COLLABORATIVE RESEARCH: Building the Contractile Ring in the Early Embryo

合作研究：在早期胚胎中构建收缩环

• 批准号: 1917983
• 负责人: Charles Shuster
• 金额: $ 90万
• 依托单位: New Mexico State University
• 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=1917983&HistoricalAwards=false
• 关键词: COLLABORATIVE; RESEARCH; Building; Contractile; Ring

The process of dividing one cell into two - termed cytokinesis - is fundamental to all life on Earth and this project seeks to further elucidate the structure and function of the protein-based machinery that mediates the splitting of the cell. The machinery that accomplishes animal cell cytokinesis is known as the contractile ring and it consists of a transiently assembled belt of cytoskeletal proteins which generates the force required to divide the cell. Employing a variety of imaging technologies in combination with computational modeling, this project will test the hypothesis that in animal cells the contractile ring assembles from nodes of contractile proteins that aggregate into a functional contractile assemblage. The resulting increase in knowledge of the architecture and dynamics of the contractile ring derived from this project will have significant impacts on research in the fields of cell proliferation, movement, shape change, as well as differentiation and development. This project will train students from a four-year liberal arts college (Dickinson College) and a minority-serving research university (New Mexico State University), who will work not only at their respective institutions but also collaboratively at the University of Washington's Friday Harbor Laboratories (FHL). A computational modeler with experience in agent-based modeling of cytoskeletal protein dynamics will provide training in agent-based modeling. Lastly, the investigators will engage in a number of activities that will broaden the impact of the project through the broadening of participation of URM students, the integration of research and education, and public engagement and improvement of science literacy.The aims of this project will test the hypothesis that the contractile ring assembles from nodes comprised of the cytoskeletal proteins myosin II, actin, septins and anillin, which then congress into a mature contractile machine that generates the force necessary for cytokinesis. This node-based mode of ring assembly occurs in fission yeast, but had never been demonstrated in higher order animals cells until the investigators described the presence of node-like structures in the early contractile rings of sea urchin embryos. Using this report as a foundation, the investigators will apply super resolution, electron, and live cell microscopy to examine node composition, assembly and aggregation during cytokinesis in sea urchin and sea star embryos. Using empirical data as well as existing models for yeast node congression, two- and three-dimensional, agent-based models will be tested in silico, and results from these simulations will be used to inform further experimentation. Lastly, these approaches will be applied to the study of polar lobe formation, which uses a contractile ring-like structure that forms during cytokinesis in many early embryos, but whose composition and spatiotemporal regulation may be quite different from a standard contractile ring.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.

将一个细胞分成两个的过程-称为胞质分裂-是地球上所有生命的基础，该项目旨在进一步阐明介导细胞分裂的蛋白质机制的结构和功能。 完成动物细胞胞质分裂的机制被称为收缩环，它由细胞骨架蛋白质的瞬时组装带组成，其产生分裂细胞所需的力。 该项目采用各种成像技术与计算建模相结合，将测试以下假设：在动物细胞中，收缩环由收缩蛋白的节点组装而成，这些收缩蛋白聚集成功能性收缩组合。由此增加的知识的结构和动力学的收缩环来自这个项目将有显着的影响，在细胞增殖，运动，形状变化，以及分化和发展领域的研究。该项目将培训来自四年制文理学院（迪金森学院）和少数民族服务研究型大学（新墨西哥州州立大学）的学生，他们不仅将在各自的机构工作，还将在华盛顿大学的星期五港实验室（FHL）合作。具有基于代理的细胞骨架蛋白质动力学建模经验的计算建模师将提供基于代理的建模培训。最后，研究人员将参与一系列活动，通过扩大URM学生的参与，整合研究和教育，公众参与和提高科学素养来扩大该项目的影响。该项目的目的将测试收缩环由细胞骨架蛋白肌球蛋白II，肌动蛋白，septins和苯胺组成的节点组装的假设，然后，它会进入一个成熟的收缩机器，产生胞质分裂所需的力量。这种基于节点的环组装模式发生在裂变酵母中，但从未在高等动物细胞中得到证实，直到研究人员描述了海胆胚胎早期收缩环中存在节点样结构。以这份报告为基础，研究人员将应用超分辨率，电子和活细胞显微镜检查海胆和海星星胚胎胞质分裂过程中的节点组成，组装和聚集。使用经验数据以及现有的酵母节点大会模型，将在计算机上测试基于代理的二维和三维模型，这些模拟的结果将用于通知进一步的实验。最后，这些方法将应用于极叶形成的研究，极叶形成使用许多早期胚胎在胞质分裂期间形成的收缩环状结构，但其组成和时空调节可能与标准的收缩环有很大不同。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。