氧化型烟酰胺腺嘌呤二核苷酸磷酸（NADP+）是广泛存在于生命体的一种重要的辅酶。其在氧化还原稳态维持中处于核心地位，并且参与磷酸戊糖途径、脂肪酸合成、解毒反应等多种代谢过程。此外，在癌症、糖尿病、神经系统病变等病理过程中，NADP+也扮演重要角色。然而，传统的NADP+检测方法无法实现NADP+的原位实时动态检测。荧光蛋白探针的出现，为体内代谢物可视化分析带来了革命性进展，但针对NADP+的检测工具仍然匮乏。本项目旨在基于理性设计与合成生物学技术，发展高性能NADP+荧光蛋白探针。基于此探针，可在活细胞、亚细胞水平建立高时空分辨的NADP+代谢荧光成像技术，并构建转基因鼠和糖尿病鼠模型，从而分析不同生理和病理条件下NADP+的实时动态水平。本项目为氧化还原代谢疾病诊疗和药物开发提供了创新性工具，有重要的科学意义。

Oxidized nicotinamide adenine dinucleotide phosphate, NADP+, is a key coenzyme, which widely exists among all living organisms. It is not only in the center position of redox homeostasis maintenance, but also involved in multiple metabolic processes, such as the pentose phosphate pathway, fatty acid synthesis, detoxification reactions, etc. On the other hand, NADP+ also plays an important role in cancer, diabetes, neurological diseases and other pathological processes. However, it is impossible to realize real-time monitoring of NADP+ in situ by traditional analytical methods. The emergence of fluorescent protein sensors has brought revolutionary advances to the visual analysis of metabolites in vivo. Nevertheless, there is a lack of effective tools in NADP+ detection. This project aims at developing high-performance genetically encoded fluorescent NADP+ indicator based on rational design and synthetic biology technology, and establishing methods of high time and spatial resolution for imaging and detecting NADP+ at cellular and subcellular levels. Moreover, we will build transgenic mice and diabetic mice models, analyze the real-time dynamic level of NADP+ under different physiological and pathological conditions. This project provides innovative tools for the diagnosis and treatment of redox metabolic diseases and drug development, which will be valuable to scientific research.