核纤层蛋白附着在细胞核膜内表面形成一层薄薄的纤维网络状结构，核纤层及其相关蛋白突变会引起很多遗传疾病如早衰病和脱髓鞘脑白质退化症等，核纤层蛋白分子功能研究具有重要临床诊断和治疗价值。前期我们通过改造CRISPR/Cas9在单细胞内标记非重复和低重复染色体区域，开发了活细胞追踪特异染色体区域动态、功能的方法。本研究基于前期开发CRISPR/Cas9方法标记活细胞中特异核纤层关联区（LAD），免疫沉淀特异核纤层LAD内RNA、蛋白质分子并高通量分析鉴定；结合核纤层蛋白生长素诱导降解系统，通过活细胞成像研究核纤层蛋白表达和缺失情况下染色体结构、动态变化；通过组学方法检测核纤层蛋白表达和缺失情况下RNA和蛋白表达差异。本研究利用交叉学科多方法阐释核纤层蛋白表达和缺失情况下细胞染色体结构、基因表达变化，揭示核纤层蛋白分子功能及突变缺失导致遗传病的分子机理，为疾病诊断和治疗提供理论基础。

Nuclear lamins form a thin layer of fibrillary network residing on the inner nuclear membrane. The mutation of lamin or lamin associated proteins lead to multiple genetic diseases including Hutchinson-Gilford Progeria Syndrome, Demyelination of the white matter of the brain, et al. Thus, the functional study of lamin proteins is crutial for clinical diagnosis and treatment. Previously, we have engineered the CRISPR/Cas9 system to achieve the efficient labeling of low- and non-repetitive chromosome loci and track the dynamics of chromosome targets. Lamin binding factors including RNA and protein are characterized by immunoprecipitation and high-throughput analysis. In order to compare the chromosome architecture, gene transcription, and protein expression with and without lamin proteins, we propose to utilize CRISPR/Cas9 to label lamin associatd domains and control the level of endogenous lamin proteins using auxin-induced degron strategy. This study will identify the nuclear perturbation, gene transcription, and protein expression induced by lamin depletion from structure and dynamics perspective, lay the foundation for future diagnosis and treatment of human diseases caused by lamin mutations.