Search for the minimal requirements for sustainable and tunable cell cycles in synthetic cells

寻找合成细胞中可持续和可调节细胞周期的最低要求

• 批准号: 2218083
• 负责人: Qiong Yang
• 金额: $ 108.93万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 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: 2022-06-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2218083&HistoricalAwards=false
• 关键词: Search; minimal; requirements; sustainable; tunable

Almost every living being on Earth has an internal biological clock, known as circadian rhythms, to drive patterns of many important bodily functions, such as sleep-wake cycles in animals. Likewise, all cells rely on another clock, called cell cycles, for precise timing of cell growth and cell division. Although both circadian rhythms and cell cycles have been studied for decades, these biological clocks are themselves complicated networks interacting with other cellular networks to orchestrate various downstream events and are frequently connected to diseases from insomnia to cancer. The complexity of these systems makes it very difficult to isolate the core machinery to understand their minimized requirements. This project aims to make further major advances in the direction of understanding cellular oscillations by reconstituting and investigating minimal cell-cycle clock systems in synthetic cells. The knowledge gained from this research is disseminated to the broader community through publications, conferences, courses, and hands-on demonstrations. The major broader impact activities involve the early exposure of underrepresented students to frontier research and retention of these students in STEM fields. College level students are introduced to the state-of-the-art technology developed in this project. The project also develops and implements outreach programs to disseminate the scientific findings to the broader public through the collaborations with the University of Michigan Museum of National History. Biological oscillators, including the cell cycle, have a significant impact on the ability of organisms to establish morphogenetic patterns in embryos and maintain basic physiology in adults. It is thus crucial to understand the design and function of these biological clocks. Such understanding provides fundamental knowledge of development and guidance to create synthetic oscillators. Despite its importance, the minimized design principles for constructing versatile and resilient oscillators remains elusive. This research combines several strategies to ascertain the essential rules underlying a fundamental out-of-equilibrium process, the mitotic cell cycles. Specifically, the project builds a unique synthetic cell system, using microemulsion droplets, to dissect the circuit-function relation of an in vitro cell-cycle network and uses the knowledge gained to create a minimized cell-cycle network from the bottom up. The synthetic cellular system is composed of the smallest possible sets of proteins, mRNAs, and ATP as the energy source. A successful project will provide significant insights into the minimal requirements of the network topology that is responsible for the desired cell-cycle performance and response to environmental perturbations.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.

几乎地球上的每一个生物都有一个内部的生物钟，称为昼夜节律，以驱动许多重要的身体功能的模式，例如动物的睡眠-觉醒周期。同样，所有细胞都依赖于另一种称为细胞周期的时钟，以精确计时细胞生长和细胞分裂。尽管人们已经对昼夜节律和细胞周期进行了数十年的研究，但这些生物钟本身就是与其他细胞网络相互作用的复杂网络，以协调各种下游事件，并且经常与失眠和癌症等疾病有关。这些系统的复杂性使得很难隔离核心机器以了解其最小化的要求。该项目旨在通过重建和研究合成细胞中的最小细胞周期时钟系统，在理解细胞振荡的方向上取得进一步的重大进展。从这项研究中获得的知识通过出版物，会议，课程和实践演示传播到更广泛的社区。主要的更广泛的影响活动涉及代表性不足的学生早期接触前沿研究和保留这些学生在STEM领域。大学水平的学生介绍了国家的最先进的技术在这个项目中开发。该项目还制定和实施了外展计划，通过与密歇根大学国家历史博物馆的合作，向更广泛的公众传播科学发现。生物振荡器，包括细胞周期，对生物体在胚胎中建立形态发生模式和在成年人中维持基本生理的能力有重大影响。因此，了解这些生物钟的设计和功能至关重要。这种理解提供了开发的基本知识和创建合成振荡器的指导。尽管它的重要性，最小化的设计原则，用于构建多功能和弹性振荡器仍然难以捉摸。这项研究结合了几种策略，以确定基本的失衡过程，有丝分裂细胞周期的基本规则。具体而言，该项目使用微乳液液滴构建了一个独特的合成细胞系统，以剖析体外细胞周期网络的电路功能关系，并使用所获得的知识自下而上创建最小化的细胞周期网络。合成细胞系统由尽可能小的蛋白质、mRNA和作为能量来源的ATP组成。一个成功的项目将为网络拓扑的最低要求提供重要的见解，该网络拓扑负责所需的细胞周期性能和对环境扰动的响应。该奖项反映了NSF的法定使命，并通过使用基金会的智力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

Nuclear-cytoplasmic compartmentalization of cyclin B1-Cdk1 promotes robust timing of mitotic events

• DOI: 10.1016/j.celrep.2022.111870
• 发表时间: 2022-12-27
• 期刊: CELL REPORTS
• 影响因子: 8.8
• 作者: Maryu，Gembu;Yang，Qiong
• 通讯作者: Yang，Qiong

Comprehensive Parameter Space Mapping of Cell Cycle Dynamics under Network Perturbations

• DOI: 10.1021/acssynbio.3c00631
• 发表时间: 2024-02-29
• 期刊: ACS SYNTHETIC BIOLOGY
• 影响因子: 4.7
• 作者: Li，Zhengda;Wang，Shiyuan;Yang，Qiong
• 通讯作者: Yang，Qiong