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

胚胎和器官是如何形成的仍然是一个基本的悬而未决的问题。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。这个项目将引入物理学的概念，引导人们对复杂器官如何形成形状的预测性理解。该项目将提供对组织特性的定量理解，为系统探索迫使组织形成规定形式的新型控制策略奠定基础。PI将制作有机发展的三维视频，并通过类似天文馆的设置向公众传播。许多中小学和博物馆也可以进入。该项目的中心目标是研究活动薄板如何重新建模以生成3D形状。活体胚胎的高分辨率深层组织成像将用于揭示活跃过程及其与器官折叠中大块物质的相互作用。PI将引入MKID-FRET等新技术来研究相互作用组织层界面的力分析，并使用光遗传学精确地操纵空间和时间上的细胞活动，以研究控制细胞相互作用形成组织的调节参数。结合基因操作，实验将用于揭示三维形状如何被二维基因表达模式动态编码的物理机制。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.