A Console Upgrade and Cryogenic Probe for a 500 MHz NMR System for Biomedical Res

描述（由申请人提供）：本申请要求为波士顿大学医学院用于溶液状态NMR光谱的18年前500 MHz仪器的最先进控制台升级和低温探头提供资金，该仪器不再由其制造商提供支持。这次升级将使核磁共振光谱仪的灵敏度提高一个数量级以上。所要求的控制台配备了四个通道，允许运行任何当前可用的溶液NMR实验，其中一些实验无法在波士顿大学现有的任何光谱仪上运行。在全国范围内，特别是在波士顿地区，获得高场NMR光谱仪一直受到限制，这限制了科学家解决生物医学研究中一些具有挑战性的领域的能力。升级后的500 MHz光谱仪将允许更快的数据收集，质量更高，特别是对于较大的蛋白质。这将大大提高核磁共振设施的能力。它还将使用户能够研究具有高分子量和/或有限溶解度的蛋白质和复合物的结构和动力学，这在目前的仪器上是不可能的，因为它缺乏灵敏度。九个主要用户的研究包括以下NIH资助的项目，这些项目将直接受益于最先进的500 MHz NMR光谱仪：1）心血管系统蛋白质的结构和动力学以及折叠。2)脂肪酸转运蛋白的结构生物学与动力学。3)正常和致病性Notch信号传导的机制研究。4)翻译起始的分子机制。5)核仁靶向和IVb型蛋白分泌系统。6)血浆脂蛋白和载脂蛋白：结构和生物学。7)转录因子的结构和功能。8)神经毒性朊蛋白的结构研究。9)牙周病的代谢组学。将鼓励其他研究人员使用升级后的500兆赫核磁共振波谱仪，并为他们提供仪器时间。总之，所要求的500 MHz NMR光谱仪的升级和低温探头将是波士顿大学和波士顿地区生物医学研究界的宝贵资产。它将立即影响NIH资助的多个领域的研究，特别是心血管疾病，脂肪酸转运，基因表达，蛋白质生物合成，传染病和信号转导。

DESCRIPTION (provided by applicant): This application requests funding for a state-of-the-art console upgrade and cryogenic probe for an 18 year-old 500 MHz instrument for solution state NMR spectroscopy at the Boston University School of Medicine which is no longer supported by its manufacturer. The upgrade will increase the sensitivity of the NMR spectrometer by over an order of magnitude. The requested console is equipped with four channels, which allows running any currently available solution NMR experiments, a number of which cannot be run on any of the existing spectrometers at Boston University. Access to high-field NMR spectrometers has always been limited both nationwide and specifically in the Boston area, which restricts the ability of scientists to tackle a number of challenging areas of biomedical research. The upgraded 500 MHz spectrometer will allow faster data collection, with higher quality, particularly for larger proteins. This will drastically increase the capacity of the NMR facility. It will also enable users to study the structure and dynamics of proteins and complexes with high molecular weights and/or limited solubility, which are not possible on the current instrument due to its lack of sensitivity. The research of the nine major users includes the following NIH-funded projects that will directly benefit from a state-of-the-art 500 MHz NMR spectrometer: 1) Structure and dynamics and folding of proteins of the cardiovascular system. 2) Structural biology and dynamics of fatty acid transport proteins. 3) Mechanistic studies of normal and pathogenic Notch signaling. 4) Molecular mechanisms of translation initiation. 5) Nucleolar targeting and a type IVb protein secretion system. 6) Plasma lipoproteins and apolipoproteins: Structure and Biology. 7) Structure and function of transcription factors. 8) Structural studies of neurotoxic prion proteins. 9) Metabolomics of periodontal disease. Use of the upgraded 500 MHz NMR spectrometer by other researchers will be encouraged and instrument time will be made available for them. In summary, the requested upgrade and cryogenic probe for a 500 MHz NMR spectrometer will be a valuable asset for the biomedical research community at Boston University and the Boston area. It will immediately impact active NIH-funded research in multiple areas, in particular cardiovascular disease, fatty acid transport, gene expression, protein biogenesis, infectious disease and signal transduction.