天然免疫及其相关的细胞信号转导研究 天然免疫系统是多细胞生物抵抗病原微生物感染的第一道防线。天然免疫受体通过识别病原体和内源有害分子所特有的分子特征,激活细胞内的一系列信号转导通路,继而引起特异性细胞因子的表达,快速发挥免疫防御作用。同时,天然免疫反应还可以进一步激活获得性免疫反应。天然免疫应答与机体抗病原感染的能力,自身免疫病的发生,过敏性疾病及炎症引起的癌症等密切相关。
本实验室利用多种技术:大规模、高通量克隆表达及功能筛选、规模化酵母双杂交和蛋白质分离-肽谱技术,对调控天然免疫的相关蛋白进行大规模、高通量筛选、克隆及功能研究,寻找并发现天然免疫中调控不同细胞信号通路的新基因及已知基因在天然免疫中的新功能;利用免疫学、细胞生物学、分子生物学、生物化学、遗传学、结构生物学等技术来研究这些基因的功能及作用机制,深入而系统地研究天然免疫反应的分子机制,为相关疾病的预防和治疗提供理论依据。
关键科学问题 我们围绕细胞受到病原微生物感染后天然免疫激活,并最终产生、分泌细胞因子这一重要生理过程,通过新基因、新通路的发现与机制研究,探讨细胞进行天然免疫反应的分子机制,揭示天然免疫应答失控导致各种与感染免疫相关的疾病,包括过敏性反应、自身免疫病、慢性炎症(及导致肿瘤发生)的可能原因。
1) 细胞识别病原微生物,激活天然免疫的分子机制;
2) 泛素化参与抗病毒信号通路的机制;
3) 天然免疫活化引发I型干扰素及其它重要细胞因子产生与调控的分子机制;
4) 天然免疫活化后细胞因子分泌的机制;
5) 天然免疫关键信号分子的调节和多种疾病(过敏反应、自身免疫病及慢性炎症)的相互关系;
6) 重要信号分子的结构及功能。
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