Purchase of a 600 MHz NMR Console and Probes

描述(由申请人提供)：一个由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核磁共振主要用户组正在申请资金，用于购买配备三重共振低温探头的布鲁克或瓦里安600 MHz核磁共振光谱仪控制台。所要求的控制台将取代约翰霍普金斯医学院(SOM)核磁共振设施中一个已有18年历史的控制台，该控制台最近发生了灾难性故障，已退役。目前，SOM没有可运行的高场光谱仪，用户基础的研究计划已受到严重损害。虽然用户可以使用位于艺术和科学园区的其他光谱仪，但这些机器现在经常被使用，数据获取的等待时间很长，这现在减缓了研究调查。用户分布在约翰·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对生物大分子的结构、机理和动力学的基础研究。这一仪器将在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影响广泛的与健康相关的基础研究项目。此次收购将使霍普金斯医学院的核磁共振设施恢复到最先进的水平，并将使这些研究项目能够利用磁铁和探头技术，这些技术对于在稀薄条件下研究大生物分子至关重要。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复合体的光谱分辨率至关重要。此外，获取核磁共振数据的灵敏度将至少是目前600 MHz仪器的1.7倍，这将加强对生物分子的研究，这些生物分子由于核磁共振信号固有的弱、低溶解度、低样品可用性或短期稳定性而具有挑战性。此次收购将挽救霍普金斯大学两个校区核磁共振设施的超额认购，这些超额认购源于最近两个核磁共振教员招聘以及几个广泛使用该设施仪器的新研究项目。 与公共卫生有关：需要资金以获得替换的600兆赫核磁共振光谱仪控制台和冷冻探头系统，用于在酶DNA修复、蛋白质-核酸相互作用、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进行与健康有关的结构和机制研究。

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.