申请人长期研究离子通道功能异常在自闭症发病机制中的作用。主要学术成绩包括：1）首次发现自闭症的产生与L-型钙通道异常的构象信号相关，揭示了自闭症发生的新机制—构象信号异常；成果以共同第一作者（排名第一）发表于Science。2）首次发现与自闭症相关的BK 通道存在于神经元细胞核膜，揭示了自闭症发病的新机制—核膜机制；成果以第一作者发表于Nat Neurosci。3）发现与自闭症相关的KATP通道的新功能—调控线粒体ROS释放及ERK激活；成果发表于Carcinogenesis和Mol Neurobiol。主持国家自然科学基金2项，广东省杰出青年基金1项，获FASEB会议奖学金及最佳论文奖。本项目中，申报人将创立光控蛋白降解技术和光控特异性激活技术，并以此阐明细胞不同部位L-型钙通道功能改变对基因表达的调控及其在自闭症中的作用，提出自闭症新的发病机制；为其它离子通道研究提供新的研究手段。

The applicant has been working on the roles of ion channel dysfunction in the etiology of autism for years. The main achievements include: 1) establish the relationship between autism and abnormal conformational signal of L-type calcium channels, reveal the new mechanism of autism---abnormal conformational signal. The findings have been published in Science as first co-first author. 2) Discover the existence of autism-related ion channel (BK channel) on the nuclear envelope, reveal the new mechanism of autism---nuclear envelope mechanism. The findings have been published in Nature Neuroscience. 3) Find the new function of the autism-related KATP channel--regulating ROS release and ERK activation. The findings have been published in Carcinogenesis and Molecular Neurobiology. As principle investigator, the applicant has been funded by two grants from NSFC, one grant for Distinguished Young Scholar from Guangdong Natural Science Foundation, and has been awarded with scholarship and best presentation award from FASEB. In the current application, the applicant will develop new techniques of "opto-protein degradation" and "opto-activation", and try to reveal the different roles of subcellular L-type calcium channels in the regulation of gene expression and etiology of autism. This study will help provide new molecular mechanisms and new therapeutic strategies for autism. Meanwhile, the new methods in the current study will provide new tools for functional studies of other ion channels.