谷氨酰胺（Glutamine，Gln）作为快速生长的哺乳动物细胞尤其是癌细胞的“必需品”，参与了多种多样的代谢活动。许多癌细胞更是表现出“谷氨酰胺成瘾”的特性，大量消耗Gln，在缺乏外源性Gln时不能存活。然而，针对Gln代谢，目前尚没有十分有效的原位检测方法，长期以来研究者主要依赖细胞裂解、色谱分析等传统生化方法检测Gln存在重大技术缺陷。近来我们针对细胞内核心代谢物NADH开发了一系列遗传编码的NADH荧光探针，实现了细胞代谢过程的可视化。本项目，我们将通过分子结构的理性设计和蛋白质工程，集中发展遗传编码的Gln荧光探针，实现在活细胞、各种亚细胞结构甚至活体组织中对Gln代谢的实时动态、特异性的定量检测与成像，并应用于高通量筛选，搜寻靶向肿瘤谷氨酰胺代谢的抗癌化合物。本研究将为生物医学研究提供创新性的工具和技术支撑，具有重要的科学意义。

Glutamine (Gln) participates in multiple metabolic processes as a necessity in fast-growing mammalian cells, especially cancer cells. Most cancers avidly consume glutamine, and many cancer cell lines are ‘addicted’ to this amino acid, as they cannot survive without an exogenous supply. However, there are few accepted methods to detect glutamine in situ. For many years, researchers have relied on conventional biochemical methods, such as cell lysis and chromatographic analysis, which have significantly technical deficiency. Recently, we have developed a series of genetically encoded fluorescent sensors for NADH, a key player in cell metabolism, realizing visualization of metabolic processes. In the project, we will develop genetically encoded Gln sensors by rational design of molecular structure and protein engineering. These sensors will be very helpful for the real-time detection and imaging of Gln in living cells, subcellular organelles and in vivo, and compatible with high-throughput screening for anti-tumor drugs. The project will provide novel tools for biomedical research.