The self-conditioning gate - are all nuclear pores equal?

自调节门——所有核孔都是平等的吗？

• 批准号: 1917206
• 负责人: David Grunwald
• 金额: $ 90万
• 依托单位: University of Massachusetts Medical School
• 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: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1917206&HistoricalAwards=false
• 关键词: self; conditioning; gate; nuclear; pores

This project furthers our principle understanding of the function of a key machine in eukaryotic cells, the nuclear pore complex, in space and time. Increasing our knowledge on the heterogeneity of functions this mega-complex has in the cell is of crucial importance to understand how cells regulate their response to external stimuli like stress or immune challenges differently to steady state processes such as cell growth. Besides addressing conceptual challenges and providing technological progress to its field, the project integrates undergraduate (REU) and high school students (RAHSS) in a productive and meaningful manner in the research while fostering and supporting underserved students for careers in STEM fields. Integration of undergraduate and high school students in turn provides a unique opportunity for graduate students and post docs to become effective mentors.Using light microscopy technology that cannot be obtained from commercial sources, single mRNAs, protein factors and nuclear pore complexes will be monitored simultaneously in 3D with millisecond time resolution and nanometer registration precision in living cells using minimal light dosages. This data will contain rich information about the efficiencies of transport of proteins and mRNAs through nuclear pore complexes as well as how different biochemical transport pathways are regulated in the cell. The project sets out to prove the notion of all nuclear pore complexes being equal does not hold true on a dynamic functional basis inside the cell.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.

这个项目进一步加深了我们对真核细胞中一个关键机器--核孔复合体--在空间和时间上的功能的原理性理解。增加我们对这种巨型复合物在细胞中的功能异质性的了解对于理解细胞如何调节其对外部刺激（如压力或免疫挑战）的反应与稳态过程（如细胞生长）不同至关重要。除了解决概念上的挑战和提供技术进步，其领域，该项目将本科生（REU）和高中生（RAHSS）以富有成效和有意义的方式整合在研究中，同时培养和支持服务不足的学生在STEM领域的职业生涯。本科生和高中生的融合反过来为研究生和博士后提供了一个独特的机会，成为有效的导师。使用无法从商业来源获得的光学显微镜技术，将以毫秒级的时间分辨率和纳米级的配准精度在活细胞中使用最小的光剂量同时监测单个mRNA，蛋白质因子和核孔复合物。这些数据将包含有关蛋白质和mRNA通过核孔复合物的转运效率以及细胞中不同生化转运途径如何调节的丰富信息。该项目旨在证明所有核孔复合物都是平等的概念并不适用于细胞内的动态功能基础。该奖项反映了NSF的法定使命，并被认为值得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来支持。

项目成果

Micro-Meta App: an interactive tool for collecting microscopy metadata based on community specifications.

Micro-Meta应用程序：一种基于社区规范收集显微镜元数据的交互式工具。

• DOI: 10.1038/s41592-021-01315-z
• 发表时间: 2021-12
• 期刊: Nature methods
• 影响因子: 48
• 作者: Rigano A;Ehmsen S;Öztürk SU;Ryan J;Balashov A;Hammer M;Kirli K;Boehm U;Brown CM;Bellve K;Chambers JJ;Cosolo A;Coleman RA;Faklaris O;Fogarty KE;Guilbert T;Hamacher AB;Itano MS;Keeley DP;Kunis S;Lacoste J;Laude A;Ma WY;Marcello M;Montero-Llopis P;Nelson G;Nitschke R;Pimentel JA;Weidtkamp-Peters S;Park PJ;Alver BH;Grunwald D;Strambio-De-Castillia C
• 通讯作者: Strambio-De-Castillia C

Towards community-driven metadata standards for light microscopy: tiered specifications extending the OME model.

• DOI: 10.1038/s41592-021-01327-9
• 发表时间: 2021-12
• 期刊: NATURE METHODS
• 影响因子: 48
• 作者: Hammer, Mathias;Huisman, Maximiliaan;Rigano, Alessandro;Boehm, Ulrike;Chambers, James J.;Gaudreault, Nathalie;North, Alison J.;Pimentel, Jaime A.;Sudar, Damir;Bajcsy, Peter;Brown, Claire M.;Corbett, Alexander D.;Faklaris, Orestis;Lacoste, Judith;Laude, Alex;Nelson, Glyn;Nitschke, Roland;Farzam, Farzin;Smith, Carlas S.;Grunwald, David;Strambio-De-Castillia, Caterina
• 通讯作者: Strambio-De-Castillia, Caterina

Community-developed checklists for publishing images and image analyses

社区开发的用于发布图像和图像分析的清单

• DOI: 10.1038/s41592-023-01987-9
• 发表时间: 2023
• 期刊: Nature Methods
• 影响因子: 48
• 作者: Schmied, Christopher;Nelson, Michael S.;Avilov, Sergiy;Bakker, Gert-Jan;Bertocchi, Cristina;Bischof, Johanna;Boehm, Ulrike;Brocher, Jan;Carvalho, Mariana T.;Chiritescu, Catalin
• 通讯作者: Chiritescu, Catalin