We engineer synthetic cellular memory platforms that enable the reconstruction of cellular histories and can be applied as living diagnostics.
A fundamental challenge in biology is to understand how cells function and integrate complex molecular information to perform different behaviors. For example, the differentiation of a stem cell into two daughter cells with distinct identities or the transformation of a normal cell into a cancer cell. This challenge has motivated the creation of numerous technologies facilitating detailed intracellular observations at the level of DNA, RNA, protein, and metabolites. Despite the power of these approaches, they generally require destructive methods and therefore observations are limited to a few snapshots in time or select asynchronous cellular processes. One provocative solution to this is to introduce DNA writing and molecular recording platforms within cells that enable the encoding, storage, and retrieval of molecular information.
Towards the goal of continuously recording molecular events within cells, my laboratory is developing and applying Record-seq, a ‘transcriptional recording’ platform that employs CRISPR spacer acquisition from RNA to capture and convert intracellular RNAs into DNA, permanently storing transcriptional information in the DNA of living cells. The newly acquired sequences serve as transcriptional records, which are retrievable via deep sequencing and can be leverage to reconstruct cellular histories. This technology provides an entirely new mode of interrogating dynamic biological and physiological processes and opens up numerous avenues for future work in engineering cellular systems.