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Molecular Paleontology to Uncover the Origin and Evolution of the Nuclear Pore Complex

分子古生物学揭示核孔复合体的起源和演化

基本信息

批准号：
1818129
负责人：
Samson Obado
金额：
$ 103.4万
依托单位：
Rockefeller University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1818129&HistoricalAwards=false
关键词：
Molecular Paleontology Uncover Origin Evolution

项目摘要

Unicellular organisms that lack internal structures such as a nucleus and other membrane bound organelles are prokaryotes and include all bacteria. Eukaryotes, on the other hand, have these structures and include plant and animal cells. The origin of eukaryotes (eukaryogenesis) is a major evolutionary transition in the history of life. How can eukaryogenesis and the pathways that lead to and from the prokaryote/eukaryote transition be reconstructed when fossil records are lacking? This project aims to look for the imprints left by this process at the structural and molecular levels across the diversity of modern-day eukaryotes. Such "structural fossils" exist in a protein assembly that defines the prokaryotic cell: the nuclear pore complex (NPC). By dissecting the NPC architecture of a unicellular eukaryote, Trypanosoma brucei, and comparing it to the available structures from other divergent species, the project expects to unravel the molecular processes that governed the evolution of the nucleus. The results should represent a compelling, modern context for teaching and disseminating fundamental concepts in structure and function relationships, molecular evolution and engineering principles of biological systems. Collaboration with the Rockefeller Science Outreach Program will make educational material to discuss evolution available to students and teachers. In addition, this program also engages high school and undergraduate students to work at Rockefeller University. The structures of two of the main T. brucei NPC building blocks, the outer ring complex and the mRNA export platform, will be solved by using an integrative approach that involves: (i) gathering a diverse set of experimental data, including electron microscopy, cross-linking and mass spectrometry and quantitative proteomics: (ii) translation of the resulting data into spatial restraints that are used to calculate the structure of the assembly; and finally, (iii) a detailed comparative analysis of the NPC core components and architecture, covering representative organisms across the eukaryotic lineage. Among the expected outcomes are: to expand the repertoire of membrane coating modules that were involved in the origin of the NPC; to identify new types of membrane coating modules combinations and interfaces and to define how a nucleic acid transport/remodeling machine was appended to a membrane coating module.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.

缺乏内部结构如细胞核和其他膜结合细胞器的单细胞生物是原核生物，包括所有细菌。另一方面，真核生物具有这些结构，包括植物和动物细胞。真核生物的起源（真核发生）是生命史上一个重要的进化转变。在缺乏化石记录的情况下，如何重建真核生物的发生和原核生物/真核生物转变的途径？该项目旨在寻找这一过程在现代真核生物多样性的结构和分子水平上留下的印记。这种“结构化石”存在于定义原核细胞的蛋白质组装中：核孔复合物（NPC）。通过解剖单细胞真核生物布氏锥虫（Trypanosoma brucei）的NPC结构，并将其与其他不同物种的可用结构进行比较，该项目有望解开控制细胞核进化的分子过程。研究结果应代表一个令人信服的，现代的教学和传播的结构和功能关系，分子进化和生物系统的工程原理的基本概念的背景下。与洛克菲勒科学推广计划的合作将使学生和教师获得讨论进化论的教育材料。此外，该计划还吸引高中和本科生在洛克菲勒大学工作。对两种主要的T.布氏鼻咽癌的构建模块，外环复合物和mRNA输出平台，将通过使用综合方法解决，包括：（i）收集不同的实验数据集，包括电子显微镜，交联和质谱和定量蛋白质组学：（ii）将所得数据转化为用于计算组装结构的空间限制;最后，（iii）NPC核心组件和架构的详细比较分析，涵盖了真核生物谱系中的代表性生物。预期的结果包括：扩大参与NPC起源的膜涂层模块的库;识别新型的膜涂覆模块组合和界面，并定义核酸如何运输/该奖项反映了NSF的法定使命，并通过使用基金会的智力价值进行评估，被认为值得支持和更广泛的影响审查标准。