Recording complex biological signals is a crucial application of synthetic biology, essential for a deeper understanding of biological processes. An ideal “biorecorder” would have the ability to record biological signals over a wide spatial distribution of cells with high temporal resolution. However, the biorecording tools available currently rely on transcription and translation of the biorecorder upon induction of the biological signal making their fastest temporal resolution ~20 minutes. Here we introduce a DNA polymerase based biorecorder that can record cationic concentration fluctuations at a 10-minute time-scale with a resolution of ~1 minute. We use a template independent DNA polymerase; terminal deoxynucleotidyl transferase (TdT) to convert temporal cation concentration changes into incorporated nucleotide preference changes. We first show how the dNTP incorporation preferences change upon addition of the cation to a TdT catalyzed extension reaction. Next we calculate the step-response time of the recording system. We tested three different times of cation addition: 10 minutes, 20 minutes and 45 minutes for a 60 minute experiment and by analyzing the DNA sequences obtained we were able to get time predictions of 11, 21.9 and 44.5 minutes with a standard deviation of 1, 1.9 and 1.4 minutes respectively. As an initial proof of concept for this recorder we record the time course of a modulated cation onto DNA as well. We finally present a prototype for such a recorder that could be used for neural signal recording using simple protein engineering strategies.

Storing temporal data with minutes resolution into DNA

2019 Spring National Meeting

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