研究方向
运用低温冷冻电镜、病毒学、细胞生物学等技术方法,从事人类重大疾病直接相关的病毒完整颗粒及病毒与受体、病毒与抗体的超大分子复合物的精细三维结构和相关功能研究,揭示病毒入侵宿主细胞的分子机制和致病机理以及抗病毒药物研究。主要研究方向包括:1. 疱疹病毒的复制、组装和运输机制;2. 脑炎性黄病毒神经毒力的分子机制;3.小RNA病毒的入侵和组装机制及抗病毒药物研究。
1. 疱疹病毒的复制、组装和运输机制
疱疹病毒是在世界范围内广泛传播的一大类病毒,包含病毒的种类众多,能够感染包括人类在内的多种哺乳动物。疱疹病毒在感染人体后能够引发多种疾病,包括口腔和生殖器疱疹、水痘、带状疱疹,严重的甚至包括多种免疫系统疾病、脑炎以及癌症等。疱疹病毒有着独特的潜伏-再活化机制,疱疹病毒可以关闭其大部分活动状态的基因,只在特定的潜伏阶段打开特定的少数基因,并在合适的条件下恢复活性,重新进入增殖过程。这种潜伏-再活化机制使得疱疹病毒感染产生的疾病难以完全治愈,通常患者会终生携带病毒。同时疱疹病毒又是非常好的“融瘤”和“神经环路示踪”工具,目前已经进入临床应用。本课题组致力于理解疱疹病毒的复制、组装的动态过程,揭示疱疹病毒在宿主细胞的运输和潜伏与再激活分子机理,为有效防治疱疹病毒的感染和人类生命医学技术手段的提高提供理论基础。
2. 脑炎性黄病毒神经毒力的分子机制
黄病毒,是一类具有包膜的单股正链RNA病毒,主要是通过吸血的节肢动物(蚊、蜱、白蛉等) 进行传播的虫媒病毒,能够广泛引起人类很多重大传染性疾病,主要包括乙型脑炎病毒 (JEV)、森林脑炎病毒、登革热病毒、寨卡病毒和黄热病毒等。黄病毒科中有一大类病毒能够直接入侵脑部而引起的颅内急性炎症,即:病毒性脑炎。本课题组聚焦脑炎性黄病毒神经毒力的分子机制。
3. 小RNA病毒的入侵和组装机制及抗病毒药物研究
小RNA病毒是一类无包膜的单股正链RNA病毒,可引起人类和动物多种严重疾病,如:甲型肝炎、小儿麻痹症、口蹄疫、手足口病和普通感冒等。除了是众多疾病的主要病原,小RNA病毒也是研究病原(病毒)与宿主之间的关系、病毒的入侵和病毒基因组的释放等关键科学问题最好的模型之一。本课题组致力于揭示小RNA病毒入侵宿主细胞和病毒发生脱衣壳过程的动态分子机制,在此基础上靶向设计能够高效阻止病毒入侵过程的小分子抑制剂及稳定性高、免疫原性好的病毒样颗粒候选疫苗。
代表性论文( * Corresponding Authors, # First Authors ):
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