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

胚胎和器官是如何形成形态的，这仍然是一个基本而悬而未决的问题。一些最常见的出生缺陷与形状不规则的器官有关，这突显了形状对正常功能的重要性。上个世纪的研究揭示了生化过程如何调节细胞命运，为形态发生奠定了基础：基因如何指导形成的问题。这个项目将带来来自物理学的概念，这些概念将导致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属性的定量了解，为系统探索迫使组织进入规定形式的新控制策略奠定基础。PI将制作生物体发育的三维视频，并通过天文馆般的环境向公众传播这些视频。这个项目的中心目标是研究如何将活动的薄板重新建模以生成3D形式。活体胚胎的高分辨率深层组织成像将被用来揭示器官折叠中的活跃过程及其与大宗物质的相互作用。PI将引入新技术，如MKID-FRET，研究相互作用组织层界面上的力分析，并使用光遗传学精确操纵细胞在空间和时间上的活动，以研究控制细胞在塑造组织过程中相互作用的调控参数。结合遗传操作，这些实验将被用来揭示3D形状如何由2D基因表达模式动态编码的物理机制。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.