Biological Soft X-ray Tomography at the Advanced Light Source

先进光源下的生物软 X 射线断层扫描

• 批准号: 10710224
• 负责人: Carolyn A Larabell
• 金额: $ 88.82万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10710224
• 关键词: 3-Dimensional; Acceleration; Adherence; Advisory Committees; Algorithms; Area; Beer; Biochemical; Biological; Biomedical Research; Biophysics; Calibration; Cell Size; Cells; Cellular biology; Chemicals; Communication; Communities; Computer software; Contrast Media; Cryopreservation; Data; Data Analyses; Data Collection; Development; Diabetes Mellitus; Disease; Disseminated Malignant Neoplasm; Education and Outreach; Electron Microscopy; Ensure; Eukaryotic Cell; Feedback; Fluorescence; Fluorescence Microscopy; Funding; Future; Home; Hour; Human; Image; Imaging Techniques; Imaging technology; Individual; Infrastructure; Institution; Laboratories; Laws; Length; Light; Maintenance; Microscope; Modeling; Molecular Machines; Monitor; Neurodegenerative Disorders; Online Systems; Organism; Parasites; Peer Review; Persons; Preparation; Process; Productivity; Qualifying; Questionnaires; Reporting; Research; Research Personnel; Resolution; Resources; Roentgen Rays; Running; Safety; Schedule; Services; Shapes; Site; Source; Specimen; Stains; Synchrotrons; System; Technology; Thick; Time; Training; Training Programs; Visit; Visualization; Work; X-Ray Tomography; absorption; aged; attenuation; base; beamline; biomedical facility; biomedical imaging; cell type; cellular imaging; computerized data processing; computing resources; contrast imaging; cryogenics; end of life; experience; human disease; human imaging; imaging modality; improved; insight; instrument; instrumentation; novel therapeutics; operation; outreach; programs; reconstruction; repaired; tomography; transmission process; ultra high resolution; user-friendly

Project Summary/Abstract The National Center for X-ray Tomography (NCXT) is a full-service, user facility for biomedical imaging and research. NCXT Users, whether working on site or remotely, have access to specialized microscopes and imaging techniques, in particular soft x-ray tomography (SXT) and super-resolution cryogenic fluorescence tomography (SR-CFT). In the US, these imaging modalities are only available at the NCXT. SXT microscopes visualize and quantify the mesoscale organization of biological cells, including large eukaryotic cells. No stains or contrast agents are required for SXT imaging. Before being imaged by the NCXT's transmission soft x-ray microscope at the Advanced Light Source, cells are rapidly cryo-preserved; the only pre-imaging step required. SXT is highly complementary to other imaging modalities, particularly fluorescence and electron microscopies. Mesoscale, 3D SXT reconstructions of an entire cell act as a framework for the interpretation of other types of imaging and biophysical data, allowing them to be viewed in the context of the whole cell. XM2 is currently the only microscope of its kind in the Nation. The requested P30 funding will support the day-to-day operation of XM-2, together with the associated user program and specimen preparation laboratories, and a program of upgrades to our software/computing resources. During the funding cycle, we will achieve the following specific aims: Aim 1: Give the biomedical research community access to soft x-ray tomography (SXT). The work of this aim ensures imaging cells by SXT remains an option open to US researchers. Significant consideration will be given to making the Resource as user-friendly as possible, particular towards the community of researchers that work remotely. Aim 2: Maintain and calibrate XM-2, the NCXT operated soft x-ray microscope at the ALS. As with all synchrotron beamlines, XM-2 is a sophisticated instrument that requires regular maintenance and calibration. We will take a programmatic approach to ensure XM-2 is robust, reliable, and operates with minimum unscheduled downtime. Aim 3: Implement upgrades and enhancements to ensure the NCXT remains `state-of-the-art.' Over the timescale of the funding cycle, new hardware, software, and algorithms will become available, and some existing components will reach their end-of-life. We will, therefore, carry out upgrades and enhancements to maintain the NCXT at the `state-of-the-art.'

项目概要/摘要 国家 X 射线断层扫描中心 (NCXT) 是一个提供全方位服务的用户设施 生物医学成像和研究。 NCXT 用户，无论是现场工作还是远程工作， 能够使用专门的显微镜和成像技术，特别是软 X 射线 断层扫描 (SXT) 和超分辨率低温荧光 断层扫描（SR-CFT）。在美国，这些成像方式仅在 NCXT。 SXT 显微镜可视化并量化生物细胞的介观组织， 包括大型真核细胞。 SXT 不需要染色剂或造影剂 成像。在由 NCXT 的透射软 X 射线显微镜成像之前 先进光源，细胞快速冷冻保存；唯一的预成像步骤 必需的。 SXT 与其他成像方式高度互补，特别是荧光和 电子显微镜。整个细胞的中尺度 3D SXT 重建充当 解释其他类型的成像和生物物理数据的框架， 允许在整个细胞的背景下查看它们。 XM2 是目前国内唯一的同类显微镜。要求的P30 资金将支持 XM-2 以及相关的日常运营 用户计划和样本制备实验室，以及我们的升级计划 软件/计算资源。在融资周期内，我们将实现以下目标 具体目标： 目标 1：为生物医学研究界提供软 X 射线 断层扫描（SXT）。这一目标的工作确保 SXT 成像细胞仍然是 选项向美国研究人员开放。将认真考虑使 资源尽可能方便用户，特别是对研究人员社区 远程工作。 目标 2：维护和校准 XM-2，NCXT 操作的软 X 射线 ALS 的显微镜。与所有同步加速器光束线一样，XM-2 是一种先进的 需要定期维护和校准的仪器。我们将采取一个 编程方法确保 XM-2 稳健、可靠，并以最少的成本运行 计划外停机。 目标 3：实施升级和增强以确保 NCXT 仍然是“最先进的”。在融资周期的时间范围内，新硬件、 软件和算法将变得可用，并且一些现有组件将变得可用 到达生命的终点。因此，我们将进行升级和增强 使 NCXT 保持“最先进”。

项目成果

Heterochromatin-mediated gene silencing facilitates the diversification of olfactory neurons.

• DOI: 10.1016/j.celrep.2014.10.001
• 发表时间: 2014-11-06
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Lyons DB;Magklara A;Goh T;Sampath SC;Schaefer A;Schotta G;Lomvardas S
• 通讯作者: Lomvardas S

Nuclear architecture as an epigenetic regulator of neural development and function.

• DOI: 10.1016/j.neuroscience.2014.01.044
• 发表时间: 2014-04-04
• 期刊: NEUROSCIENCE
• 影响因子: 3.3
• 作者: Alexander, J. M.;Lomvardas, S.
• 通讯作者: Lomvardas, S.

Using soft X-ray tomography for rapid whole-cell quantitative imaging of SARS-CoV-2-infected cells.

• DOI: 10.1016/j.crmeth.2021.100117
• 发表时间: 2021-11-22
• 期刊: Cell reports methods
• 作者: Loconte V;Chen JH;Cortese M;Ekman A;Le Gros MA;Larabell C;Bartenschlager R;Weinhardt V
• 通讯作者: Weinhardt V

Enhancer interaction networks as a means for singular olfactory receptor expression.

• DOI: 10.1016/j.cell.2014.09.033
• 发表时间: 2014-10-23
• 期刊: Cell
• 影响因子: 64.5
• 作者: Markenscoff-Papadimitriou E;Allen WE;Colquitt BM;Goh T;Murphy KK;Monahan K;Mosley CP;Ahituv N;Lomvardas S
• 通讯作者: Lomvardas S

Stochastic gene expression in mammals: lessons from olfaction.

• DOI: 10.1016/j.tcb.2013.04.005
• 发表时间: 2013-09
• 期刊: TRENDS IN CELL BIOLOGY
• 影响因子: 19
• 作者: Magklara, Angeliki;Lomvardas, Stavros
• 通讯作者: Lomvardas, Stavros