Instrumentation Upgrade: acquisition of an intermediate voltage TEM

描述(申请人提供)：项目摘要在这里，我们寻求资金购买一个现代的，中压(300千伏)传输电子显微镜(F30 Polara)。该显微镜将取代桑福德-伯纳姆医学研究所(SBMRI)现有的FEI Tecnai F20。F30将被整合到一个现有的单元中，该单元由低温TEMS和辅助设备组成。它将通过样品处理的半自动化和更强大的筛选能力、更好和更强大的电子光学、更稳定的液氮稳定阶段和更高的倾斜系列完成率，提供在液氮温度下获取更强大、高质量/高通量的低温层析成像数据的手段。总而言之，这一升级将使我们能够优化来自我们科学团队的广泛生物样本的数据质量和分辨率，使我们能够关联分子机制和功能输出，提供规模集成的疾病模型，并为新疗法的开发提供新的视角。拟议的仪器升级将支持来自SBMRI的科学家团队以及来自TSRI、UCSD、加州大学洛杉矶分校、耶鲁大学、弗吉尼亚大学医学院、哈佛医学院、斯托尔斯医学研究所和新墨西哥大学健康科学中心的研究人员。所有这些研究人员都由美国国立卫生研究院的项目拨款资助，在发育生物学、炎症、先天免疫、骨矿化、转移和传染病等领域进行广泛的健康相关研究。本申请中重点介绍的所有项目都采用冷冻断层成像，范围从单大分子组装结构确定的断层扫描到原位全细胞断层扫描。这些项目只是一个潜在的更大的项目库的代表，这些项目可以从获得这一专门的、现代的冷冻断层扫描F30范围中获得极大的好处。

DESCRIPTION (provided by applicant): PROJECT SUMMARY Here, we seek funding to purchase a modern, intermediate voltage (300 kV) transmission electron microscope (F30 Polara). This microscope will replace the existing FEI Tecnai F20 at Sanford-Burnham Medical Research Institute (SBMRI). The F30 will be integrated into an existing unit that comprises of cryo-TEMs and ancillary equipment. It will provide the means for a more robust, high-quality/high-throughput cryo-tomography data acquisition at LN2 temperatures by semi-automation of sample handling and more robust screening capabilities, better and more powerful electron optics, LN2 stable stage and higher rates of tilt series completion. Together, this upgrade will allow us to optimize data quality and resolution for a broad range of biological samples from our scientific teams, enabling us to correlate molecular mechanisms and functional outputs, to provide scale-integrated models of disease, and to provide new perspectives for the development of new therapeutics. The proposed instrumentation upgrade will support teams of scientists from SBMRI and researchers from TSRI, UCSD, UCLA, Yale University, University of Virginia School of Medicine, Harvard Medical School, Stowers Institute for Medical Research, and the University of New Mexico Health Sciences Center. All these researchers are funded through project grants from the NIH to pursue a broad range of health-related studies in the areas of developmental biology, inflammation, innate immunity, bone mineralization, metastasis, and infectious diseases. All of the projects highlighted in this application employ cryo-tomography imaging, ranging from tomography of single macromolecular assembly structure determination to in-situ whole cell tomography. These projects are only representatives of a potentially much larger pool of projects that could greatly benefit from access to this dedicated, modern cryo-tomography F30 scope.