RII Track-4: Dynamic Live Imaging and Manipulation of Migrating Collectives Inside Tissues

非技术描述：在胚胎发育过程中，细胞群（称为“集体”）一起移动，帮助形成组织和器官。这些集体在发育中的胚胎内的运动尚不清楚。该奖学金将研究果蝇的发展作为一个模型系统，以了解细胞集体如何在活的，完整的组织内移动，并与之相互作用。该项目的科学目标是使用新的先进显微方法来揭示组织中的集体运动，并利用光来控制细胞运动。PI和一名博士后将在加州大学圣巴巴拉分校接受这些新技术的培训，然后将这些技术带回家乡（堪萨斯州立大学）。这些研究将产生新的工具，可以用来研究胚胎如何发育成完全形成的动物，并提高我们对组织内细胞集体如何运动的更广泛的理解。技术描述在器官发生过程中，多细胞群或细胞群的迁移对组织的形成和重组至关重要。虽然集体迁移是发育所必需的，但细胞如何在密集排列的组织内移动却保持有序和迁移尚不清楚。果蝇边界细胞是一个极好的遗传可处理的模型系统，用于解决细胞集体如何在物理和分子上与原生组织环境相互作用。该研究的目标是通过使用前沿的边界细胞系统活细胞成像来揭示迁移集体和组织之间相互作用的机制。这项工作将与加州大学圣巴巴拉分校的研究人员合作进行，该大学在集体细胞迁移和创新活细胞操作和成像领域处于领先地位。PI将采用选择性平面照明（SPIM）光片荧光显微镜（LSFM），体内生物传感器和光遗传学工具（利用光来操纵活细胞中的蛋白质功能）的组合，将在宿主位点使用。这些技术将解决：(1)组织形状和组织如何影响边界细胞集体迁移；(2) Rap1是一种关键的信号蛋白，它如何控制边缘细胞在组织内迁移过程中的粘附强度和动力学。该项目将允许PI创建和使用创新的成像和光遗传学工具，以大大推进我们对细胞集体如何在复杂的原生环境中迁移的概念和机制理解。PI将在PI上介绍和推广该技术的采用？通过培训其他研究人员如何使用生物传感器和光遗传学工具来帮助美国堪萨斯州立大学（KSU）。

Nontechnical Description:During the development of embryos, groups of cells (referred to as 'collectives') move together to help form tissues and organs. Movement of these collectives inside the developing embryo is poorly understood. This fellowship will study development of the fruit fly as a model system to understand how cell collectives move within, and interact with, living, intact tissues. The scientific goals of this project are to use new advanced microscopic methods to reveal how collectives move in tissues, and to use light to control cell movements. The PI and a postdoctoral fellow will be trained in these new techniques at the University of California, Santa Barbara, and will then bring the techniques back to the home institution (Kansas State University). These studies will result in new tools that can be used to study how embryos develop into fully formed animals, and to improve our broader understanding of how cell collectives move within tissues.Technical DescriptionThe migration of multicellular groups, or cell collectives, is vital to the formation and reorganization of tissues during organogenesis. While collective migrations are required for development, it is not well understood how cells stay ordered and migratory despite moving inside densely packed tissues. Drosophila border cells are an excellent genetically tractable model system to address how cell collectives physically and molecularly interact with the native tissue environment. The goal of this fellowship is to uncover mechanisms that underlie interactions between migrating collectives and tissues through the use of cutting-edge live cell imaging of the border cell system. The work will be performed in partnership with reasearchers at the University of California, Santa Barbara, which is a leader in the field of collective cell migration and innovative live cell manipulation and imaging. The PI will employ a combination of Selective Plane Illumination (SPIM) light sheet fluorescent microscopy (LSFM), in vivo biosensors, and optogenetic tools that employ light to manipulate protein function in live cells, will be used at the host site. These techniques will address: (1) how tissue shape and organization impacts border cell collective migration; and (2) how Rap1, a key signaling protein, controls the adhesion strength and dynamics of border cells during their migration inside the tissue. The project will allow the PI to create and use innovative imaging and optogenetic tools to considerably advance our conceptual and mechanistic understanding of how cell collectives migrate in complex native environments. The PI will introduce and promote adoption of this technology at the PI?s home institution, Kansas State University (KSU) by training other investigators on how to use biosensors and optogenetic tools.