Cryo-TEM for Biomedical Research

摘要 布朗大学请求支持冻土带冷冻透射电子显微镜(Cryo-TEM)。这 将使用显微镜通过单颗粒分析来检查蛋白质结构，以更好地了解基本情况 关于健康和疾病中的生化过程。在苔原低温透射电子显微镜上成像的玻璃化样品可以 在国家低温电子显微镜中心以高分辨率回收用于低温电子显微镜(CRYO-EM)。此外， 所要求的显微镜将被用作对小泡、细胞器和神经进行成像的标准透射电子显微镜 超薄组织切片中的连接。苔原低温瞬变电磁法将取代已有39年历史的瞬变电磁法 生物学和医学，并将成为罗德州第一台能够进行单粒子分析的低温电子显微镜 小岛。16名调查人员将立即使用低温瞬变显微镜。这16个用户组总共获得了资金 由NIH提供的31笔赠款，涵盖了从抗生素耐药性到不孕不育的生物医学研究的广泛领域 衰老和神经退行性疾病。所有主要用户都对低温EM有很大的需求。这些专业 用户要么去了州外的低温EM，要么使用了其他没有回答问题的技术， 尤其是在研究大型动态蛋白质时。次要用户计划将请求的显微镜用作 由于所需设备未安装而被搁置的标准瞬变电磁或低温电磁项目 在布朗大学提供。所有主要和次要用户都有可以立即受益的研究项目 从提议的设备中。拟议的成像系统的影响将超出以下项目 主要用户和次要用户，因为显微镜将向更广泛的科学领域提供 罗德岛的社区，那里有700多个NIH资助的正在进行的项目。显微镜将安装在 Leduc生物成像设备，它拥有维护仪器和培训用户的技术专长。 此外，生化样本的优化和评估将得到布朗大学结构性研究的支持 生物设施以及数据存储和分析将由计算和可视化中心提供支持。 乐迪克生物成像设施有一个基础广泛的咨询委员会，良好的记录保持 各种高端成像系统，以及强大的机构支持，这保证了仪器的 将在未来几年发挥其最大潜力。

Summary Brown University requests support for a Tundra Cryo-Transmission Electron Microscope (Cryo-TEM). This microscope will be used to examine protein structure by single particle analysis for a better basic understanding of biochemical processes in health and disease. Vitrified samples imaged on the Tundra Cryo-TEM can be recovered for cryo-electron microscopy (cryo-EM) at high resolution in national cryo-EM centers. In addition, the requested microscope will be used as a standard TEM for imaging small vesicles, organelles and neural connections in ultrathin tissue sections. The Tundra Cryo-TEM will replace a 39-year-old TEM in the Division of Biology and Medicine and will be the first Cryo-TEM capable of single particle analysis in the State of Rhode Island. The Cryo-TEM will be used immediately by 16 investigators. Collectively, these 16 user groups are funded by 31 NIH grants, covering a broad area in biomedical research ranging from antibiotic resistance and infertility to aging and neurodegenerative disease. All major users have a substantial need for cryo-EM. These major users either traveled out of state for cryo-EM or used other technologies that left questions unanswered, especially when studying large dynamic proteins. The minor users plan to use the requested microscope as a standard TEM or have cryo-EM projects that were put on hold since the required equipment has not been available at Brown University. All major and minor users have research projects that would immediately benefit from the proposed equipment. The impact of the proposed imaging system will extend beyond the projects of the major and minor users, since the microscope will be made be made available to the broader scientific community in Rhode Island, which has over 700 active NIH-funded projects. The microscope will be set up in the Leduc Bioimaging Facility, which has the technical expertise to maintain the instrument and train its users. In addition, biochemical sample optimization and evaluation will be supported by Brown University’s Structural Biology Facility and data storage and analysis will be supported by the Center for Computation and Visualization. The Leduc Bioimaging Facility has a broadly-based Advisory Committee, an excellent track record maintaining various high-end imaging systems, and strong institutional support, which guarantees that the instrumentation will be used to its maximum potential for years to come.