NMR and Metabolomics Core

项目总结（见说明）： NMR核心的主要目的是为靶大分子的结构分析、它们的相互作用以及与从计算机搜索和优化以及癌细胞和组织的代谢组学中获得的候选药物分子的相互作用提供基础设施和支持。这包括稳定同位素标记策略，包括N-15和C-13前体。我们的目标仍然是简化数据收集和分析，并引入新的标记策略，通过稳定同位素解析代谢组学（SIRM）提供有关特定代谢途径的更详细信息。这包括大分子及其与小分子相互作用的NMR结构和生物物理分析，以及作为药物发现/开发过程一部分的Core代谢组学功能的广泛使用。使用该设施的很大一部分研究项目是转化的，使用纯化的成分，以及动物模型和人类受试者。基于NMR的研究与其他核心的激活协同进行，特别是建模核心，并且在未来与转基因小鼠核心一起进行。NMR是少数几种在体内提供局部成像和高分辨率、高信息含量光谱学的技术之一。这将是核心的一个主要新方向。 核心方案的总体目标将通过以下具体目标实现： 1.提供核磁共振仪器和专业知识来表征大分子及其相互作用; 2.为代谢组学研究提供仪器和专业知识; 3.促进基于结构的药物设计用于药物发现和药物开发; 4.开发和实施新的实验和能力，包括在小动物体内的稳定同位素解析代谢组学; 5.教育会员 社区对核磁共振的具体能力，为他们的研究项目; 6.为学生和研究员提供癌症生物化学和药物开发方面的培训。 这些目标补充了癌症中心和大学的整体研究使命方面的其他核心。

PROJECT SUMMARY (See instructions): The primary aims of the NMR core are to provide infrastructure and support for structural analysis of target macromolecules, their mutual interactions and with candidate drug molecules obtained from in silico searches and optimization and metabolomics of cancer cells and tissue. This includes stable isotope labeling strategies including N-15 and C-13 precursors. Our goals continue to be to streamline both data collection and analysis as well as introduce new labeling strategies to provide more detailed information about specific metabolic pathways, via Stable Isotope Resolved Metabolomics (SIRM). This includes NMR structural and biophysical analysis of macromolecules and their interactions with small molecules, as well as extensive use of the metabolomics capabilities of the Core as a part of the drug discovery/development process. A large fraction of research projects that use the facility are translational, using purified components, as well as animal models and human subjects. The NMR-based studies operate in tandem with activates of other Cores, especially the Modeling Core and, in the future, with the Transgenic Mouse Core. NMR is one of the few techniques that provides localized imaging and high resolution, high information content spectroscopy in vivo. This will be a major new direction of the Core. The overall goals of the Core will be achieved via the following Specific Aims: 1. Provide NMR instrumentation and expertise for characterizing macromolecules and their interactions; 2. Provide the instrumentation and expertise for metabolomics studies; 3. Facilitate structure-based drug design for drug discovery and drug development; 4. Develop and implement new experiments and capabilities including stable isotope resolved metabolomics on small animals, in vivo; 5. Educate members of the community on the specific capabilities of NMR for their research projects; 6. Provide training of students and fellows in cancer biochemistry and drug development. These Aims complement those of the other Cores in terms of the overall research mission of the Cancer Center and the University.