The systems developmental biology of zebrafish body elongation

斑马鱼身体伸长的系统发育生物学

基本信息

批准号：
10552318
负责人：
SCOTT A HOLLEY
金额：
$ 63.23万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-01 至 2027-12-31
项目状态：
未结题

项目摘要

This research program focuses on the systems developmental biology, biophysics and biomechanics of early spinal column development. The research program utilizes zebrafish as model for understanding the mechanisms of human development and causes of birth defects such as scoliosis and spina bifida. The experimental approach is driven by the idea that quantitative in vivo analysis will lead to fundamental insights into the emergence of biological organization from the collective interaction of its constituent parts. The research program combines genetics, embryology, in vivo biophysics, live imaging and systems level data analysis and computational modeling to study pattern formation and morphogenesis. The proposed research program will address a number of questions regarding biological order and the reproducibility of embryonic development. The program will follow-up on the lab’s recent finding that a dynamically stable pattern of cell state transitions underlies the reproducibility of development to understand the mechanisms maintaining dynamic stability during zebrafish body elongation. The research program will also examine the mechanism of mechanical information regulating the flux of cells through a developmental trajectory. The program will address how tissue-tissue interactions constrain cell behavior during body elongation. At the molecular and cellular level, the program will utilize newly developed methods for in vivo single molecule biophysics to study cell adhesion protein dynamics and their relation to cell state transitions and cell morphology. Overall, this is multi-scale research program that considers the roles of molecules, cells and tissues in the genesis of order in the developing embryo.

该研究计划的重点是系统发展生物学，生物物理学和早期脊柱发育的生物力学。该研究计划将斑马鱼用作了解人类发展机制和出生缺陷的原因的模型例如脊柱侧弯和脊柱裂。实验方法是由这样的想法驱动的定量体内分析将导致对生物学出现的基本见解组织的集体互动构成部分。研究计划结合遗传学，胚胎学，体内生物物理学，实时成像和系统级别数据分析以及研究模式形成和形态发生的计算模型。提议研究计划将解决有关生物秩序和胚胎发育的可重复性。该计划将在实验室最近的发现中进行跟进动态稳定的细胞状态过渡模式是繁殖的基础开发以了解保持斑马鱼体内动态稳定性的机制伸长。研究计划还将检查机械信息的机制通过发育轨迹调节细胞的通量。该计划将解决如何组织 - 组织相互作用限制了身体伸长过程中的细胞行为。在分子和细胞水平，该程序将利用新开发的体内单分子的方法生物物理学研究细胞粘附蛋白动力学及其与细胞态过渡的关系细胞形态。总体而言，这是多尺度研究计划，它考虑了发育中的胚胎中有序的生成中的分子，细胞和组织。