Purchase of a 600 MHz NMR Console and Probes

购买 600 MHz NMR 控制台和探头

• 批准号: 8051342
• 负责人: JAMES T. STIVERS
• 金额: $ 55万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8051342
• 关键词: 18 year old; Area; Arts; Basic Science; Biological; Carcinogenesis Mechanism; Chemicals; Complex; DNA; DNA repair protein; DNA-Protein Interaction; Data; Degradation Pathway; Faculty; Failure; Funding; Health; Heteronuclear NMR; Investigation; Life; Methods; Minor; Molecular; Nucleic Acids; Protein-Folding Disease; Proteins; Protons; Research; Research Personnel; Research Project Grants; Resolution; Sampling; Schools; Science; Signal Transduction; Solubility; Structure; System; Technology; Time; United States National Institutes of Health; Universities; base; cryogenics; data acquisition; fundamental research; instrument; instrumentation; macromolecule; medical schools; programs; protein degradation

DESCRIPTION (provided by applicant): An NMR major users group consisting of 5 NIH-funded investigators and 9 minor users with NIH or NSF funding is applying for funds for the purchase of a Bruker or Varian 600 MHz NMR spectrometer console equipped with a triple resonance cryogenic probe. The requested console will replace, at Johns Hopkins School of Medicine (SOM) NMR facility, an 18 year old console which recently suffered a catastrophic failure and has been decommissioned. There is currently no operational high-field spectrometer at the SOM, and the research programs of the user base have been significantly impaired. Although the users have access to other spectrometers located at the Arts and Science campus, these machines are now constantly utilized with significant waiting times for data acquisition that are now slowing down research investigations. The users are located across six Departments and three Schools of the Johns Hopkins University (JHU) and the requested instrument will be used to advance fundamental research into the structure, mechanism and dynamics of biological macromolecules using multi-dimensional heteronuclear NMR methods. This instrumentation will impact a wide range of health related basic research projects in the areas of DNA repair, protein-DNA interactions, protein stability, molecular mechanisms of carcinogenesis, protein folding diseases, protein degradation pathways and signal transduction mechanisms. This acquisition will restore the NMR facility at Hopkins School of Medicine to a state-of-the-art level, and will allow these research programs to take advantage of magnet and probe technologies that are essential for studying large biological molecules under dilute conditions. The new system will provide the chemical shift dispersion and sensitivity that is essential for studying denatured states of proteins, aliphatic proton regions of nucleic acids, and obtaining spectral resolution of native 20-40 kDa proteins and large protein-DNA complexes that are now under study. In addition, NMR data will be acquired with sensitivity that will be at least 1.7-fold greater than the current 600 MHz instrument, enhancing the study of biological molecules that are challenging due to inherent weakness of the NMR signals, low solubility, low sample availability, or short-lived stability. This acquisition will rescue oversubscription of the Hopkins NMR facilities on both campuses arising from two recent NMR faculty recruitments and also several new research projects that extensively utilize the instruments at the facility. PUBLIC HEALTH RELEVANCE: Funds are requested to obtain a replacement 600 MHz NMR spectrometer console and cryoprobe system that will be used for health related structural and mechanistic research in the areas of enzymatic DNA repair, protein-nucleic acid interactions, molecular mechanisms of carcinogenesis, protein folding diseases, protein degradation pathways and signal transduction mechanisms.

描述（由申请人提供）：由 5 名 NIH 资助的研究人员和 9 名 NIH 或 NSF 资助的次要用户组成的 NMR 主要用户组正在申请资金购买配备三重共振的 Bruker 或 Varian 600 MHz NMR 波谱仪控制台低温探针。所请求的控制台将取代约翰霍普金斯大学医学院 (SOM) NMR 设施中一台已有 18 年历史的控制台，该控制台最近遭遇了灾难性故障，现已退役。目前，SOM 没有可运行的高场光谱仪，用户群的研究计划已受到严重损害。尽管用户可以使用位于艺术和科学校区的其他光谱仪，但这些机器现在经常被使用，数据采集的等待时间很长，这正在减慢研究调查的速度。用户遍布约翰·霍普金斯大学 (JHU) 的六个系和三个学院，所需的仪器将用于利用多维异核核磁共振方法推进生物大分子结构、机制和动力学的基础研究。该仪器将影响 DNA 修复、蛋白质-DNA 相互作用、蛋白质稳定性、致癌分子机制、蛋白质折叠疾病、蛋白质降解途径和信号转导机制等领域的广泛健康相关基础研究项目。此次收购将使霍普金斯大学医学院的核磁共振设施恢复到最先进的水平，并使这些研究项目能够利用磁铁和探针技术，这些技术对于在稀释条件下研究大型生物分子至关重要。新系统将提供化学位移色散和灵敏度，这对于研究蛋白质的变性状态、核酸的脂肪族质子区域以及获得目前正在研究的天然 20-40 kDa 蛋白质和大型蛋白质-DNA 复合物的光谱分辨率至关重要。此外，NMR 数据的采集灵敏度将比当前 600 MHz 仪器至少高 1.7 倍，从而增强对由于 NMR 信号固有弱点、溶解度低、样品可用性低而具有挑战性的生物分子的研究，或短暂的稳定。此次收购将挽救霍普金斯大学两个校区 NMR 设施的超额认购，这些设施是由于最近两次 NMR 教员招聘以及广泛使用该设施仪器的几个新研究项目而引起的。 公共健康相关性：需要资金来获得替换的 600 MHz NMR 波谱仪控制台和冷冻探针系统，该系统将用于酶促 DNA 修复、蛋白质-核酸相互作用、致癌分子机制、蛋白质等领域的健康相关结构和机制研究折叠疾病、蛋白质降解途径和信号转导机制。