修饰核酸的化学标记和检测技术研发

修饰核酸在生物体内发挥的功能，以及与基因调控和各种疾病有密切关系是表观遗传学研究的重要内容。很多核酸修饰是动态变化的，只有知道了修饰核酸在体内的分布，在基因组中的位置以及在不同状态或者不同细胞中的含量和分布，我们才能了解它们的功能。因此，开发对修饰核酸在基因组的分布、位点以及相关的功能的检测技术和策略，才能够了解它们与疾病和生命过程的关系。本项目中，我们将利用对修饰核酸能特异识别和共价结合的新型分子探针，针对在全基因组和短片断基因中5-醛基胞嘧啶、5-羧基胞嘧啶、5-醛基尿嘧啶、5-甲基胞嘧啶和N-6甲基腺嘌呤等修饰的识别、标记，通过对基因组中这些修饰核酸的反应、富集、高通量测序、生物信息学分析，完成部分修饰核酸的基因图谱（单碱基分辨率）的绘制，研发出能对这些修饰核酸检测的新策略、新技术和新方法，探讨修饰核酸在生物医学功能中的重要作用。

The important contents for epigenetic studies are that modified nucleic acids play important roles in biological functions, gene regulation and relation with many diseases. It is important to understand the mapping, sites and functions of modified nucleic acids in genome and therefore we could understand their relations to disease and life process. In this project, we shall design and synthesize the probes to specifically recognize and label to 5-methylcytosine, 5-formylcytosine, 5-hydromethylcytosine, 5-carboxylcytosine, 5-formyluracil and N-6 methyladenine respectively. Then, modified nucleic acids are enriched, high-throughput sequencing and finally bioinformatic analysis. Then we shall finish the mapping of modified nucleic acids in genome. We hope that we can get more new strategies, methods and techniques to map and detect the modified nucleic acids in genome. Using these new strategies, methods and techniques, we can get more important functional information of modified nucleic acids related to biomedical function.