, and develop various new imaging and related technologies; eventually, we will reveal the mechanism of membrane transport and transmembrane signal transduction by these techniques. This project includes the R＆D of the next-generation high spatio-temporal resolution structured illumination microscopy （SIM）, the combination of atomic force microscopy and super- resolution fluorescence imaging, and the time-correlation super-resolution fluorescence microscopy/cryo-electron microscopy, with the aim of solving biological problems.