Trigger factor(TF)是原核分子伴侣系统中的重要成员，具有帮助蛋白折叠、调控核糖体组装等众种重要的生理功能。TF的多功能性源自于其所具有的独特龙形分子结构，人们认为TF表面上存在有多个功能位点，这些位点能够以多种方式与众多生物分子发生相互作用，从而赋予TF多样的生理功能。然而除了核糖体结合位点和PPIase位点外，TF的其他功能位点尚未被鉴定出来。因此TF的生理功能及其作用机制目前尚不清楚。本课题拟运用包括转录组学、蛋白组学、表型组学等多种高通量手段致力于TF功能位点的鉴定、TF生理通路的建立等工作；并通过等温量热滴定、电镜等多种分子结构和相互作用研究技术，阐明TF表面上的功能位点与TF通路成员之间的互动关系，从而在残基甚至在原子水平上揭示TF生理功能的作用机制。这些研究将能够提高人们对TF、以及分子伴侣系统运行机制的的认识，有助于对大肠杆菌进行改造，提高外源蛋白表达效率。

Trigger factor (TF) is a key component of prokaryotic chaperone network, and plays important roles in many diverse physiological processes, such as nascent chain folding, ribosome assembly and so on. The multifunctionality of TF arises from its unique dragon-shape modular structure containing many patches with different physical and chemical properties on the surface. These patches are regarded as potential functional sites and expected to interact with many proteins or other molecules in cytosol in various manners, enabling TF to be involved in many physiological processes. However, most functional sites of TF, except ribosome binding site and peptidyl prolyl cis-trans isomerase (PPIase) site, are not identified yet, resulting in that the physiological roles of TF and the underlying mechanisms remain unclear. In this project, we will engage in systematically identifying functional sites of TF and dissecting the physiological pathways mediated by TF using omics tools such as transcriptomics, proteomics and phenomoics. Thereafter, we will use isothermal titration calorimetry (ITC), Cryo-EM and other spectroscopic techniques to investigate the interaction between functional sites of TF and the components of TF physiological pathways, in order to elucidate the molecular mechanism underlying physiological function of TF at the level of residue or even atom. Our research will increase our understanding of TF and prokaryotic chaperone network, contributing to reprogramming physiological pathways of E.coli for improving the production of recombinant proteins.