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.
