CAREER: Development of Integrated MS Strategies for Probing Peptidergic Signaling

威斯康星大学麦迪逊分校的李凌军教授在化学学部的分析和表面化学职业项目的支持下，开发了一系列基于质谱的新策略，特别是直接从甲壳类动物（如螃蟹和龙虾）的口胃神经系统和神经血管器官中进行原位肽分析。采用超高分辨率矩阵辅助激光解吸/电离（MALDI）傅立叶变换质谱（FTMS）。此外，李教授将采用多维分离方案，结合MALDI-FTMS和电喷雾电离(ESI)-串联质谱法进行新肽测序，并使用数据库同源性搜索来发现大量新的神经肽。目的是增加对神经肽能信号的理解。李教授还计划在不同生理条件下进行肽差异显示的体内监测。总的来说，通过这项研究开发的分析工具和大量新神经肽的发现应该在分析化学和神经科学研究界产生巨大的影响。PI招募初级大学生，并让地区高中教师参与研究，以便将前沿研究更好地传播给更大的公共社区。大量的多肽负责大脑和神经系统的信号传递。了解细胞和网络水平的神经肽谱对于更好地理解神经元回路中的肽能信号传导至关重要。这项研究对脑科学有很大的潜在影响。

Professor Lingjun Li of the University of Wisconsin at Madison is supported by the Analytical and Surface Chemistry CAREER Program in the Chemistry Division to develop an array of novel mass spectrometry-based strategies, specifically, in situ peptide analysis directly from the stomatogastric nervous system and neurhemal organs of crustaceans, like the crab and the lobster, using ultra-high resolution matrix assisted laser desorption/ionization (MALDI) Fourier transform mass spectrometry (FTMS). In addition, Professor Li will employ multidimensional separation schemes coupled to both MALDI-FTMS and electrospray ionization (ESI)- tandem mass spectrometry for de novo peptide sequencing, and use database homology searching to allow the discovery of a large number of novel neuropeptides. The goal is to increase understanding of neuropeptidergic signaling. Professor Li also plans to persue the development of in vivo monitoring of peptide differential display in response to varied physiological conditions. Collectively, the analytical tools developed through this research and the discovery of a large number of novel neuropeptides should have tremendous impact in both the analytical chemistry and the neuroscience research communities. The PI recruits entry-level college students, and involves regional high school teachers in research to allow for better communication of the cutting-edge research to the greater public community. A large number of peptides are responsible for signaling in the brain and the nervous system. Knowledge of the neuropeptide profile at the cellular and network level is critical for a better understanding of peptidergic signaling in neuronal circuitry. This research has a high potential impact on brain science.