The intestinal tract plays a crucial role in development, regeneration, immunity, and nutrition. Despite their relevance, many critical aspects of intestinal development and function remain unexplored. In our laboratory, we take a multidisciplinary approach to better understand the molecular mechanisms involved in intestinal morphogenesis, patterning, and metabolism during homeostasis. We utilize organotypic cell models as basic systems and mouse epithelial tissues as more physiological models for our investigations. Additionally, we have initiated a new research line using mouse embryonic stem cells (mESC) to address epithelial lumen formation and asymmetric division during development.
Our goal is to understand the mechanisms that coordinate tissue architecture, such as epithelial cell polarity, oriented cell divisions, and lumen formation in the early embryo, as well as in tubular organs like the embryonic neural tube and forming gut. We also aim to comprehend the processes that break symmetry in the early embryo and forming organs. 3D organoids offer unprecedented opportunities to directly address these questions by monitoring cell and tissue behavior in vivo.
Objectives:
- Establish primary lines of human and mice embryonic stem cells for in vitro use to assemble next-generation organoids -NGO- (Gatruloids, Neuruloids, and Gutoids).
- Identify culture conditions for growing NGO in organ-on-a-chip technology systems with microfluidics.
- Identify novel regulators of organoid polarity through protein interaction mapping approaches (proximity labelling) and genetic screens.
- Validate candidate components in vivo through localization studies (live cell imaging using fluorescent proteins).
To address our research questions, we utilize high-resolution 3D imaging to quantitatively characterize engineered organoids’ cellular behavior, incorporating fluorescence reporters and/or immunolabeling.
