Multiplex recording of cellular events over time on CRISPR biological tape

Abstract

Although dynamics underlie many biological processes, our ability to robustly and accurately profile time-varying biological signals and regulatory programs remains limited. Here we describe a framework for storing temporal biological information directly in the genomes of a cell population. We developed a "biological tape recorder" in which biological signals trigger intracellular DNA production that is then recorded by the CRISPR-Cas adaptation system. This approach enables stable recording over multiple days and accurate reconstruction of temporal and lineage information by sequencing CRISPR arrays. We further demonstrate a multiplexing strategy to simultaneously record the temporal availability of three metabolites (copper, trehalose, and fucose) in the environment of a cell population over time. This work enables the temporal measurement of dynamic cellular states and environmental changes and suggests new applications for chronicling biological events on a large scale.

Synthetic biology—Engineering nature to make materials

“…In this way, Harris Wang at Columbia University in New York and colleagues made E. coli that could record the ephemeral availability of different metabolites in their environment over time. 13 …”

CRISPR hack transforms cells into data recorders

“…Synthetic biologist Harris Wang of Columbia University Medical Center in New York City has been developing systems that he hopes to use to study microbes in the gut 5 .…”

DNA writing at a single genomic site enables lineage tracing and analog recording in mammalian cells

“…This paradigm of DNA recording has recently seen a transformation with the development of geneticallyencoded CRISPR-based systems that drive rapid mutational accumulation at neutral loci in a cell's genome [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] . When the activity of such systems is linked to the presence of an arbitrary biological stimulus, accumulated mutations become a record of the strength and duration of exposure to the stimulus 3,5,7 ; and when activity is constitutive, accumulated mutations capture lineage relationships among individual cells 2,[4][5][6][11][12][13][14] . Two recent architectures for CRISPR-based recording systems are particularly amenable to recording in extremely large numbers of mammalian cells.…”