American Scientist

A newly discovered protein from Earth’s toughest animal is inspiring breakthrough therapies for cancer and cardiovascular disease.

Tardigrades, often called water bears or moss piglets, are microscopic creatures that can survive just about anything: boiling heat, freezing cold, and crushing pressure. In fact, tardigrades are the only known animal to survive in outer space. They can also endure radiation levels up to 2,000 times higher than what human cells can tolerate. Naturally, scientists have long wondered: How do they do it?

In 2016, researchers uncovered one of the tardigrades’ secrets: a gene with a sequence unlike any other known to exist in nature that makes a protein found only in tardigrades. When the researchers introduced this protein into human cells, those cells also became more resistant to radiation. The protein was named damage suppressor, or Dsup, because it helps protect DNA from harm.

Since then, researchers around the world have been working to discover exactly how Dsup works. As a biochemist studying Dsup, my goal is to uncover how this protein functions and one day use these insights to design new therapies that protect human cells from DNA damage.

Tardigrades’ DNA Defender

Scientists have proposed several explanations for Dsup’s remarkable ability to protect DNA from radiation, but no single explanation has gained broad consensus in the field.

In my recent work, I found that Dsup interacts strongly with DNA. It clings tightly to DNA not just at one spot but along its entirety. Dsup doesn’t have a fixed form. Instead, it behaves like a spaghetti noodle in water, constantly shifting, bending, and adopting many different shapes. When it binds to DNA, it causes the strands to slightly unwind, like a zipper being loosened. This gentle unwinding may make DNA less susceptible to damage when exposed to radiation.

Another theory is that Dsup acts like a shield, coating and physically blocking radiation from striking DNA. Yet another explanation is that it boosts the cell’s repair machinery, fixing damage before it causes detrimental effects.

In fact, it’s possible many of these models could be true at the same time. Since Dsup protects against many types of radiation—as well as the toxic by-products created from radiation damage—it’s likely this mysterious protein has multiple functions.

Using Dsup to Advance Science

Scientists are exploring whether Dsup could be used in medicine, especially in diseases where DNA damage plays a major role. Because nearly all cancers involve DNA damage, some researchers think Dsup, or treatments inspired by it, could help prevent cells from becoming cancerous. It might also protect healthy tissue during cancer treatments such as radiation or chemotherapy, which work by damaging DNA in cancerous cells but often harm healthy cells in the process.

Dsup’s potential in human health extends much further. For instance, during heart attacks and strokes, organ tissues experience bursts of oxidative stress—chemical reactions that lead to extensive DNA damage. Oxidative stress can worsen disease severity and long-term outcomes for patients who develop cardiovascular diseases. If Dsup could protect DNA during these events, it might be able to reduce the cellular damage.

When scientists introduced Dsup into human cells, those cells became more resistant to radiation.

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Early animal studies are showing promising results, demonstrating that mammals can produce Dsup and elicit similar effects. In one study, scientists used an injection of messenger RNA (mRNA)—similar to the technology behind COVID-19 mRNA vaccines—to deliver the genetic instructions to produce Dsup in mice. (See, “Messenger RNA Can Do More for Medicine") When the mice were later exposed to high doses of radiation, those producing Dsup had far less DNA damage than untreated mice, suggesting real protective power in living organisms.

Dsup’s powerful potential extends beyond medicine. When agricultural researchers engineered rice and tobacco plants to produce Dsup, the plants became more resistant to radiation—an exciting indication of Dsup’s potential to mitigate crop damage. In space biology, Dsup could help astronauts withstand the intense cosmic radiation that limits long-term missions.

And in a futuristic twist, some scientists are investigating how creatures such as tardigrades could be used for ultrastable data storage. Current digital media is susceptible to damage from environmental conditions such as high temperatures and high levels of radiation. If stored data were converted into a DNA sequence and genetically engineered into the tardigrade genome, Dsup could aid in protecting it from extreme conditions.

Since Dsup’s discovery nearly a decade ago, the scientific community has been excited about the potential technological advancements that Dsup could enable. But significant research is still required to fully understand how this mysterious protein functions in living organisms. Despite the work ahead, the story of Dsup demonstrates how scientists can learn from tiny animals such as tardigrades.

This article was adapted from a piece that was previously published on The Conversation (theconversation.com).