CAREER: Biomechanical Signatures in Vertebrate Embryonic Development

这项学院早期职业发展(Career)基金将研究脊椎动物胚胎的关键发育阶段。具体地说，将使用一种新的生物力学方法来定量评估组织和器官的形成。绘制胚胎发育过程中细胞和组织的特征图一直是生物学领域感兴趣的一个广泛话题。目前分析组织生长的方法是侵入性的，要么损害组织，要么具有潜在的毒性。本研究将安全地观察活体胚体的形成。具体地说，这项工作将生成斑马鱼胚胎在生长过程中的三维僵硬图。在脊椎动物中，功能组织和器官的形成过程非常保守。因此，从斑马鱼胚胎中获得的知识也适用于人类胚胎。更好地了解胚胎结构发育将促进发育生物学和生物医学科学的研究。这项工作的结果最终可能使监测人类胚胎发育成为可能，并有助于公众健康。这项研究将通过设计和开发低成本的自己动手的机器人系统，将这项研究整合到PI的教育工作中，这些系统可以很容易地进行修改，并在K-12学校使用。本研究旨在获得健康斑马鱼胚胎和异常斑马鱼胚胎弹性模量的时空分辨率、全身3D图，用于定量描述斑马鱼胚胎的生长和病理。主要有三个目标：(1)通过综合机械压痕、高分辨率三维光学显微镜和有限元方法获得全身三维弹性模量图。(2)通过与分子分析的相关性研究，验证胚胎发育过程中的时空硬度测量是一个重要的生物标志物。(3)评估组织压痕对胚胎发育的影响，证明组织压痕可以在不影响生长的情况下安全地进行。这项研究将通过胚胎发育的无标记、原位、生物力学表征来推进组织表型鉴定的方法学。这种方法比目前的方法更有优势，例如基于组织学的组织表型和基因组分析，这些方法不直接量化机械性能。生物力学表征方法将被用来研究胚胎发育过程中的体细胞发生，这是由间充质向上皮转变(MET)的过程，MET是贯穿组织和器官发育的最基本的细胞过程之一。生物力学方法可以很容易地用于量化其他已知涉及僵硬变化的细胞和组织过程。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This Faculty Early Career Development (CAREER) grant will study key developmental stages of vertebrate embryos. Specifically, a novel biomechanical method will be used to quantitatively assess how tissues and organs form. Mapping the characteristics of cells and tissues during embryonic development has been a broad topic of interest in biology. Current methods to analyze tissue growth are invasive and either damage tissue or are potentially toxic. This study will observe the formation of live embryonic bodies safely. Specifically, the work will generate a 3-dimensional stiffness map of zebrafish embryos during their growth. The process of functional tissue and organ formation is well conserved among vertebrates. Therefore, the knowledge obtained from zebrafish embryos is applicable to human embryos. A better understanding of embryonic structural development will promote studies in developmental biology and biomedical sciences. The results of this work may ultimately enable monitoring of embryo development in humans and contribute to public health. This research will be integrated into the PI's educational efforts through the design and development of low-cost, do-it-yourself robotic systems, which can be easily modified and used in K-12 schools. This research aims to obtain a spatiotemporally-resolved, whole-body 3D map of the elastic modulus of healthy and abnormal zebrafish embryos, which will be used to quantitatively profile their growth and pathology. Three aims will be pursued: (1) Obtain a whole-body 3D elastic modulus map via integrated mechanical indentation, high-resolution 3D light microscopy, and finite element methods. (2) Validate the spatiotemporal stiffness measurement during embryonic development as a significant biomarker through correlation studies with molecular analysis. (3) Assess the effect of tissue indentation on embryonic development to prove that the tissue indentation can be conducted safely without perturbing growth. The study will advance a methodology of tissue phenotyping through the label-free, in situ, biomechanical characterization of embryonic development. This approach offers advantages over current methods, such as histology-based tissue phenotyping and genomic analysis, which do not directly quantify the mechanical properties. The biomechanical characterization method will be used to study somitogenesis during embryonic development, which is governed by the mesenchymal to epithelial transition (MET), one of the most fundamental cellular processes throughout tissue and organ development. The biomechanical method can be easily adapted to quantify other cellular and tissue processes that are known to involve stiffness changes.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.