Writing Kilobytes of Images into Living Cells over Time

Biological data must currently be gathered either by observing a cell or cellular system in real time or by extracting a part of that cell or system for destructive analysis. These requirements inherently limit our ability to understand the dynamics of a system as it develops through time. Genomic DNA is an excellent archival data storage medium for biological information. New information can be written and stored in the genome of a living cell by adding or modifying nucleotides. If coupled to biological processes or external events, this information can comprise data, permanently stored in the genome and stably passed down during cell division. The CRISPR-Cas system stores the nucleotide content of invading viruses to confer adaptive immunity. We recently showed that we can harness the CRISPR-Cas system to encode information beyond its native biological purpose (Shipman et al., Science, 2016). In fact, we can encode information in multiple modalities over time, written into the genomes of bacteria and recalled via sequencing. We now move beyond the initial proof-of-concept to scale up this molecular recording system. Here we use the CRISPR-Cas system to encode images and a short movie into the genomes of living bacteria. In doing so, we push the technical limits of this information storage system and test optimized strategies to minimize those limitations. We additionally uncover underlying principles of the CRISPR-Cas adaptation system, including sequence determinants of spacer acquisition relevant for understanding both the basic biology of bacterial adaptation as well as its technological applications. This work demonstrates that practical amounts of real data can be captured and stored in the genome of living cells and later recovered by sequencing – an approach that we intend to apply to the study of cell fate acquisition during neurodevelopment.