Recording the developmental plasticity of a mammalian brain in DNA tapes

The chart of synaptic connections within a mammalian brain will serve as a reference map for generations, rivaling the impact of reference genomes. However, such maps have been elusive because current microscopy-based methods do not scale and necessitate sample destruction, losing the developmental history of synapses. We propose a novel “DNA tape” system that uses DNA barcodes traveling through synapses to generate a high-resolution synaptic map of the mouse brain. Utilizing the established CRISPR lineage tracing tools from Yachie Lab, the DNA tapes will record developmental histories via targeted base-editors, unveiling the dynamics of synaptic plasticity. Furthermore, we propose trans-splicing to fuse barcodes from different neurons, hereby circumventing the need for single-cell isolation and paving the way for larger dynamic brain maps. This project aims to develop a pioneering technology to create an open-access mammalian brain connectivity map, significantly enhancing the scale and depth of synaptic plasticity recording.

Faculty Supervisor:

Nozomu Yachie

Student:

Partner:

Osaka University

Discipline:

Life Sciences

Sector:

Education

University:

The University of British Columbia

Program: