BactChat: a new DNA-based messaging service?

You are unlikely to see bacteria using Snapchat, Twitter or Instagram anytime soon, but Marken & Murrey (1) recently explored a new method for intercellular communication – DNA messaging!

What did they do?

In 2012, Ortiz and Endy (2) proposed a new mechanism by which cells could communicate called DNA messaging (Fig. 1a). Using gene transfer, they could transmit DNA-encoded messages between different cell populations or consortia.?

This construct (1) includes a ‘sender’ population of bacteria containing a message (a DNA-encoded sequence to produce YFP) and an array of different single-guide RNA (gRNA) binding sites. The ‘receiver’ populations express one of the matching gRNAs and a Cas9 enzyme designed to degrade a specific site. If the gRNA in the ‘receiver’ cells matches one of the gRNA binding sites from the DNA message, then the Cas9 enzyme destroys the message and information is lost. As such, a message will only be received if the ‘receiver’ cell population does not have a gRNA matching the array on the DNA message from the ‘sender’ (Fig 1.b). #CRISPR #crisprcas9

Marken & Murrey (1) adapted this technology by introducing programmable DNA editors. This allows a property called ‘mutability’ or the ability to change, adapt and respond to the message.

They achieved this by encoding serine integrases into E. coli that add, remove, or swap the different gRNA binding sites. These could be conditionally expressed in the ‘sender’ population cells i.e. when expressed, this swap changes the message and therefore the destination of the message as well.??????? #syntheticbiology

Why is this so cool?

A dream of synthetic biology is not just to change the biology of a single bacteria, but to engineer different populations of interacting cells. This could allow sharing of metabolic burdens and therefore advanced properties in metabolic engineering or #biocomputing (3)!

Typically, consortia communication is achieved through small molecule communication, such as metabolite-based quorum sending. DNA messaging could have three major advantages over small molecule communication. First, many different DNA messages can be sent through one channel. Second, each individual DNA message can contain lots of different pieces of information. And third, the DNA message can change and adapt over time. Together, this makes DNA messaging a unique way to transmit complex information! ????

Where could this be used?

One of the most interesting examples where this could be is in DNA-based memory through #DNA writing and recording. This exciting new field could allow living biosensors or the ability to trace cellular lineages (4). Here, DNA messaging could allow consortium-based responses to the DNA recordings without having to compromise any information! #datastorage

So stay ready and stay hyped. The future could be filled with a storm of bacterial-based social networks such as MicroGram, CellBook or even BioSwipe – “for finding love at a cellular level”… ??

Author: Kazimir Uzwyshyn-Jones .

Banner: Inga Van den Bossche .

(1) Marken, J.P., Murray, R.M. Addressable and adaptable intercellular communication via DNA messaging.?Nat Commun?14, 2358 (2023). https://doi.org/10.1038/s41467-023-37788-z

(2) Ortiz, M.E., Endy, D. Engineered cell-cell communication via DNA messaging.?J Biol Eng?6, 16 (2012). https://doi.org/10.1186/1754-1611-6-16

(3) Duncker, K.E., Holmes, Z.A. & You, L. Engineered microbial consortia: strategies and applications.?Microb Cell Fact?20, 211 (2021). https://doi.org/10.1186/s12934-021-01699-9

(4) Farzadfard F, Lu TK. Emerging applications for DNA writers and molecular recorders. Science. 2018 Aug 31;361(6405):870-875. doi: 10.1126/science.aat9249