针对信号转导过程研究的分析新方法与新技术

The project mainly focuses on the development of effective methods to understand the process involved in the signal transduction. To accomplish such a purpose, we will develop new principles and new methods that can be used for probing the signal transduction process at different levels ranging from single molecules, single cells, to in vivo. At the single molecular level, main of our efforts will be made on methodological development for in situ and real-time monitoring of molecular events occurring in the involved in signal transduction processes. Meanwhile, we will use microfluidic chip technology to develop the cell co-culture and further study the interactions between cells. By doing so, we may develop novel and effective protocols to understand the potential pathways involved in the signal transduction at a level of single cells. As another part of this project, we will be engaged in the establishment of new mechanisms and techniques that can be capable of in vivo continuous monitoring of physiologically important species such as neurotransmitters and neuromodulators to provide useful information to probe the chemical essence in the signal transduction. As the last but equally important part, we will try to use the methods developed in this project to understand the possible pathways of the signal transduction during the process of vertigo. This project is believed to be able to greatly facilitate the development of signal transduction research.

多层次、高效、准确获取信号转导分子的变化及相互作用的信息，是阐明信号转导机制的关键和基础。本项目拟从分子、细胞和活体三个层次入手，开展适合于信号转导过程的分析新原理和新方法的研究。在分子水平，拟发展对信号转导通路蛋白和离子等进行原位、实时、动态表征及相互作用研究的新方法，发展对信号通路蛋白的活细胞体系三维示踪和高空间分辨单分子成像新技术，为阐明信号转导及化学小分子探针干预信号的分子机制提供新的研究手段；在细胞水平，拟利用微流控芯片技术实现神经细胞与垂体细胞的共培养、药物刺激、代谢物富集和在线质谱检测，观察共培养过程中细胞间相互的诱导作用；在活体水平，拟结合纳米材料的最新进展，发展信号转导分子的实时在线分析新原理和方法；利用所建立的方法，探索耳鸣形成过程中可能的分子机制。本项目的实施将大大促进信号转导过程的研究，为认识生命过程的本质奠定基础。

多层次、高效、准确获取信号转导分子的变化及相互作用的信息，是阐明信号转导机制的关键和基础。本项目从分子、细胞和活体三个层次入手，开展了适合于信号转导过程的分析新原理和新方法的研究。在分子、细胞和活体水平，建立了多种生理活性分子的检测方法，并利用所建立的方法探索了耳鸣形成过程中可能的分子机制。本项目的实施过程中共发表重要代表论文21篇，包括J. Am. Chem. Soc. 1篇，Angew. Chem. Int. Ed. 1篇，Chem. Soc. Rev. 2篇。