Michael Ratz

The human genome contains several thousand genes that encode the brain’s connectome, a precise assembly of neural connections with trillions of synapses. How is genomic information translated into synapse-specific connectivity underlying behavior and cognition? Answering this fundamental question will provide important insights about the general principles underlying nervous system development and is relevant for human disease. Here I propose to develop a novel approach based on genetic barcoding and single-cell Spatial Transcriptomics that permits a comprehensive understanding about neural network assembly via the large-scale measurement of molecular, cellular, and circuit-level mechanisms in the mouse brain. Compared to current efforts that require vast scientific resources to map synaptic connectivity among a few cells or small tissue volumes, my approach will enable routine measurements of neural connections among thousands of cells with molecular detail using standard laboratory equipment. I will systematically reveal the connectivity rules underlying the spatiotemporal development of neural circuits from diverse cell types in the mouse cortex and employ CRISPR perturbations to engineer neural circuitry in vivo. My work will provide an innovative experimental platform and reveal mechanistic insights into the developmental algorithms that the genome uses to encode the connectome.