CAREER: Biomechanical Signatures in Vertebrate Embryonic Development

职业：脊椎动物胚胎发育中的生物力学特征

• 批准号: 1942518
• 负责人: Kazunori Hoshino
• 金额: $ 50万
• 依托单位: University of Connecticut
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1942518&HistoricalAwards=false
• 关键词: CAREER; Biomechanical; Signatures; Vertebrate; Embryonic

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.

该学院早期职业发展（CAREER）资助将研究脊椎动物胚胎的关键发育阶段。具体来说，一种新的生物力学方法将用于定量评估组织和器官的形成。 在胚胎发育期间绘制细胞和组织的特征一直是生物学中感兴趣的广泛主题。目前分析组织生长的方法是侵入性的，并且损伤组织或具有潜在毒性。本研究将安全地观察活胚体的形成。具体来说，这项工作将生成斑马鱼胚胎在生长过程中的三维刚度图。功能组织和器官形成的过程在脊椎动物中是很保守的。 因此，从斑马鱼胚胎中获得的知识适用于人类胚胎。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。 这项工作的结果可能最终能够监测人类胚胎发育，并有助于公共卫生。这项研究将通过设计和开发低成本、自己动手的机器人系统，融入PI的教育工作中，这些系统可以很容易地在K-12学校进行修改和使用。 本研究旨在获得健康和异常斑马鱼胚胎弹性模量的时空分辨的全身3D地图，该地图将用于定量描述其生长和病理。将追求三个目标：（1）通过集成的机械压痕、高分辨率3D光学显微镜和有限元方法获得全身3D弹性模量图。(2)通过与分子分析的相关性研究，证实胚胎发育过程中的时空刚度测量是一种重要的生物标志物。(3)评估组织压痕对胚胎发育的影响，以证明组织压痕可以安全地进行而不会干扰生长。该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的方法学。这种方法提供了优于当前方法的优势，例如基于组织学的组织表型分析和基因组分析，这些方法不直接量化机械性能。生物力学表征方法将用于研究胚胎发育期间的体节发生，这是由间充质到上皮转化（MET）控制的，这是整个组织和器官发育中最基本的细胞过程之一。该生物力学方法可以很容易地适用于量化其他细胞和组织的过程，已知涉及刚度changes.This奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。