蛋白质折叠和质量控制的分子机制是生物学中最为重要的问题之一。但是，我们对于细胞内不同的因子是如何协同调控并完成有效的蛋白质折叠的机理还知之甚少。建立在前期的研究工作基础之上，本项目设计了一个基于内质网蛋白质折叠的筛选策略来全面且定量的寻找出影响内质网蛋白质折叠的因子。前期的实验已鉴定出包括分子伴侣在内的影响内质网蛋白质折叠的因子，从而验证了这一方法的可行性。本项目将全面揭示影响内质网蛋白质折叠的调控网络，并深入研究未知功能的因子所扮演的角色。这些新的发现不仅会推进我们对于蛋白质折叠的分子机制的了解，也会创造出有用的工具为合成生物学服务，从而实现直接将理论研究的成果转化为应用。

Protein folding and quality control is one of the most fundamental questions in biological research. However, little is known about how different factors inside the cell are regulated in a coordinated manner to support efficient cellular protein folding. Here, building up our previous findings, we take advantage of a recently developed folding substrate that allows us to search for factors that are required for endoplasmic reticulum (ER) protein folding in a quantitative and unbiased manner. The preliminary experiments have already identified factors with known function in ER protein folding (including chaperones), which provided the proof of principle for this strategy. This proposed project aims to reveal the network, composed of various direct and indirect factors, that regulates ER protein folding. Novel folding factors that have not been characterized will be studied in detail. These new findings will not only advance our understanding of the molecular mechanism of protein folding, but will also generate useful tools that can be widely used in synthetic biology. By doing this, we will directly translate the outcome of basic research into potential commercial applications.