Our Exploratory Research core includes academic-style basic science projects addressing open questions, and hypothesis- or discovery-driven. Expected outcomes are new biological insights (e.g., pathway, target, mechanism, etc.) or ground-breaking new tools or engineering concepts. The Exploratory Research core will be expanding over the next months.
We use single-cell genomic, imaging, and stem cell bioengineering technologies to explore human development and disease. Broadly, we like to think about how cell fates and states are established during organ formation, how diverse cells organise themselves in complex microenvironments, and how disrupted cell ecosystems lead to disease. We use and develop high-information content measurements and computational methods to explore these topics. Currently we work primarily on development and disorders of the central nervous system and gastrointestinal tract. We are also interested in how human organs are different from other species, and how human evolution has led to disease susceptibilities.
The development of CRISPR-mediated gene engineering has greatly expanded the scope and ease of generating accurate disease models. Yet, implementation of these tools in adult stem cell-derived organoids has proven to be technically challenging. The Organoid Gene Editing group develops new strategies to overcome existing technological bottlenecks and automate workflows. We employ next-generation CRISPR tools to generate complex isogenic disease models and confer synthetic features to organoids. These engineered organoids enable us to study cell fate specification in different epithelial tissues, as well as to explore the biology of rare intestinal cell types such as enteroendocrine cells.