Development of a novel in situ sequencing technique for mapping of genes, circuits, and repair in the human brain

The translation of experimental findings in neuroscience, from advanced human cell systems (in vitro and in vivo) to and from the clinic, is still a significant hurdle.

Place, phenotype, and connectivity are critical to the understanding of brain neural circuitry but challenging to assess together.

What we are working towards here is to develop a novel sequencing approach, called Lock-seq, that achieves spatial details on a sub-micrometer scale but provides the throughput and economics to map thousands of genes in each brain section. The Lock-seq technology will open up for a new way to map gene expression patterns in single brain tissue sections.

Our goal is to develop a technique that is usable on human tissue as well as in complex chimeric models, such as “humanized” mice, human organoids, and in experiments using transplants of human ESC-derived cells.

The long-term goal of this project is to develop a set of innovative tools that will be combined into a new method of gene-transfer connectomics. The approach is based on the transfer of molecular address labels (barcodes) between neurons across synapses.

It provides detailed information on the location of neurons, their connectivity, and the identity of their synaptic partners.With this approach, we aim to dissect the functional changes occurring in the human brain with epilepsy and to deepen our understanding of nerve cell development and maturation in stem cell-based restorative therapies for Parkinson’s disease.