核糖体是由RNA和蛋白质组成的一个超大型复合物，负责细胞内所有蛋白质的合成。细菌的核糖体和蛋白质合成一直是抗生素的最主要靶点，因此对核糖体靶向抗生素的结构和生化研究对理解抗生素的工作机理和耐药性机制至关重要。本项目中我们将以Tetracycline（四环素）和Dityromycin两种抗生素为研究对象，利用核糖体高分辨率晶体学结合体外翻译系统，对四环素的耐药性机制之一和Dityromycin的抑制核糖体活性机制展开深入的研究，为Tetracycline的改进和Dityromycin的临床转化做出必要铺垫。

Protein synthesis occurs on the ribosome, a gigantic cellular complex comprised of RNA and proteins. Bacterial ribosomes and the process of protein synthesis are the major targets of antibiotics. Therefore, structural and biochemical studies of ribosome-targeting antibiotics can provide valuable mechanistic insights into the modes of action of antibiotics and their associated drug resistance. This project focuses on the investigations of the antibiotic Tetracycline and Dityromycin. Using high-resolution ribosome crystallography in combination with cell-free in vitro translation system, we shall study the molecular mechanism of tetracycline resistance provided by protein projection proteins and the working mechanism of the newly characterized Dityromycin.