CAREER: Cryo-electron tomography derived multiscale integrative modeling of subcellular organization

职业：冷冻电子断层扫描衍生的亚细胞组织多尺度综合模型

• 批准号: 2238093
• 负责人: Min Xu
• 金额: $ 53.98万
• 依托单位: Carnegie-Mellon University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2238093&HistoricalAwards=false
• 关键词: CAREER; Cryo; electron; tomography; derived

Cryo-Electron Tomography (Cryo-ET) enables the 3D visualization of subcellular structures and their spatial arrangement inside single cells in close-to-native state at submolecular resolution. This Faculty Early Career Development Program (CAREER) project aims to develop computational methods to integrate cryo-ET and fluorescence microscopy in order to learn which proteins are present in different cell structures and how these structures are arranged relative to each other. The research component of this proposal will contribute novel computational methods and open-source software that are applicable to understanding complex cellular processes in a broad range of biological studies. The educational objective of this proposal is to advance and promote the teaching and training of computational analysis and understanding of biological Images (also referred to as bioimage informatics). The research activities and outcomes will be integrated into classroom teaching, public online education, and outreach programs for various students, including underrepresented students. The broadening participation efforts will provide important training in bioimage informatics for a diverse population to meet the fast-increasing demand in this important area.The investigator’s long-term research goal is to develop computational methods for cryo-ET derived multiscale integrative modeling. This CAREER project will develop computational methods for constructing multiscale subcellular organization models of cell populations by integrating information from cryo-ET and fluorescence microscopy. The Research Plan includes three objectives: 1) constructing generative models of subcellular organization from cryo-ET images of cell populations; 2) multiscale modeling by spatial pattern matching between cryo-ET and fluorescence data; 3) inferring protein composition of macromolecular structures identified in cryo-ET. It will bring unprecedented opportunities for using Cryo-ET as a faithful and spatially precise data source for modeling subcellular organization from the submolecular scale to the cellular scale. Such modeling is essential for connecting morphology to the mechanisms that produce it. The project outputs will be available at “https://github.com/xulabs/modeling”.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.

冷冻电子断层扫描（Cryo-ET）使细胞结构的3D可视化及其在分子分辨率下接近本地状态的单细胞内的空间排列。这个教师早期职业发展计划（职业）项目旨在开发计算方法来整合冷冻-ET和荧光显微镜，以了解哪些蛋白质在不同的细胞结构中呈现，以及这些结构如何相对于彼此的布置。该提案的研究组成部分将贡献新颖的计算方法和开源软件，这些软件适用于在广泛的生物学研究中理解复杂的细胞过程。该提案的教育目标是促进和促进对生物图像的计算分析的教学和培训（也称为生物形象信息）。研究活动和成果将纳入课堂教学，公共在线教育和针对包括代表性不足的学生在内的各种学生的外展计划。扩大的参与工作将为多样性人群提供重要培训，以满足这一重要领域的快速需求。该职业项目将开发用于通过整合Cryo-ET和荧光显微镜的信息来构建细胞种群的多尺寸亚细胞组织模型的计算方法。研究计划包括三个目标：1）从细胞群体的冷冻图像中构建亚细胞组织的通用模型； 2）通过空间图案匹配冷冻-ET和荧光数据之间的多尺度建模； 3）推断在冷冻-ET中鉴定的大分子结构的蛋白质组成。它将带来前所未有的机会，将Cryo-ET用作忠实且在空间上精确的数据源，用于将亚细胞组织从分子量表建模到细胞量表。这种建模对于将形态与产生它的机制联系起来至关重要。该项目输出将在“ https://github.com/xulabs/modeling”。这项奖项中提供反映NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响审查标准，被认为是珍贵的支持。