Contractility and apoptosis in germline architecture and oogenesis

所有生物都是由细胞组成的，但大多数细胞都非常微小，而且排列紧密，如果没有强大的放大倍数，就无法分辨。相比之下，动物的卵是非常大的细胞;鸟类的卵是单个巨大的细胞。所有的动物都是用一个精心制作的细胞（生殖细胞）来产生卵子的，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，例如研究人员使用的动物，生殖细胞就像一条传送带;随着它们的生长，隔室及其内容物从生殖细胞的一端转移到另一端。目前尚不清楚这些隔间如何保持彼此之间的联系，以及这些联系如何随着隔间的扩大和成熟而变化。本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（包括人类卵）都利用了这一过程的某种形式。此外，这项工作将为本科生、研究生和博士后研究人员沿着高中教师提供培训机会。额外的推广工作将把科学带入当地的小学。研究人员使用秀丽隐杆线虫作为模型动物。该项目将利用该系统中广泛的遗传学，并采用最先进的活显微镜成像方法来观察和测量生殖细胞室动态。对于沿着种系沿着不同位置的隔室，以及随着隔室的出生、死亡或扩大，研究人员将比较隔室的大小及其与共享的中央核心相关的“门道”。他们还比较了隔间墙壁和门口的各种细胞成分的数量，重点关注传递生化信息或重新排列以产生力量的球员。并非所有的隔室最终都成为卵母细胞;有些隔室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，他们将通过模拟和生物实验进行测试。研究和推广活动的执行将确定细胞结构和卵子生产的机制，加强科学研究潜力，并在资助期间和未来几代人中增加研究多样性。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。

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.