Bacteria as living hard disks

Synthetic biologists store analog information in the genome of cells

Programmable cells perform logical operations, but their results can usually only be stored as digital data. Researchers have now found a way to store analog information – information about the strength or duration of an environmental stimulus, for example. Targeted mutations in the genome preserve the information over long periods of time. This means that all the basic capabilities of a computer can now be reproduced in living cells.

The core function of a computer is based on the input, processing and output of data. Biologists have long been able to reproduce these processes in living cells: synthetic circuits have mastered almost all logical operations necessary for data processing. But computers also need a powerful memory to develop their full potential. However, synthetic biologists have not yet found a satisfactory solution for this function.

Bacteria as living hard disks

Illustration: christine daniloff

The DNA of the genetic material is an ideal storage medium: flexible, durable and easy to duplicate. But until now, mostly only digital information could be kept – whether a cell was exposed to a stimulus or not. Researchers fahim farzadfard and timothy lu of the U.S. Massachusetts institute of technology have now taken an important step forward (farzadfard and lu, science 2014: genomically encoded analog memory with precise in vivo DNA writing in living populations): they were also able to record analog information – how strong the stimulus was or how long it lasted.

Their method is also comparatively simple. It is based on natural genetic elements called retrons: two short DNA strands and an enzyme form a functional unit that can rewrite the genetic material at defined locations. The researchers now coupled a retron to synthetic circuits that respond to environmental stimuli: if the stimulus was successful, permanent mutations in the genome were the result. They named this method SCRIBE: synthetic cellular recorders integrating biological events.

A simple trick allows to log the strength of the stimulus. SCRIBE does not change every cell: only a small fraction of bacteria exposed to a stimulus also accumulate mutations in their genome. But the mutation rate always remains predictable – the stronger or more persistent the stimulus, the more cells are altered. Thus, the fraction of mutated cells allows conclusions to be drawn about the core sizes of the stimulus.

The first experiments with chemical substances were successful: the concentration of the chemicals could be reliably estimated from the proportion of mutated cells. The duration of a stimulus was also measurable. A SCRIBE module activated by illumination was able to reliably record how long bacteria were exposed to a light source. And this even when the light was switched off and on again for longer periods in between.

The memory function also proved to be long-lasting: the results remained stored in the genome for at least 12 days – the equivalent of about 120 bacterial generations. The researchers were even able to insert different SCRIBE modules into the same cells and thus determine two chemical stimuli simultaneously. Two modules are not the end point: in principle, an almost arbitrary number of independent circuits can be assigned their own memory function.

In addition, there are different ways to read out the memory. The simplest variant is to couple a SCRIBE module with a color reaction. The option of sequencing the entire genome of the bacteria is much more complex. However, the information content is also significantly higher: many different SCRIBE modules could be analyzed simultaneously.

There is no shortage of conceivable practical applications. SCRIBE enables the development of environmental sensors that record changes easily and cost-effectively. This includes humans: modified bacteria could colonize the gut and document the absorption of nutrients. Also love to monitor the course of an intestinal infection. This offered medicine new diagnostic tools that are not feasible with electronic sensors.

The SCRIBE method is a simple, efficient and expandable data storage system for living systems. Cells were thus able to take on more and more tasks that are still reserved for electronic devices today. The optimism of researchers farzadfard and lu seems boundless: they believe their development will give a boost to almost all areas of synthetic biology.

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