环境污染物暴露的DNA和组蛋白表观遗传标志物的纳米孔道单分子研究

环境污染物暴露诱导表观遗传失调会驱动异常的转录程序，促进肿瘤等多种疾病的发生和进展。精准测量环境污染物暴露的表观遗传标志物对于准确理解环境与基因组互作在疾病发生中的作用机制具有重要意义，已成为环境化学和生命分析科学领域的研究热点。DNA甲基化和组蛋白修饰是环境致癌物早期接触暴露的表观遗传标志物，常用分析方法通常获取大量分子的整体平均性质，难以准确识别分子个体的表观遗传差异。因此，针对环境污染物暴露的DNA和组蛋白表观遗传标志物精准测量这一研究需求，本项目拟设计构建多个灵敏位点协作的Aerolysin生物纳米孔道单分子测量体系，获取大量具有明显阻断和频率特征的单分子时序离子电流信号；进一步，开发纳米孔道单分子数据智能分析算法，精准解析DNA和组蛋白表观遗传修饰类型与程度，建立准确识别多种表观遗传标志物的纳米孔道单分子研究方法，为阐明环境污染对健康损害的表观遗传作用分子机制提供新线索。

Epigenetic dysregulation induced by environmental pollutant exposures can drive abnormal transcription of genes, promoting the occurrence and progression of tumors and other related diseases. Accurate measurement of the epigenetic markers of environmental pollution exposure has become the research frontier in the fields of environmental chemistry and life science, which is of great significance for precisely understanding the interaction mechanism of environment and genome in the occurrence of diseases. DNA methylation and histone modification are new biomarkers for early exposure of environmental carcinogens. Traditional analysis methods usually obtain the ensemble properties of a large number of molecules, and has difficulty in accurately identifying the epigenetic differences of individual DNA and histone molecules. Therefore, in order to achieve single-molecule precise measurement of epigenetic markers of environmental pollutant exposures, this project plans to design and construct aerolysin nanopore interfaces with multiple sensing sites to obtain ionic current signals of single molecules with obvious blocking and frequency characteristics. Furthermore, an intelligent analysis algorithm will be developed to accurately analyze nanopore data to determine the type and degree of DNA and histone epigenetic modifications. A nanopore-based single-molecule method will be established for precise identification of multiple epigenetic modifications, providing new insights into understanding molecular mechanism of the epigenetic effect of environmental pollution on health damage.