Billions of years before hominids sharpened sticks into stabbing weapons, bacteria invented spears. Specifically, they invented transforming spears—structures that could almost instantly unfold from flat, coiled ribbons into long, pointed cylinders. They use these weapons to wage war on other microbes. And now, scientists—descendants of those early stick-sharpening hominids—are planning to tweak these bacterial javelins, and deploy them as tools for research, medicine, and more.
The story of the spears starts in 1938, with an American biologist named Tracy Sonneborn and his favorite organism—a hairy, single-celled, slipper-shaped organism called Paramecium. Sonneborn discovered that some strains of Paramecium are exceptionally violent, and can kill their more sensitive peers by releasing small particles into their environment.
Those particles turned out to be domesticated bacteria called Caedibacter that live inside the killer strains. When they’re released into the environment, they get gobbled up by other paramecia and shunted into a storage compartment called the vacuole. That’s where they unleash their spears.
These weapons are proteins called ‘Type 51 refractile bodies,’ or R bodies for short. When the bacteria first produce them, they take the form of rolled-up ribbons. But in the acidic conditions on a paramecium’s vacuole, the ribbons extend from the inside, stretching out by almost 40 times and transforming into a long, tapered tube. “Imagine a paper yo-yo,” says Jessica Polka from Harvard Medical School.
The extended R bodies puncture the vacuole, releasing the trapped bacteria. These then poison the paramecia in an as yet unidentified way, perhaps by releasing some kind of toxin. So, the killer paramecia do away with their competitors by seeding the world around them with Trojan bacteria; these get taken in by other paramecia, before going apeshit with their spears and poisons.
Many scientists have pieced together this fascinating bit of natural biology over the last eight decades. But when Polka heard about the R bodies, she realized that she could repurpose them into tools for delivering specific molecules into cells. After all, that’s exactly what Caedibacter naturally use them for. “I thought we could further domesticate this natural protein machine, tune it to behave differently, modify, and manipulate it to make it work for us,” she says.
Working with Pamela Silver, Polka took the genes that Caedibacter uses to make R bodies and transferred them to bacteria that laboratory scientists are most familiar with. She then mutated these genes to identify R bodies that change shape under different conditions. It’s acidity that matters: Lower the pH and they extend; raise it and they retract. But Polka developed a wide range of R bodies that change shape at different pH thresholds.
That’s just the start. She now wants to engineer the R bodies to trigger under different conditions, rather than just acidity—temperature, perhaps, or even light levels. She also wants to study R bodies from other species of bacteria, which have a wide range of properties.
Why? “I think about them as switches,” says Polka. “It’s nice to have a panel that can activate under different conditions. You can imagine using them to release a certain cargo under specific conditions.” By encapsulating the tailored R body with, say, a drug or piece of DNA, she wants to create programmable packages that would sneak molecules of interest into a cell and release them on demand. Better still, she could do this many times over because the R bodies are reversible machines. The long spears can retract into coiled ribbons before extending out again, for at least a hundred cycles if not more.
“There is just so much weird and awesome stuff that biology can do and it’s really interesting to see how it might be applied in different contexts,” says Christina Agapakis, a synthetic biologist from Ginkgo Bioworks.
“Not that many years ago, CRISPR was something weird and esoteric that microbiologists were studying,” she adds, referring to the gene-editing technique that bacteria invented, scientists discovered, and everyone is debating. “R bodies may not be quite as newsworthy but it’s so exciting to think about how many fascinating biological processes are hiding in obscure academic literature or still undiscovered.”
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