邀请人：朱洪涛 特聘研究员（hongtao.zhu@iphy.ac.cn）

报告摘要：
Type A GABA receptors (GABAARs) are pentameric ligand-gated ion channels that mediate the principal fast inhibitory signaling in the mammalian brain and are essential for maintaining the balance between excitation and inhibition. Dysfunction of GABAARs has been implicated in a wide range of neurological and neuropsychiatric disorders, including anxiety, epilepsy, autism spectrum disorders, schizophrenia, and Alzheimer’s disease. Despite their importance as drug targets, precise pharmacological modulation of GABAARs remains difficult because the molecular identities and distributions of native receptor populations in the brain are still incompletely understood.

Using native purification approaches together with single-molecule and structural methods, I have characterized α1-containing GABAAR populations from the mammalian brain1,2 and begun to define their molecular composition and pharmacological diversity. In this seminar, I will discuss the experimental challenges of studying endogenous GABAARs, the strategies we have developed to overcome them, and how these advances open new opportunities for understanding subtype-specific receptor function and for guiding the development of more precise neuroactive therapeutics.

1  Sun, C., Zhu, H., Clark, S. & Gouaux, E. Cryo-EM structures reveal native GABAA receptor assemblies and pharmacology. Nature 622, 195–201 (2023). https://doi.org/10.1038/s41586-023-06556-w

2  Sun, C., Jahncke, J. N., Wright, K. M. & Gouaux, E. Molecular assemblies and pharmacology of cerebellar GABAA receptors. Proceedings of the National Academy of Sciences 123, e2524504123 (2026). https://doi.org/doi:10.1073/pnas.2524504123

报告人简介：
孙畅博士，现任范安德尔研究所研究科学家，2025年入选人才计划，即将全职加入武汉大学药学院任教。孙博士本科毕业于复旦大学药学院，随后于美国伊利诺伊大学厄巴纳-香槟分校获生物化学博士学位，并先后在贝克曼研究所与俄勒冈健康与科学大学从事结构生物学研究。他长期致力于从原子分辨率层面阐明膜蛋白（特别是电子传递链复合物与离子通道）的结构与功能机制。其研究手段涵盖了从利用电子顺磁共振技术原位探测泛醌自由基在蛋白结合口袋中的微环境，到运用冷冻电镜技术解析膜蛋白的三维全局结构。在复杂膜蛋白样品的生化制备与高分辨率结构解析领域，孙博士积累了深厚的研究造诣。

在方法学创新方面，孙博士率先将两亲性共聚高分子引入冷冻电镜的膜蛋白研究中，并依托该前沿技术成功解析了替代性复合物三的亚基空间排布与电子传递网络。此外，他利用重组抗体技术成功从脑组织中纯化出关键的神经受体（γ-氨基丁酸受体），并通过冷冻电镜系统阐明了其复杂的组装模式与药理学机制。相关核心成果已在 Nature、PNAS、J. Am. Chem. Soc.、Biochemistry 等国际顶级与权威学术期刊发表论文10余篇，其中以第一作者身份在 Nature 发表论文2篇。作为项目的核心骨干，孙畅博士在离子通道的分子机理探讨与冷冻电镜前沿技术应用方面具备极强的科研实力，曾多次受邀在离子通道戈登研究会议、生物物理年会等顶尖国际学术会议，以及美国西北大学、普渡大学等知名高校作特邀学术报告。