NMR and Metabolomics Core

项目总结(见说明)： 核磁共振核心的主要目的是为目标大分子的结构分析、它们的相互作用以及与从电子搜索中获得的候选药物分子以及癌细胞和组织的优化和代谢组学提供基础设施和支持。这包括稳定的同位素标记战略，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，通过稳定同位素分辨代谢组学(SIRM)提供关于特定代谢途径的更详细信息。这包括对大分子及其与小分子的相互作用的核磁共振结构和生物物理分析，以及作为药物发现/开发过程的一部分广泛使用核心的代谢组学能力。使用该设施的研究项目中，有很大一部分是翻译的，使用的是纯化的成分，以及动物模型和人类受试者。基于核磁共振的研究与其他核心的激活同步进行，特别是建模核心，并在未来与转基因小鼠核心一起进行。核磁共振是为数不多的在活体内提供局部成像和高分辨率、高信息含量光谱的技术之一。这将是核心的一个主要新方向。 核心的总体目标将通过以下具体目标实现： 1.为表征大分子及其相互作用提供核磁共振仪器和专业知识；2.为代谢组学研究提供仪器和专业知识；3.为药物发现和药物开发提供基于结构的药物设计；4.在小动物身上开发和实施新的实验和能力，包括体内稳定同位素分解的代谢组学；5.教育成员 为他们的研究项目提供核磁共振的具体能力；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。 就癌症中心和大学的总体研究任务而言，这些目标是对其他核心的目标的补充。

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.