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RoL: Coordination of collective cell migration in complex tissues

RoL：复杂组织中集体细胞迁移的协调

基本信息

批准号：
2027617
负责人：
Jocelyn McDonald
金额：
$ 93.89万
依托单位：
Kansas State University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2027617&HistoricalAwards=false
关键词：
RoL Coordination collective cell migration

项目摘要

The development of animals requires the movement of cells to create and shape tissues and organs in the embryo. Cells often cooperate with each other by moving as a united group, but how this works is unclear. This research uses the simple fruit fly model, along with genetics and live cell imaging, to probe how groups of cells come together, adapt their shapes, and move as one within a whole tissue. This project will define the way that cells move together in the tissues and organs of many animals. A broader impact will be the recruitment of college students from underrepresented groups to perform in-depth research. Workshops for 6th-8th grade and 9th-12th grade girls will use a low-cost ‘build your own’ microscope (the Foldscope) to learn about nature and science. Lastly, engineering students will design and make a device to alter the tissue and find out the impact on how cell groups move. These activities will help students get excited about biology and inspire them to become scientists or engineers.Movement is a fundamental property of life, that crosses many levels, from molecules to cells and tissues to organisms. Cell migration is fundamental to how diverse tissues and organs form and are remodeled during animal embryonic development. Migrating cells must sense, respond, and adapt to changes in the immediate tissue environment. Cells that move collectively are further challenged to stay together, communicate, respond, and adapt cooperatively as multicellular units to tissue-scale forces and signals. An integrated understanding of the mechanisms that keep cell collectives moving inside tissues is lacking. The proposed studies will fill this knowledge gap by elucidating the dynamic molecular, cytoskeletal, organellar, cellular, and tissue-level mechanisms that promote collective cell motility in complex environments. Specifically, this project uses the Drosophila border cell collective because it is a tractable model amenable to real-time live cell imaging, genetic tools, and optogenetic cellular manipulation, all within the native developing tissue. Building on previous studies, this project will uncover: (1) how the critical signaling nexus Rap1 coordinates adhesion and the cytoskeleton to keep border cells moving inside the developing tissue; (2) how nuclear deformation, along with connections to the cellular cytoskeleton, helps border cells adapt to changes in the tissue microenvironment and morphology; (3) how alterations in gene expression facilitate movement inside crowded tissues. These studies will uncover conserved mechanisms that drive and regulate collective cell movement within tissues, thus linking principles of cooperativity and adaptability in the movement of cell nuclei, single cells, collectives, tissues, and animals as a whole.This research award is funded by the Developmental Systems, Cellular Dynamics and Function, and Rules of Life Programs, all within the Biological Sciences Directorate.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.

动物的发育需要细胞的运动来创造和塑造胚胎中的组织和器官。细胞经常以一个统一的群体的方式相互合作，但这是如何工作的还不清楚。这项研究使用简单的果蝇模型，结合遗传学和活细胞成像，来探索细胞群是如何聚集在一起，适应它们的形状，并在整个组织中作为一个整体移动的。这个项目将定义细胞在许多动物的组织和器官中一起运动的方式。更广泛的影响将是从代表性不足的群体中招募大学生进行深入研究。为6 -8年级和9 -12年级的女孩开设的讲习班将使用一种低成本的“自己建造”显微镜（折叠显微镜）来学习自然和科学。最后，工科学生将设计并制造一个设备来改变组织，并找出对细胞群如何移动的影响。这些活动将帮助学生对生物学产生兴趣，并激励他们成为科学家或工程师。运动是生命的基本属性，它跨越了许多层面，从分子到细胞，从组织到生物体。在动物胚胎发育过程中，细胞迁移是多种组织和器官形成和重塑的基础。迁移细胞必须感知、响应和适应直接组织环境的变化。作为多细胞单位，集体移动的细胞进一步面临着保持在一起、交流、反应和合作适应组织规模的力量和信号的挑战。对保持细胞集体在组织内运动的机制缺乏一个完整的理解。提出的研究将通过阐明在复杂环境中促进集体细胞运动的动态分子、细胞骨架、细胞器、细胞和组织水平机制来填补这一知识空白。具体来说，这个项目使用了果蝇边界细胞群，因为它是一个易于处理的模型，适合实时活细胞成像、遗传工具和光遗传细胞操作，所有这些都在原生发育组织中。在以往研究的基础上，本项目将揭示：(1)关键信号纽带Rap1如何协调粘附和细胞骨架，以保持边缘细胞在发育组织内的移动；(2)核变形以及与细胞骨架的连接如何帮助边缘细胞适应组织微环境和形态的变化；(3)基因表达的改变如何促进拥挤组织内的运动。这些研究将揭示驱动和调节组织内集体细胞运动的保守机制，从而将细胞核、单个细胞、集体、组织和动物整体运动中的协同性和适应性原则联系起来。该研究奖由生物科学理事会下属的发育系统、细胞动力学和功能以及生命规则项目资助。该奖项反映了美国国家科学基金会的法定使命，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。