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How can you write data to DNA without changing the base sequence?

Zettabytes—that’s 1021 bytes—of data are currently generated every year. All of those cat videos have to be stored somewhere, and DNA is a great storage medium; it has amazing data density and is stable over millennia.

To date, people have encoded information into DNA the same way nature has, by linking the four nucleotide bases comprising DNA—A, T,  C, and G—into a particular genetic sequence. Making these sequences is time-consuming and expensive, though, and the longer your sequence, the higher chance there is that errors will creep in.

But DNA has an added layer of information encoded on top of the nucleotide sequence, known as epigenetics. These are chemical modifications to the nucleotides, specifically altering a C when it comes before a G. In cells, these modifications function kind of like stage directions; they can tell the cell when to use a particular DNA sequence without altering the “text” of the sequence itself. A new paper in Nature describes using epigenetics to store information in DNA without needing to synthesize new DNA sequences every time.

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© Alengo

Protein structure and design software gets the Chemistry Nobel

On Wednesday, the Nobel Committee announced that it had awarded the Nobel Prize in chemistry to researchers who pioneered major breakthroughs in computational chemistry. These include two researchers at Google's DeepMind in acknowledgment of their role in developing AI software that could take a raw protein sequence and use it to predict the three-dimensional structure the protein would adopt in cells. Separately, the University of Washington's David Baker was honored for developing software that could design entirely new proteins with specific structures.

The award makes for a bit of a theme for this year, as yesterday's Physics prize honored AI developments. In that case, the connection to physics seemed a bit tenuous, but here, there should be little question that the developments solved major problems in biochemistry.

Understanding protein structure

DeepMind, represented by Demis Hassabis and John Jumper, had developed AIs that managed to master games as diverse as chess and StarCraft. But it was always working on more significant problems in parallel, and in 2020, it surprised many people by announcing that it had tackled one of the biggest computational challenges in existence: the prediction of protein structures.

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© Johan Jarnestad/The Royal Swedish Academy of Science

Mice made transparent with a dye used in Doritos

Zihao Ou, who helped develop this solution, holds a tube of it.

Enlarge / Zihao Ou, who helped develop this solution, holds a tube of it.

One key challenge in medical imaging is to look past skin and other tissue that are opaque to see internal organs and structures. This is the reason we need things like ultrasonography, magnetic resonance, or X-rays. There are chemical clearing agents that can make tissue transparent, like acrylamide or tetrahydrofuran, but they are almost never used in living organisms because they’re either highly toxic or can dissolve away essential biomolecules.

But now, a team of Stanford University scientists has finally found an agent that can reversibly make skin transparent without damaging it. This agent was tartrazine, a popular yellow-orange food dye called FD&C Yellow 5 that is notably used for coloring Doritos.

Playing with light

We can’t see through the skin because it is a complex tissue comprising aqueous-based components such as cell interiors and other fluids, as well as protein and lipids. The refractive index is a value that indicates how much light slows down (on average, of course) while going through a material compared to going through a vacuum. The refractive index of those aqueous components is low, while the refractive index of the proteins and lipids is high. As a result, light traveling through skin constantly bends as it endlessly crosses the boundary between high and low refractive index materials.

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A single peptide helps starfish get rid of a limb when attacked

A five-armed starfish, with orange and yellow colors, stretched out across a coral.

Enlarge (credit: Hal Beral)

For many creatures, having a limb caught in a predator’s mouth is usually a death sentence. Not starfish, though—they can detach the limb and leave the predator something to chew on while they crawl away. But how can they pull this off?

Starfish and some other animals (including lizards and salamanders) are capable of autonomy (shedding a limb when attacked). The biology behind this phenomenon in starfish was largely unknown until now. An international team of researchers led by Maurice Elphick, professor of Animal Physiology and Neuroscience at Queen Mary University of London, have found that a neurohormone released by starfish is largely responsible for detaching limbs that end up in a predator’s jaws.

So how does this neurohormone (specifically a neuropeptide) let the starfish get away? When a starfish is under stress from a predatory attack, this hormone is secreted, stimulating a muscle at the base of the animal’s arm that allows the arm to break off.

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DNA-based bacterial parasite uses completely new DNA-editing method

Top row: individual steps in the reaction process. Bottom row: cartoon diagram of the top, showing the position of each DNA and RNA strand.

Enlarge / Top row: individual steps in the reaction process. Bottom row: cartoon diagram of the top, showing the position of each DNA and RNA strand. (credit: Hiraizumi, et. al.)

While CRISPR is probably the most prominent gene-editing technology, there are others, some developed before and since. And people have been developing CRISPR variants to perform more specialized functions, like altering specific bases. In all of these cases, researchers are trying to balance a number of competing factors: convenience, flexibility, specificity and precision for the editing, low error rates, and so on.

So, having additional options for editing can be a good thing, enabling new ways of balancing those different needs. On Wednesday, a pair of papers in Nature describe a DNA-based parasite that moves itself around bacterial genomes through a mechanism that hasn't been previously described. It's nowhere near ready for use in humans, but it may have some distinctive features that make it worth further development.

Going mobile

Mobile genetic elements, commonly called transposons, are quite common in many species—they make up nearly half the sequences in the human genome, for example. They are indeed mobile, showing up in new locations throughout the genome, sometimes by cutting themselves out and hopping to new locations, other times by sending a copy out to a new place in the genome. For any of this to work, they need to have an enzyme that cuts DNA and specifically recognizes the right transposon sequence to insert into the cut.

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