Reconstructing the cellular history of developing neurons using molecular recordings

  • Awarded: 2019
  • Award Type: Bridge to Independence
  • Award #: 549763

The widespread use of genome sequencing has provided the research community with an incredible, new opportunity to determine the root causes of autism by uncovering genes that are mutated across many individuals with the disorder. However, these identified genes and mutations themselves do not tell us which cells or, critically, at what point in time the developing brain may be affected. To better focus our investigations into the cell biology of these potentially pathogenic mutations, we need a more robust understanding of the early cell fate decisions and organizing events in the developing brain. Unfortunately, to date, we have been held back in this pursuit because of technical limitations. Traditional techniques in experimental cell biology require either direct observation or destructive analysis of the cells being studied. This is problematic when studying a complex, developing system such as the brain.

To circumvent this limitation, Seth Shipman’s laboratory is taking a new approach: the logging of biological events as coded nucleotides, written into the genome of a living cell using CRISPR-integrase based technology1,2. These organized changes to genomic DNA enable the storage of data during an event of interest, without interrupting the ongoing biological processes that is then collected later by sequencing. Using this new type of molecular data collection, known as ‘molecular recordings,’ Shipman’s team plans to probe the developing brain in a different dimension and build out a more complete framework of the system. These studies will provide a framework to guide future investigations into how ASD-linked mutations alter brain development.


1.Shipman S.L. et al. Science 353, aaf1175 (2016) PubMed
2.Shipman S.L. et al. Nature 547, 345-349 (2017) PubMed
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