DNA data storage with epigenetics bonus

Plus: Imaging multiplexing, protein degradation, and more.

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Today, we are diving deep into the world of DNA data storage! And have a good Halloween 😎

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DNA data storage with epigenetics bonus

DNA data storage is a promising strategy to improve on current data storage solutions. Image credits Bluefin.

Data storage needs are exploding. Everything needs data: from TikTok videos to AI drug research, even this newsletter! (Not a lot of them, I promise). This is creating a huge problem, since we are starting to run out of space to build data centers, and everyone is after better storage materials.

In nature, DNA is the material for information storage. And DNA data storage is a very active area of research: multiple studies have shown how you can encode and decode information from DNA, like it was an USB stick. Unfortunately, these systems face one big challenge: they are based on the serial (one by one) synthesis of DNA strands, which makes it slow and very costly. Alternatives exist, like for example using DNA hairpins or DNA origami, but they also have limitations, like low throughput of information or stability.

But in today’s paper, the authors took a fresh approach, inspired by epigenetic modifications. In our cells, epigenetic modifications allow to control gene expression without altering the DNA sequence. Instead of expensive DNA synthesis, the team used DNA methylation (adding methyl groups to specific DNA sites) to store data. They call this epi-bit encoding, where methylated sites represent “1” and unmethylated sites represent “0”.

It’s not the simplest method if you are not familiar with data storage (I’m not), so let’s break down the key components:

  1. Epigenetic data encoding via methylation

    DNA methylation involves adding a methyl group to the cytosine bases in the DNA, specifically at CpG sites (sites where a cytosine is followed by a guanine). Using the enzyme DNMT1, the authors controlled the methylation at specific sites, creating a binary system where:

    •  Methylated sites represent “1”, so the epi-bit is on

    • Unmethylated sites represent “0”, so the epi-bit is off

    This binary encoding means that data can be written directly onto DNA molecules by selectively adding or removing methyl groups from specific sites, creating a highly dense and stable storage medium!

  2. Modular DNA design with “movable types” and “templates”

    Borrowing a concept from printing, the team used movable DNA types as customizable strands that can be modified, and templates as guides to position these types for methylation. This allows encoding across multiple DNA molecules in parallel, which speeds up the process and increases the data capacity.

  3. Nanopore sequencing for retrieving data:

    To read the methylation patterns, they used nanopore sequencing, which detects methylation directly based on unique electrical signals from methylated vs. unmethylated bases. This allows the encoded binary data to be retrieved accurately.

  4. Automated platform for large-scale parallelization:

    Finally, the researchers created an automated platform to handle encoding across multiple DNA strands simultaneously. This setup minimizes errors and allows them to store up to 275,000 bits (34 kilobytes) per experiment.

So, how did they test all of this? Well, simple: they encoded some images into the DNA and see what they got back! And the results were very good: they found that the epi-bit encoding was both stable and retrievable, showing minimal degradation or error over time. But another cool part is when they took 60 volunteers and allowed them to use the protocols to store their own text: the data was then sequenced and analyzed by the researchers. They got great results back, with an error rate of only 1.5%, showing how simple this method is!

So, this paper has a few interesting aspects and potential applications:

  •  Cost-Effective and Scalable: Without the need for DNA synthesis, this method reduces costs significantly and is scalable thanks to its parallel encoding capability.

  • Privacy and Accessibility: Since it doesn’t depend on centralized facilities or specialized synthesis, data can be stored locally on DNA, enabling private and secure data storage directly under user control rather than in digital clouds.

This method is a creative, cost-effective leap forward for DNA storage, and it’s packed with potential for secure, long-term data archiving. So, that was a very deep paper, and it’s definitely worth a read!

In other news:

  • Multiplexing with NanoPlex: Multiplexing in fluorescence microscopy is a big challenge. But this study offers a solution. NanoPlex is a new fluorescence microscopy technique that enables highly multiplexed imaging using standard lab equipment. NanoPlex integrates engineered secondary nanobodies with three signal-removal methods OptoPlex (light-based), EnzyPlex (enzyme-based), and ChemiPlex (chemical-based), and it can image up to 21 targets in 3D confocal and 5–8 targets in super-resolution microscopy

  • Protein degradation against Alzheimer’s: Developing new therapeutic strategies for neurodegenerative diseases is extremely important, since they are on the rise pretty much everywhere. This study introduces RING-Bait is a new strategy to selectively degrade protein aggregates, leaving functional proteins unaffected. The team tested it on tau aggregates associated with Alzheimer’s, and RING-Bait successfully reduced tau pathology and improved motor function in mouse models.

  • Making peptides more metal: This interesting study introduces a new strategy to improve folding and mechanical rigidity in metallopeptide nanostructures. By combining heterochiral peptide-derived linkers, the peptides fold into 3D structures that create biomimetic binding pockets and exhibit strong chiral amplification. This unique folding results in a ten times increase in stiffness compared to natural protein materials. The structured peptides also show improved binding and antimicrobial activity compared to their unfolded forms.

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