The blood-brain barrier (BBB) protects the brain and is essential for proper neuronal function, but it also poses a major obstacle to drug delivery to the brain. Natasha O’Brown’s lab studies how the BBB forms during development, maintains function throughout life, and fails in disease. By leveraging the zebrafish model system, her team combines live imaging with high-throughput in vivo genetic and chemical screens to identify the signals that regulate barrier integrity over time. Their work aims to define how the BBB is shaped by its cellular environment and how these interactions break down in neurodegeneration.