Grant: Project Grant

Recent advances in developmental organoids offer new opportunities to understand the fundamental mechanisms of tissue pattern formation and growth during early human development. This emerging knowledge will underpin innovative approaches in the early detection, prevention, and ultimately treatments of developmental diseases. Furthermore, developmental organoids act as a foundational model system for a variety of organoid types, offering key design principles that advance a broad spectrum of translational applications. Unfortunately, current technologies face limitations due to poor robustness and reproducibility, alongside an incomplete understanding of the controllable parameters that influence growth and cellular pattern formation. Here, we propose an integrated experimental and computational project to uncover the design principles and control parameters in developmental organoids. To do this, we will apply a design, test and learn framework to three dimensional gastruloids, pluripotent-stem-cell derived organoids capable of mimicking peri-gastrulation like events such as the emergence of the three-germ layers and the formation of the body plan. We will utilize multiplex microfabricated platforms, magnetic micro-beads and cell engineering to learn how morphogen position, strength and duration influence the morphology of stem cell-derived aggregates. Our experimental data will lay the groundwork for creating a comprehensive multi-scale computational framework. We hypothesize this framework will allow us to quantify, infer, and predict multi-cellular behavior, guiding controlled organoid development with unprecedented precision and robustness. The applicability of this framework to other organoids will be tested, offering new insights into developmental processes and advancing in-vitro systems for disease modeling and drug testing.