Grant: CIHR Fellowship

As an organism develops, simple homogenous tissues undergo successive patterning and morphogenetic events to produce structurally complex heterogenous organs. In vertebrates, these events are primarily driven by reciprocal morphogen and mechanical signals between two or more adjacent cell types. Despite extensive knowledge about the individual nature of the signals and cell types involved, however, less is known about how they come together to create large-scale patterns, sharp boundaries, and the final size and shape of tissues-especially in the context of human development. A marked example of this is the development of the human gut, where despite the ability to create and study human cell types for almost every region in vitro, we still lack basic knowledge about how the embryonic gut tube regionalizes and sets the sites of the future endodermal organs. Such knowledge is not only critical for understanding development, but also for understanding and potentially treating a variety of common congenital disorders. It would also be greatly beneficial for tissue engineers for deriving new strategies to create tissues and organs for regenerative medicine. With a Life Sciences Research Foundation Fellowship, I plan to build on recent progress combining tools from synthetic biology with human embryonic stem cells to create a novel model system for studying the patterning and morphogenesis of the human gut. The system will also be applicable more generally to studying other instances of tubular patterning during human development, and for experimenting with and creating synthetic organ systems for future clinical application.