MRI: Acquisition of Aquilos Dual-Beam Microscope

MRI：购买 Aquilos 双光束显微镜

• 批准号: 1920374
• 负责人: Elizabeth Villa
• 金额: $ 89.86万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2022-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1920374&HistoricalAwards=false
• 关键词: MRI; Acquisition; Aquilos; Dual; Beam

An award is made to the University of California San Diego to support the acquisition of a cryo-dual beam microscope to enable the three dimensional visualization of cells at the level of the structure of individual biomolecules. This technology will enable the development of completely novel hypothesis on how molecules perform their function within the molecular landscapes that they operate in. This project will realize this potential for laboratories at UC San Diego, and will extend the training opportunities from technically trained scientists to non-expert users, effectively democratizing this technology and training the next generation of instrumentalists from diverse backgrounds. Furthermore, the molecular landscapes that this project will reveal are great teaching and dissemination tools for general audiences, including the creation and circulation of virtual reality and videos that allow users to navigate and explore cellular territories from within. The acquisition of this instrument will support research projects that aim to observe intricate molecular networks in their natural environment. The scientific projects it will support span from technical projects that aim to develop new methodologies that will leverage the use of cryo-FIB milling for structural cell biology, to biologically driven projects with goals of unveiling the molecular mechanisms that result from specialized molecular networks in various model systems in cell biology. Method-related projects include development of novel computational algorithms to identify proteins within the molecular panoramas and enabling simulations of entire cells to predict cellular behavior under a variety of perturbations. Biologically driven projects include: unveiling unexplored mechanisms in bacterial cell biology, such as how bacterial cells divide and differentiate, how they respond to viral infection or keep track of time; the study of fundamental processes in the nucleus of eukaryotic cells such as how the genome organizes in 3-D and how this architecture determines the state of the cell. Together with future projects that will be enabled by this technology, the awarded project has the potential to make transformative discoveries that will unleash yet-unimagined hypothesis of cellular mechanisms in a wide range of biological scenarios.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

向加州圣地亚哥大学颁发了一个奖项，以支持获得一台低温双光束显微镜，从而能够在单个生物分子的结构水平上实现细胞的三维可视化。这项技术将使开发一个全新的假设成为可能，即分子如何在其运作的分子景观中发挥其功能。该项目将实现加州大学圣地亚哥分校实验室的这一潜力，并将培训机会从受过技术培训的科学家扩展到非专家用户，有效地使这项技术民主化，并培训来自不同背景的下一代乐器演奏家。 此外，该项目将揭示的分子景观是面向普通观众的伟大教学和传播工具，包括虚拟现实和视频的创建和传播，允许用户从内部导航和探索细胞领域。 该仪器的获得将支持旨在观察自然环境中复杂分子网络的研究项目。它将支持的科学项目包括旨在开发新方法的技术项目，这些方法将利用cryo-FIB研磨用于结构细胞生物学，以及生物驱动的项目，其目标是揭示细胞生物学中各种模型系统中的专门分子网络产生的分子机制。与方法相关的项目包括开发新的计算算法来识别分子内的蛋白质，并模拟整个细胞来预测各种扰动下的细胞行为。 生物学驱动的项目包括：揭示细菌细胞生物学中未探索的机制，例如细菌细胞如何分裂和分化，它们如何对病毒感染作出反应或跟踪时间;研究真核细胞核中的基本过程，例如基因组如何在3D中组织以及这种结构如何决定细胞的状态。该奖项与未来将由该技术支持的项目一起，有可能做出变革性的发现，将在广泛的生物场景中揭示尚未想象到的细胞机制假设。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

HSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells.

• DOI: 10.1126/science.abb4309
• 发表时间: 2021-02-05
• 期刊: Science (New York, N.Y.)
• 作者: Yu H;Lu S;Gasior K;Singh D;Vazquez-Sanchez S;Tapia O;Toprani D;Beccari MS;Yates JR 3rd;Da Cruz S;Newby JM;Lafarga M;Gladfelter AS;Villa E;Cleveland DW
• 通讯作者: Cleveland DW

The material properties of a bacterial-derived biomolecular condensate tune biological function in natural and synthetic systems.

天然和合成系统中细菌衍生的生物分子冷凝物调谐生物学功能的材料特性。

• DOI: 10.1038/s41467-022-33221-z
• 发表时间: 2022-09-26
• 期刊: Nature communications
• 影响因子: 16.6

Entropy-regularized deconvolution of cellular cryotransmission electron tomograms.

• DOI: 10.1073/pnas.2108738118
• 发表时间: 2021-12-14
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Croxford M;Elbaum M;Arigovindan M;Kam Z;Agard D;Villa E;Sedat J
• 通讯作者: Sedat J

A cytoskeletal vortex drives phage nucleus rotation during jumbo phage replication in E. coli.

• DOI: 10.1016/j.celrep.2022.111179
• 发表时间: 2022-08-16
• 期刊: CELL REPORTS
• 影响因子: 8.8
• 作者: Birkholz, Erica A.;Laughlin, Thomas G.;Armbruster, Emily;Suslov, Sergey;Lee, Jina;Wittmann, Johannes;Corbett, Kevin D.;Villa, Elizabeth;Pogliano, Joe
• 通讯作者: Pogliano, Joe