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

在胚胎发育过程中，细胞群（称为“集体”）一起移动，以帮助形成组织和器官。这些细胞团在发育中的胚胎中的运动尚不清楚。该奖学金将研究果蝇作为模型系统的发展，以了解细胞集体如何在活的完整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镜方法来揭示集体如何在组织中移动，并利用光来控制细胞运动。PI和一名博士后研究员将在圣巴巴拉的加州大学接受这些新技术的培训，然后将这些技术带回家乡机构（堪萨斯州立大学）。这些研究将产生新的工具，可用于研究胚胎如何发育成完全形成的动物，并提高我们对细胞集体如何在组织内移动的更广泛的理解。技术说明多细胞群体或细胞集体的迁移对器官发生过程中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，但人们还不清楚细胞是如何保持有序和迁移的，尽管它们在密集的组织中移动。果蝇的边缘细胞是一个很好的遗传学模型系统，以解决如何细胞集体的物理和分子与天然组织环境的相互作用。该奖学金的目标是通过使用边缘细胞系统的尖端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的研究人员合作进行，该大学是集体细胞迁移和创新活细胞操作和成像领域的领导者。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的组合，这些工具将在宿主研究中心使用，这些工具采用光来操纵活细胞中的蛋白质功能。这些技术将解决：（1）组织形状和组织如何影响边缘细胞集体迁移;（2）Rap 1，一种关键的信号蛋白，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的理解。PI将在PI上介绍并推广这项技术的采用？他的家乡机构，堪萨斯州立大学（KSU）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。

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.