CAREER: Imaging Cellular Dynamics with Nanometer Resolution
职业:以纳米分辨率成像细胞动力学
基本信息
- 批准号:1832100
- 负责人:
- 金额:$ 71.89万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-06-30 至 2023-03-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The major goal of this research is to contribute to our mechanistic understanding of how cells communicate with each other and the outside environment. Communication among cells is critical for most, if not all, living systems and regulates processes including cell migration, cell division, growth, and death. One way this occurs is though a process called endocytosis whereby molecules are transported into the cell. Endocytosis requires an intricate coordination of proteins inside the cell as well as physical changes to the surface of the cell. The deformation of the cell's surface is central to endocytosis, yet there are few tools that can dissect these physical changes that are necessary for endocytosis. One reason this is difficult to study is that this processes is dynamic and occurs on the nanoscale, beyond the resolution of traditional microscopy. This project will advance the study of nanometer scale cell surface dynamics by developing and applying new methods to measure and manipulate the process of endocytosis in living cells. Many biological processes occur on this scale, and the methods developed in this research will be widely applicable across a range of biological systems including virus entry and budding, cell migration, and neurobiology. In addition to contributing to understanding cellular processes, the effort will include training students from K-12 through graduate school on microscopy and the value of multi-disciplinary approaches in understanding cellular processes. The goal of this research is to understand the dynamics of endocytic vesicle assembly and the interconnected roles played by the proteins involved, as well as the physical changes to plasma membrane shape. A recently developed fluorescence microscopy technique is uniquely suited to imaging nanometer dynamics of vesicle formation in real-time in living cells. In Aim 1 the novel microscopy technique is used to measure endocytic pit formation dynamics upon stimulation with EGF. This experimental platform will then be used to dissect the protein dynamics during pit formation, mapping the correlation between protein dynamics and plasma membrane morphology (Aim 2). Finally, a strategy will be developed to physically stall endocytosis utilizing a tethered ligand. This platform will be used to explore curvature sensing and curvature inducing proteins (Aim 3). This research will yield a quantitative description of ligand internalization dynamics and the interplay between protein recruitment and membrane morphology on a millisecond time scale. Completion of this research will shed light on previously undiscovered mechanisms of plasma membrane dynamics and signaling that may revolutionize the way cellular communication is understood. Further, it will provide new tools to broadly improve the understanding of plasma membrane dynamics in cell signaling and homeostasis. In addition to providing K-12 though graduate students with a rich educational experience, the PI will make available to the community any software that is produced and which is useful to others in achieving high resolution data.This award is supported jointly by the Division of Molecular and Cellular Biosciences and the Physics of Living Systems program in the Division of Physics
这项研究的主要目标是有助于我们对细胞如何相互交流和外部环境的机械理解。细胞间的通讯对于大多数(如果不是全部)生命系统至关重要,并调节包括细胞迁移,细胞分裂,生长和死亡在内的过程。发生这种情况的一种方式是通过一个称为内吞作用的过程,分子被运送到细胞中。内吞作用需要细胞内蛋白质的复杂协调以及细胞表面的物理变化。细胞表面的变形是内吞作用的核心,但很少有工具可以剖析这些内吞作用所必需的物理变化。这很难研究的一个原因是,这个过程是动态的,发生在纳米尺度上,超出了传统显微镜的分辨率。本计画将借由开发及应用新方法来量测及操控活细胞内吞过程,进而推动奈米尺度细胞表面动力学的研究。许多生物过程都是在这种规模上发生的,本研究开发的方法将广泛适用于一系列生物系统,包括病毒进入和出芽,细胞迁移和神经生物学。 除了有助于理解细胞过程,这项工作将包括培训学生从K-12通过研究生院显微镜和多学科方法在理解细胞过程的价值。本研究的目的是了解内吞囊泡组装的动力学和相关蛋白质所起的相互作用,以及质膜形状的物理变化。最近开发的荧光显微镜技术是唯一适合于成像纳米动态实时在活细胞中的囊泡形成。在目的1中,使用新的显微镜技术来测量EGF刺激后内吞小凹形成的动力学。然后,该实验平台将用于剖析纹孔形成过程中的蛋白质动力学,绘制蛋白质动力学与质膜形态之间的相关性(目的2)。最后,将开发一种策略,利用拴系配体物理地停止内吞作用。该平台将用于探索曲率传感和曲率诱导蛋白(Aim 3)。这项研究将产生一个定量描述的配体内化动力学和蛋白质招聘和膜形态之间的相互作用在毫秒的时间尺度。这项研究的完成将揭示以前未发现的质膜动力学和信号传导机制,可能会彻底改变细胞通讯的方式被理解。此外,它将提供新的工具,以广泛提高细胞信号和稳态质膜动力学的理解。 除了为K-12的研究生提供丰富的教育经验外,PI还将向社区提供所生产的任何软件,这些软件对其他人在获得高分辨率数据方面有用。该奖项由分子和细胞生物科学部以及物理学部的生命系统物理学项目共同支持。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Alexa Mattheyses其他文献
Determining how Pemphigus Vulgaris Impacts the Nanoscale Architecture of Desmosomes
- DOI:
10.1016/j.bpj.2017.11.2941 - 发表时间:
2018-02-02 - 期刊:
- 影响因子:
- 作者:
Tara Urner;Emily Bartle;Tejeshwar Rao;Andrew Kowalczyk;Alexa Mattheyses - 通讯作者:
Alexa Mattheyses
Cadherin Order and Dynamics in Calcium-Dependent and Independent Desmosomes
- DOI:
10.1016/j.bpj.2017.11.2989 - 发表时间:
2018-02-02 - 期刊:
- 影响因子:
- 作者:
Emily Bartle;Tara Urner;Tejeshwar Rao;Alexa Mattheyses - 通讯作者:
Alexa Mattheyses
Alexa Mattheyses的其他文献
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{{ truncateString('Alexa Mattheyses', 18)}}的其他基金
Developing quantitative understanding of adaptor-clathrin coating at the trans-Golgi network
定量了解跨高尔基体网络的接头网格蛋白涂层
- 批准号:
2126374 - 财政年份:2021
- 资助金额:
$ 71.89万 - 项目类别:
Standard Grant
CAREER: Imaging Cellular Dynamics with Nanometer Resolution
职业:以纳米分辨率成像细胞动力学
- 批准号:
1553344 - 财政年份:2016
- 资助金额:
$ 71.89万 - 项目类别:
Continuing Grant
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