Collaborative Research: Uncovering the Biophysical Mechanisms of Single-cell Wound-healing
合作研究:揭示单细胞伤口愈合的生物物理机制
基本信息
- 批准号:1938109
- 负责人:
- 金额:$ 56.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-03-01 至 2024-02-29
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Creating systems that confer life-like properties has been a major endeavor in both science and engineering. Recent years have witnessed an explosion in research on building synthetic cells, not only as a way to study the origins and the rules of life, but also as a new approach to biochemical engineering to increase the yield in making molecules. Nevertheless, current synthetic cell research has neglected one of the most fundamental properties of living matter – the ability to self-repair following damage. Living cells are generally soft and easily damaged, yet a number of them can repair themselves after being mechanically punctured, torn, or even ripped in half. If one could construct such self-repairing capability in synthetic cells, it should be possible to gain insights into one of the defining features of cells. At the same time, it could open new realms of biochemical engineering by allowing the synthetic cell systems to operate robustly under the potentially harsh environment of industrial processes. One approach to attaining self-repairing synthetic cells is to adapt self-repair mechanisms from a living system which already demonstrates robust capacity to heal from large mechanical wounds within a single cell, and build analogs of these mechanisms inside synthetic cells. One such system is Stentor coeruleus, a single-celled free-living ciliate, which possess a more robust wound healing capacity than most other cells. However, the self-repair mechanisms of Stentor are largely unknown. The overall goal of this proposal, therefore, is to understand the mechanisms by which Stentor cells can heal robustly from large mechanical wounds. The results of this work will lead to fundamental insights into wound healing, one of the defining features of life. It will also lay the foundation for constructing self-repairing synthetic cells. The collaboration between the researchers will provide a unique opportunity for training and workforce development at the interface of cell biology and engineering. A website on “superhero cells and bugs” will be created to raise public interest in non-model organisms possessing “superpowers” such as self-healing and survival in space. The researchers will continue their efforts to recruit underrepresented minorities to science and engineering via social media, outreach activities targeted to K-12 students, and their active participation in the Bay Area Science Festival and the Maker Faire.The overall goal of this research is to understand at a physical and molecular level how Stentor coeruleus cells can heal robustly from large mechanical wounds that cause an opening in the plasma membrane. The key biological questions probed include: What sets the limit of the biggest wound the cell can recover from? Does the large size of the cell facilitate its wound healing, or has wound healing evolved to be particularly rapid in this cell? The rationale to focus on Stentor are: 1) its wound healing capacity is more robust than most other cells, capable of recovering from drastic wounds and regenerating from cell fragments as small as 1/27th of original cell size in 24 hours. 2) The ability to perform high-throughput gene knockdown and wounding experiments. The research objectives are to: 1) Develop a minimalistic whole-cell mathematical model of single-cell wound healing. 2) Test predictions of the model by measuring the kinetics of healing in cells as a function of wound size and cell size. 3) Identify contributions to the healing process from membrane patching, purse-string constriction, or other mechanisms as identified by phosphoproteomics. The intellectual merit of this research lies in the identification of the principles for repairing large mechanical wounds in a single cell, and the conditions at which the healing process will succeed or fail. Fundamentally, the ability to heal is one of the key features that distinguish living matter from non-living matter. This study will shed light into the problem of how some biological systems can heal more robustly than others. Practically, the work will lay the foundation for engineering a new function—self-repair—in synthetic cells, and will make the technology more robust for potential scale-up for practical industrial applications.This award was co-funded by the Cellular Dynamics and Function and Systems and Synthetic Biology clusters of the Division of Molecular and Cellular Biosciences.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.
创造赋予生命特性的系统一直是科学和工程领域的一项重大奋进。近年来,构建合成细胞的研究出现了爆炸式增长,不仅是研究生命起源和规则的一种方式,也是生物化学工程的一种新方法,以提高分子制造的产量。然而,目前的合成细胞研究忽略了生命物质最基本的特性之一-损伤后自我修复的能力。活细胞通常是柔软的,容易受损,但其中一些细胞在被机械刺穿,撕裂,甚至撕成两半后可以自我修复。如果人们能够在合成细胞中构建这种自我修复能力,那么就有可能深入了解细胞的一个定义特征。与此同时,它可以通过允许合成细胞系统在工业过程的潜在恶劣环境下稳健地运行来开辟生物化学工程的新领域。获得自我修复合成细胞的一种方法是从已经表现出强大的能力的生命系统中调整自我修复机制,以从单个细胞内的大型机械伤口中愈合,并在合成细胞内构建这些机制的类似物。一个这样的系统是Stentor coeruleus,一种单细胞自由生活的纤毛虫,它比大多数其他细胞具有更强大的伤口愈合能力。然而,Stentor的自我修复机制在很大程度上是未知的。因此,本提案的总体目标是了解Stentor细胞可以从大型机械伤口中稳健愈合的机制。这项工作的结果将导致对伤口愈合的基本见解,生命的定义特征之一。它还将为构建自我修复的合成细胞奠定基础。研究人员之间的合作将为细胞生物学和工程学接口的培训和劳动力发展提供独特的机会。将建立一个关于“超级英雄细胞和虫子”的网站,以提高公众对具有“超级能力”的非模式生物的兴趣,如自我修复和在太空中生存。研究人员将继续努力,通过社交媒体,针对K-12学生的外展活动,这项研究的总体目标是在物理和分子水平上了解Stentor coeruleus细胞如何从导致血浆开放的大型机械伤口中强劲愈合膜的所探讨的关键生物学问题包括:是什么限制了细胞可以恢复的最大创伤?细胞的大尺寸是否促进了伤口愈合,或者伤口愈合在这种细胞中进化得特别快?专注于Stentor的理由是:1)其伤口愈合能力比大多数其他细胞更强大,能够在24小时内从严重伤口中恢复并从原始细胞大小的1/27的细胞碎片中再生。2)进行高通量基因敲除和创伤实验的能力。本研究的主要目的是:1)建立一个单细胞创伤愈合的最小化全细胞数学模型。2)通过测量作为伤口大小和细胞大小的函数的细胞愈合动力学来测试模型的预测。3)确定膜修补,荷包收缩或磷酸蛋白质组学确定的其他机制对愈合过程的贡献。这项研究的智力价值在于确定了在单个细胞中修复大型机械伤口的原则,以及愈合过程成功或失败的条件。从根本上说,治愈的能力是区分生命物质和非生命物质的关键特征之一。这项研究将揭示一些生物系统如何比其他系统更强大地愈合的问题。实际上,这项工作将为在合成细胞中设计一种新的功能--自我修复奠定基础,并将使该技术更强大的潜在规模扩大的实际工业应用。这个奖项是共同的,该奖项由分子和细胞生物科学部的细胞动力学和功能以及系统和合成生物学集群资助。该奖项反映了NSF的法定使命,并被认为值得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。
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Aurora kinase inhibitors delay regeneration in Stentor coeruleus at an intermediate step.
极光激酶抑制剂在中间步骤延迟了蓝斑鱼的再生。
- DOI:
- 发表时间:2020
- 期刊:
- 影响因子:0
- 作者:Lin,Athena;Summers,Diana;Reiff,SarahB;Tipton,AaronR;Tang,SindyK;Marshall,WallaceF
- 通讯作者:Marshall,WallaceF
Hydrodynamic dissection of Stentor coeruleus in a microfluidic cross junction
- DOI:10.1039/d2lc00527a
- 发表时间:2022-08-08
- 期刊:
- 影响因子:6.1
- 作者:Paul,Rajorshi;Zhang,Kevin S.;Tang,Sindy K. Y.
- 通讯作者:Tang,Sindy K. Y.
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Sindy KY Tang其他文献
Sindy KY Tang的其他文献
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{{ truncateString('Sindy KY Tang', 18)}}的其他基金
Collaborative Research: Biomechanical mechanisms conferring wound resilience in single-celled organisms
合作研究:赋予单细胞生物伤口复原力的生物力学机制
- 批准号:
2317442 - 财政年份:2023
- 资助金额:
$ 56.87万 - 项目类别:
Standard Grant
NSF2026: EAGER: Material morphogenesis using biohybrid vesicles as building blocks
NSF2026:EAGER:使用生物混合囊泡作为构建块的材料形态发生
- 批准号:
2033387 - 财政年份:2021
- 资助金额:
$ 56.87万 - 项目类别:
Standard Grant
RAPID: Effective mass spray disinfection using Unmanned Aerial Vehicles (UAVs)
RAPID:使用无人机(UAV)进行有效的大规模喷雾消毒
- 批准号:
2030390 - 财政年份:2020
- 资助金额:
$ 56.87万 - 项目类别:
Standard Grant
Collaborative Research: Bottom-up Construction of a Synthetic Neuron and Programmable Neuronal Network
合作研究:合成神经元和可编程神经元网络的自下而上构建
- 批准号:
1935315 - 财政年份:2019
- 资助金额:
$ 56.87万 - 项目类别:
Standard Grant
Collaborative Research: Investigation of Wound-healing at the Single Cell Level using Microfluidics-based Microsurgery
合作研究:使用基于微流体的显微外科技术研究单细胞水平的伤口愈合
- 批准号:
1517089 - 财政年份:2015
- 资助金额:
$ 56.87万 - 项目类别:
Standard Grant
CAREER: Interrogating and Exploiting the Hydrodynamics of Concentrated Emulsions for Droplet Microfluidics
职业:探究和利用浓缩乳液的流体动力学用于液滴微流体
- 批准号:
1454542 - 财政年份:2015
- 资助金额:
$ 56.87万 - 项目类别:
Continuing Grant
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