端粒酶是在细胞中负责端粒延长的逆转录酶, 包括逆转录酶催化亚基TERT和RNA模板亚基TERC两个重要组分。本研究拟运用增强的逆转录病毒诱变子技术（ERM）和双分子荧光互补技术（BiFC）相结合的高通量筛选蛋白-蛋白互作的平台，以及以MS2-TriFC为基础的高通量筛选蛋白-RNA互作的平台,筛选与TERT、 TERC相互作用的蛋白质并绘制端粒酶互作蛋白精细网络图谱，从而系统地发现与端粒酶互作的蛋白质复合物及调控端粒酶的不同信号通路，以及这些通路与端粒维持之间的关系。通过本课题进一步完善以ERM-BiFC和MS2-TriFC为基础的高通量筛选蛋白-蛋白和蛋白-RNA相互作用的技术平台，并深入研究新的TERT和TERC结合蛋白在端粒酶活性调控和端粒维持上的功能。这将极大地推进对端粒酶活性调控、端粒维持和肿瘤发生的分子机制的理解，而且为解决衰老性疾病和肿瘤治疗提供新的思路。

Telomeres are specialized DNA–protein structures at the ends of eukaryotic chromosomes. The primary function of telomeres is to protect chromosome ends against fusion，abnormal recombination and degradation. The protein complex responsible for synthesis of telomeres in the cells is telomerase, which has two important components including the reverse transcriptase catalytic subunit TERT and RNA template subunit TERC. We will apply technology with the combination of Enhanced retroviral mutagen technology (ERM), Bimolecular fluorescence complementation technology (BiFC) and MS2- Trimolecular fluorescence complementation technology (TriFC) to do high throughput screening of TERT interacting protein and TERC binding protein, thus systematically identify telomerase associated protein and regulators of telomerase in different signaling pathways, and explore the relationship between these pathways and telomere maintenance. Our study will not only greatly promote the understanding of the telomerase regulation，telomere maintenance and the molecular mechanisms of the tumorigenesis, but also provide new insight on age-related diseases including cancer.