运用遗传编码的新型成像技术研究缝隙连接在疾病中的功能

Gap junctions are special intercellular channels that allow direct electrical coupling or exchange of small chemical molecules between adjacent cells. They play essential roles in synchronizing electrical activities within our cardiovascular and nervous systems, regulating embryonic development and tissue homeostasis. Mutations in genes encoding gap junction proteins may result in genetic disorders, such as familiar deafness, infertility, and abnormal development of central and peripheral nervous system. Traditionally, pair electrophysiological recordings and dye coupling assay are the main methods for detecting functional gap junctions. However, these methods are invasive, time-consuming and low-throughput. In this project, we aim at developing two novel methods, a genetically-encoded method and a hybrid chemical-biological method, for imaging the functional coupling of gap junctions. Combining with transgenic driver lines, our methods would allow imaging of gap junction coupling in a cell type-specific manner, hence providing new insights into their function in health and diseases.

缝隙连接是相邻细胞之间进行直接的电信号传递或小分子化合物交换所使用的一种特殊通道。这种通道在调节我们心血管及神经系统内电活动信号的同步性，胚胎发育及组织的平衡维持等方面都起着极为重要的作用。编码缝隙连接蛋白的基因突变会引起家族性耳聋、不育、中枢外周神经系统发育异常等多种遗传性疾病。传统的研究缝隙连接功能的方法主要包括电生理记录和化学染料成像等。这些方法对细胞的伤害大、实验耗时长且效率低。本项目旨在开发全遗传编码或与化学生物学相结合的新型成像技术，进而在疾病相关动物模型中运用此方法，来阐述缝隙连接突变相关的致病机理。

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