(335c) Engineering a DNA Polymerase to Become a Calcium-Sensitive Biosensor/Recording Device

DNA is an excellent information medium. This is proven not only by biological history, but recent advances in which modern DNA reading and writing technologies have successfully utilized the four-base code as a substitute for the 1’s and 0’s of binary. The next frontier of this technology is to engineer a device that harnesses the information capacity of DNA to record data in real-time. Application in biological contexts would appear both obvious and advantageous, with the DNA polymerase an ideal signal transducer. Accordingly, if a DNA polymerase were engineered to have a have a functional change in response to an environmental cue, it could function as a “ticker-tape” recorder. Here we apply a rational mutagenesis approach to graft a calmodulin-like calcium binding motif to the exonuclease domain of a DNA polymerase to deliver a step change in fidelity (loss in proof-reading capacity) upon calcium binding. Our hope is for this device to contribute to brain mapping efforts, currently lacking technologies with sufficient space-time measurement resolution, by recording the calcium spikes associated with neuronal firing into DNA.