Spindle Self-Organization and Bioenergetics in Vivo

目前还没有一个既定的框架能够理解细胞器的结构和行为，细胞器是细胞内的专门结构，可以包含数百万个动态的、能量传递的分子。同样，细胞代谢极其复杂，涉及数百种蛋白质、复杂的网络和众多的中间代谢化合物，目前我们缺乏通过不同途径预测通量的能力。这个项目采用了物理学中用于研究复杂系统的范式，将定量实验与唯象理论相结合，但应用这些方法来研究纺锤体、卵母细胞生物能量学以及两者之间的相互作用。这项工作将提供对细胞分裂和能量新陈代谢的基本见解，并有助于为理解生命物质的非平衡热力学铺平道路。该项目的目标是对纺锤体、能量代谢以及两者之间的相互作用有一个定量的了解。所获得的知识将有助于解释代谢缺陷是如何扰乱细胞分裂和细胞骨架组织的，这被认为会导致多种病理，包括癌症、神经疾病和不孕不育。此外，如果对生物、活性物质的非平衡热力学有足够的了解，最终将有可能设计出具有逼真特性的人造活性材料。研究生、本科生和高中生将通过项目工作以及课堂、暑期课程和教程，接受跨学科研究方面的培训。将大力加强妇女和任职人数不足的少数群体对这些活动的参与。所取得的成果将在研究期刊、实验室网站和会议(包括新的跨学科会议)上传播。PI将每月举办一系列关于科学交流的活动，帮助研究生和博士后掌握宝贵的技能，并加强他们对公共宣传的参与。这将包括与高中教师、作家、企业家和艺术家的合作，并将有助于创建一个热衷于科学交流的人的社区。新陈代谢提供了持续的能量流动，决定了许多亚细胞结构的形式和功能。这些亚细胞结构是活性物质，由使用化学能执行机械功的分子组成，局部破坏详细的平衡。这种自组织结构最引人注目的例子之一是纺锤体，它在细胞分裂期间分离染色体。尽管它发挥着核心作用，但人们对纺锤体等活跃的亚细胞物质的非平衡热力学知之甚少。在这个项目中，PI将使用定量实验和理论相结合的方法来研究小鼠卵母细胞纺锤体行为和生物能量学之间的相互作用。该项目的目标是为了解和预测纺锤体的行为和体内的能量代谢，以及一个扰动如何影响另一个提供系统的基础。这项工作还旨在通过对活的、活动的物质的非平衡热力学的定量研究来为物理学做出贡献。这一奖项反映了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。

There is no established framework capable of understanding the structure and behaviors of organelles, specialized structures within a cell that can contain millions of dynamic, energy-transducing molecules. Similarly, cellular metabolism is extremely complex, involving hundreds of proteins, intricate networks, and numerous intermediate metabolic compounds, and we currently lack the ability to predict the flux through different pathways. This project employs the paradigm used to study complex systems in physics of integrating quantitative experiments with phenomenological theories, but applies these methods to study the spindle, oocyte bioenergetics, and the interactions between the two. This work will provide fundamental insight into cell division and energy metabolism, and will help pave the way towards an understanding of the nonequilibrium thermodynamics of living matter. The goal of the project is to develop a quantitative understanding of the spindle, energy metabolism, and the interaction between the two. The knowledge gained will help explain how metabolic defects disrupt cell division and cytoskeletal organization, which is believed to cause diverse pathologies, including cancer, neurological diseases, and infertility. Furthermore, if the nonequilibrium thermodynamics of living, active matter become sufficiently well understood, it will eventually become possible to engineer manmade active materials with lifelike properties. Graduate students, undergraduates, and high school students will be trained in interdisciplinary research, both through working on the project, and in classes, summer courses, and tutorials. A strong effort will be taken to enhance the involvement of women and underrepresented minorities in these activities. The results obtained, will be disseminated in research journals, on the lab web site, and at conferences (including new, interdisciplinary conferences). The PI will create a monthly series of events on scientific communication that will help give graduate students and postdocs valuable skills and enhance their engagement with public outreach. These will include collaborations with high school teachers, writers, entrepreneurs and artists, and will help create a community of people who are passionate about scientific communication.Life is a nonequilibrium phenomenon. Metabolism provides a continuous flux of energy that dictates the form and function of many subcellular structures. These subcellular structures are active materials, composed of molecules which use chemical energy to perform mechanical work and locally violate detailed balance. One of the most dramatic examples of such a self-organizing structure is the spindle, which segregates chromosomes during cell division. Despite its central role, very little is known about the nonequilibrium thermodynamics of active subcellular matter, such as the spindle. In this project the PI will study the interplay between spindle behaviors and bioenergetics in mouse oocytes using a combination of quantitative experiments and theory. The goal of this project is to provide a systematic basis to understand and predict the behaviors of the spindle and energy metabolism in vivo, and how perturbing one impacts the other. This work also aims to contribute to physics through the quantitative study of the nonequilibrium thermodynamics of living, active matter.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.