1. DNA 表观遗传修饰对生命活动的影响(Impact of DNA phosphorothioate modification on bacterial and archaeal physiology)
作为一种新型的DNA表观遗传现象——DNA磷硫酰化修饰于2007年被鉴定,被《环球科学》评为当年“十大科学新闻”。不同于常见的甲基化、羟甲基化等碱基修饰,磷硫酰化修饰发生在DNA骨架上,即细菌和古菌能够利用DndABCDE 5 个蛋白对DNA磷酸二酯键中的非桥连氧原子进行硫取代,形成序列特异性、空间构象专一性的磷硫酰化结构。磷硫酰化生理修饰具有动态修饰特征,在原核生物和环境微生物组中广泛分布,并进化出多样的生理功能,包括参与限制-修饰防御、基因的表达调控、参与维持细胞内氧化-还原动态平衡等,可以与细胞中其它的防御系统组成防御网络。
2. 表观遗传修饰的生物医学应用(Epigenetic and biomedical applications)
表观修饰拓展了DNA的遗传信息,在细胞生命活动中起到了不可或缺的关键作用。我们致力于研究包含DNA磷硫酰化和甲基化在内的多种表观修饰对病原菌的致病性、细胞的生理及代谢的影响、以及相关的生物医学领域应用。由于抗生素的滥用,超级耐药菌的出现是现代医学面临的一个重大挑战。研究表观遗传修饰对耐药菌耐药机制所产生的影响,以及发展相应的小分子药物,并结合噬菌体疗法,解析噬菌体防治超级耐药菌的机制,为超级耐药菌的防治提供理论和应用基础。
3. 抵抗噬菌体污染的合成生物学底盘(Anti-phage bacterial chassis)
鉴定细菌限制-修饰系统多样性基因组成和抗噬菌体作用机制。联合细菌多种限制-修饰系统,组合不同抗噬菌体元件,构建具有多重噬菌体抗性的合成生物学底盘细胞,发挥其在工业发酵抗噬菌体污染中的应用。
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