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

University Of California-Santa Barbara, Santa Barbara CA

Investigators

Abstract

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.