CAREER: In-Vivo Analysis of Active Mechanical Mechanisms Driving Animal Morphegenesis

职业：驱动动物形态发生的主动机械机制的体内分析

• 批准号: 2047140
• 负责人: Sebastian Streichan
• 金额: $ 89.46万
• 依托单位: University of California-Santa Barbara
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2047140&HistoricalAwards=false
• 关键词: CAREER; Vivo; Analysis; Active; Mechanical

How embryos and organs get in shape remains a fundamental and open question. Some of the most common birth defects are associated with irregular shaped organs, underscoring how important form is for proper function. Research in the last century revealed how biochemical processes regulate cell fate, setting the stage for morphogenesis: the question of how genes instruct form. This project will bring concepts from physics that lead the way to a predictive understanding of how complex organs get their shape. The project will provide quantitative understanding of tissue properties, forming the pillar for systematically exploring novel control strategies that force tissue into a prescribed form. The PI will create three dimensional videos of organismal development and disseminate them through a planetarium-like setting to the public. It will also be accessible to many primary and secondary schools, as well as museums.The central goal of this project is to study how active thin sheets remodel to generate 3D form. High-resolution deep tissue imaging in living embryos will be used to uncover active processes and their interplay with bulk material in organ folding. The PI will introduce new techniques such as MKID-FRET to study force analysis at the interface of interacting tissue layers and use optogenetics to precisely manipulate cell activity in space and time to investigate regulatory parameters that govern cellular interplay in shaping tissues. Combined with genetic manipulations, the experiments will be used to uncover the physical mechanisms of how 3D shape is dynamically encoded by 2D gene expression patterns.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.

胚胎和器官如何成形仍然是一个基本而开放的问题。一些最常见的出生缺陷与不规则形状的器官有关，强调了形状对正常功能的重要性。上个世纪的研究揭示了生物化学过程如何调节细胞命运，为形态发生奠定了基础：基因如何指导形态的问题。这个项目将带来物理学的概念，引导人们对复杂器官如何获得形状的预测性理解。该项目将提供对组织特性的定量理解，形成系统地探索迫使组织进入规定形式的新控制策略的支柱。PI将制作生物发育的三维视频，并通过类似天文馆的设置向公众传播。这个项目的中心目标是研究如何将活动的薄片重塑成3D形式。活体胚胎中的高分辨率深层组织成像将用于揭示活跃的过程及其与器官折叠中大块材料的相互作用。PI将引入新技术，如MKID-FRET，以研究相互作用的组织层界面处的力分析，并使用光遗传学在空间和时间上精确操纵细胞活性，以研究控制组织成形中细胞相互作用的调控参数。结合基因操作，这些实验将用于揭示三维形状如何由二维基因表达模式动态编码的物理机制。该奖项反映了NSF的法定使命，并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，被认为值得支持。