Editing the Developing Brain: from in utero CRISPR knockins to broadly-accessible personalized patient models

How do brain circuits form? What instructs self-assembly of connectivity during development, and how is input from the environment used later in life? How does circuitry emerge from cell biology, and what goes wrong in mental illness and pathologies of brain wiring? Might we be able to ameliorate miswiring in patients? To get at these questions, our team develops synthetic biology tools and applies them to the developing brain of mice and rats. A big focus is developing new CRISPR tools able to knock in precise genome edits directly in the developing bran, often by in utero electroporation, to track and manipulate neural circuits and their molecules as the brain develops. With these approaches, are investigating the wiring patterns that underlie conditions on the neurodevelopmental spectrum, including, epilepsy, autism, and schizophrenia. The goal of our group is to understand the in vivo mechanisms that determine circuit formation in development and circuit remodeling in adulthood; to discover how these processes deviate to alter brain circuits in neurodevelopmental conditions and mental illness; and to develop the knowhow and methodologies that may allow therapeutic intervention for the regeneration of circuits lost to disease or trauma.