Spindle Flux and Mechanics

主轴磁通和力学

• 批准号: 2134215
• 负责人: Jennifer Ross
• 金额: $ 108.27万
• 依托单位: Syracuse University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2134215&HistoricalAwards=false
• 关键词: Spindle; Flux; Mechanics

Cells are the fundamental unit of life and all cells arise by cell division. To ensure that each daughter cell receives a complete set of the instructions for life, cells first duplicate their genetic material (DNA) and then move one copy to each daughter cell. Cells perform this task millions of times each day. The machine utilized for cell division is called the mitotic spindle. The mitotic spindle is required to organize and arrange the chromosomal DNA and segregate it into the daughter cells. This process is extremely important for the formation, development and maintenance of all living organisms. The self-organization of the mitotic spindle cannot be understood using biology alone. Rather, it requires the understanding of the underlying physical principles that govern the assembly and function of the mitotic spindle. The research conducted here will apply physical concepts behind self-organization of liquid crystals (the same liquid crystals found in computer and cell phone screens) to understand the ability of the mitotic spindle to organize itself in the absence of outside instructions. Understanding the fundamental rules of life that underlie cellular organization will result in new knowledge about how cells work as well as new insights to help us understand and ultimately fight diseases. The project will involve outreach to 8th and 9th grade girls in the nearby community, along with interdisciplinary training of undergraduates and graduate students.The scientific objective of this proposal is to understand how microtubule turnover and crosslinking control the organization and dynamics of the mitotic spindle. The mitotic spindle is a high-density organization of cross-linked microtubules which should be enough to stall the inherent microtubule dynamic instability as well as the mobility of the filaments within the structure. Yet, it has been shown that the spindle undergoes overall flux from the chromosomes toward the poles. This flux has been noted to be faster at the chromosomes than at the poles. A new model put forth by the investigators proposes that the flux is an essential process to fluidize the spindle near chromosomes where enhanced motion is needed to error correction. Flux decreases at the poles because of increased adhesion due to higher levels of crosslinkers put there by the process of flux. This exciting new model creates a new physical framework to begin exploring the underlying fundamental principles that enable the dynamic self-organization of the mitotic spindle. The proposed work will directly test the hypothesized model using quantitative light microscopy and genetic manipulations. These tests will reveal new information on the inner workings of the spindle. The proposal directly responds to several important aspects of modern biological research including integrating across scales, from single molecules to complex structures and whole cells. The active matter experiments directly address the synthesis of life-like systems using minimal purified components. From a physics perspective, the synthesis of life-like systems are essential to understanding the non-equilibrium processes of biology that couple to self-organize, sense, and respond to stimuli. This is a frontier area of physics and materials research, which will uncover new knowledge about fundamental cell biology.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.

细胞是生命的基本单位，所有细胞都是通过细胞分裂产生的。为了确保每个子细胞接收到一套完整的生命指令，细胞首先复制它们的遗传物质（DNA），然后将一个拷贝转移到每个子细胞。 细胞每天执行这个任务数百万次。用于细胞分裂的机器称为有丝分裂纺锤体。有丝分裂纺锤体需要组织和排列染色体DNA并将其分离到子细胞中。这一过程对所有生物体的形成、发育和维持都极为重要。有丝分裂纺锤体的自我组织不能单独使用生物学来理解。相反，它需要了解的基本物理原理，管理有丝分裂纺锤体的组装和功能。在这里进行的研究将应用液晶自组织背后的物理概念（与计算机和手机屏幕中发现的液晶相同）来理解有丝分裂纺锤体在没有外部指令的情况下组织自己的能力。了解细胞组织的基本生命规则将导致关于细胞如何工作的新知识，以及帮助我们理解并最终对抗疾病的新见解。 该项目将涉及向附近社区的八年级和九年级女生进行外展，沿着对本科生和研究生进行跨学科培训。本提案的科学目标是了解微管周转和交联如何控制有丝分裂纺锤体的组织和动力学。有丝分裂纺锤体是交联微管的高密度组织，其应足以阻止固有的微管动力学不稳定性以及结构内细丝的流动性。然而，已经表明，纺锤体经历了从染色体到两极的整体通量。这种通量在染色体上比在两极上更快。研究人员提出的一个新模型提出，通量是使纺锤体靠近染色体的必要过程，在染色体附近需要增强运动来纠错。焊剂在两极处减少，因为焊剂过程中产生的较高水平的交联剂增加了粘附力。这个令人兴奋的新模型创建了一个新的物理框架，开始探索使有丝分裂纺锤体动态自组织的基本原则。拟议的工作将直接测试使用定量光学显微镜和遗传操作的假设模型。这些测试将揭示主轴内部工作的新信息。该提案直接回应了现代生物学研究的几个重要方面，包括从单分子到复杂结构和整个细胞的跨尺度整合。活性物质实验直接解决了使用最少的纯化成分合成类生命系统的问题。从物理学的角度来看，类生命系统的合成对于理解生物学的非平衡过程至关重要，这些过程与自组织，感知和对刺激的反应相结合。这是物理和材料研究的前沿领域，将揭示基础细胞生物学的新知识。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。

项目成果

The multifunctional spindle midzone in vertebrate cells at a glance

脊椎动物细胞中的多功能纺锤体中区一目了然

• DOI: 10.1242/jcs.250001
• 发表时间: 2021
• 期刊: Journal of Cell Science
• 影响因子: 4
• 作者: Wadsworth, Patricia

Self-Assembly of Microtubule Tactoids

• DOI: 10.3791/63952
• 发表时间: 2022-06-01
• 期刊: JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
• 影响因子: 1.2
• 作者: Chauhan，Prashali;Sahu，Sumon;Ross，Jennifer L.
• 通讯作者: Ross，Jennifer L.