细胞器组分/微环境辅助亚细胞限域荧光放大新方法研究

发展准确高效的细胞器内生化信息获取技术是探究亚细胞水平上生命机制和理解细胞器功能本质的关键所在，也是目前化学测量学与生命分析化学研究热点之一。本项目应对细胞器内生命活动或疾病密切相关低丰度物质难于原位成像分析的挑战，突破传统细胞器靶向荧光探针设计思维定势和原有信号放大方法局限性，开展亚细胞层面生化信息原位实时获取新原理和新方法研究：提出利用细胞器自身属性，借助于细胞器内固有组分或局部微环境，发展兼具信号放大和信号限域特征的荧光传感新机制，系统创建亚细胞区域定位超灵敏高分辨荧光成像新体系，并应用于细胞内信号转导通路和细胞器功能障碍等生理病理现象的分子作用原理研究。本项目的执行将为丰富与发展高效细胞器靶向荧光成像探针提供新思路，推动信号放大策略在亚细胞分析的拓展与应用，为阐明亚细胞水平生物活性物质变化与生命活动规律或疾病成因之间关系提供新工具和新方法。

Development of accurate and efficient technique for acquiring biochemical information in organelles is key to exploring the mechanisms of life under subcellular level and understanding the essence of organelle functions, and is also one of research hotspot in chemical measurement science and analytical chemistry for life science. To address the challenge of in situ detection of low abundance bioactive substances relative to living activity and disease, focusing on breaking through the design paradigm of conventional organelle-targetable fluorescent probes and limitation of signal amplification methods, this project will study the novel method and principle of in situ and real-time biochemical information acquisition under subcellular level: it is proposed to employ own properties of organelles to realize organelle constituent/microenvironment assisted fluorescence amplification under subcellular define region, thus creating subcellular location sensing and imaging system with ultra-sensitivity and high-resolution, which hold the potential to be applied in researches on the molecular mechanisms of cell signal transduction pathway, organelle dysfunction and other physiological or pathological phenomenons. The execution of the project would provide new thought to enrich the types of organelle-targetable fluorescence probe, propel the signal amplification strategy into subcellular analysis, and give new tool and new method for exploring the relation between the biological active species with life activities and diseases in subcellular level.