Contractility and apoptosis in germline architecture and oogenesis

种系结构和卵子发生中的收缩性和细胞凋亡

• 批准号: 2153790
• 负责人: Amy Maddox
• 金额: $ 106.82万
• 依托单位: University of North Carolina at Chapel Hill
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-15 至 2026-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2153790&HistoricalAwards=false
• 关键词: Contractility; apoptosis; germline; architecture; oogenesis

All living things are made of cells, but most cells are so tiny and closely packed that they cannot be resolved without powerful magnification. By contrast, animal eggs are exceptionally large cells; bird eggs are single enormous cells. All animals produce eggs with an elaborate cell (the germline) that has many inter-connected compartments that become eggs. In some animals, such as the one the investigators use, the germline cell operates as a conveyor belt; compartments and their contents are displaced from one end of the germline to the other as they grow. It is not known how the compartments maintain connection with each other, and how these connections change as compartments enlarge and mature. This project will uncover the mechanisms of this process. The Broader Impacts of the project include the intrinsic merit of the work itself as all animal eggs (including those of humans) utilize some form of this process. Additionally, the work will provide training opportunities for undergraduates, graduate students, and post-doctoral researchers along with high school teachers. Additional outreach work will bring science into local gradeschools.The investigators use Caenorhabditis elegans as a model animal. The project will make use of the extensive genetics available in this system and employ state of the art live microscopic imaging approaches to observe and measure germline compartment dynamics. For compartments at different positions along the germline, and as compartments are born, die, or enlarge, the investigators will compare the size of the compartment and its associated “doorway” to the shared central core. They also compare the amount of various cellular components on compartment walls and doorways, focusing on players that convey biochemical information or that rearrange to generate force. Not all compartments ultimately become oocytes; some undergo programmed cell death. The investigators will study the role of this process in germline architecture and oogenesis. Computer modeling will generate testable predictions that they will test with simulations and biological experiments. Execution of the research and the outreach activities will define mechanisms of cell structure and egg production, strengthen scientific research potential, and increase research diversity during the funding period and for generations to come.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.

所有的生物都是由细胞组成的，但大多数细胞都是如此微小和紧密地堆积在一起，如果没有强大的放大技术，它们是无法分解的。相比之下，动物蛋是特别大的细胞；鸟蛋是单一的巨大细胞。所有动物的卵子都有一个精致的细胞(生殖系)，这个细胞有许多相互连接的隔间，这些隔间变成了卵子。在一些动物中，比如研究人员使用的那种动物，生殖系细胞就像传送带一样运作；随着生殖系的生长，隔室及其内容物从生殖系的一端移到另一端。目前尚不清楚这些舱室如何保持彼此的联系，以及随着舱室的扩大和成熟，这些联系如何变化。这个项目将揭示这一过程的机制。该项目的更广泛影响包括工作本身的内在价值，因为所有动物卵子(包括人类的卵子)都利用这一过程的某种形式。此外，这项工作还将为本科生、研究生和博士后研究人员以及高中教师提供培训机会。更多的外展工作将把科学带入当地的年级学校。研究人员使用秀丽线虫作为模型动物。该项目将利用该系统中可用的广泛遗传学，并使用最先进的活显微成像方法来观察和测量生殖系隔室的动态。对于生殖线上不同位置的隔室，随着隔室的出生、死亡或扩大，研究人员将把隔室的大小及其相关的“门口”与共享的中央核心进行比较。他们还比较了隔间墙壁和门口各种细胞成分的数量，重点放在传递生化信息或重新排列以产生力量的玩家身上。并不是所有的隔室最终都会变成卵母细胞；有些会经历程序性细胞死亡。研究人员将研究这一过程在生殖系结构和卵子发生中的作用。计算机建模将产生可测试的预测，他们将用模拟和生物实验进行测试。这项研究和推广活动的实施将确定细胞结构和卵子生产的机制，加强科学研究潜力，并在资助期和未来几代人增加研究多样性。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。