Giving astronauts tardigrade toughness will be harder than we hoped

How can we protect space explorers from cosmic radiation without enclosing spacecraft in huge layers of lead? Some have suggested dosing them with the tardigrade DNA-protecting protein – but that won’t be that simple.

Corey Nislow and colleagues at the University of British Columbia in Vancouver have shown that a protein produced by tardigrades called Dsup, short for damage suppressor, can protect against an even wider range of mutation-inducing chemicals than we knew, in addition to radiation. But it also has a tradeoff: it reduces the fitness of cells and can even kill them.

“There’s a cost for every benefit we’ve seen,” Nislow says.

Tardigrades are tiny animals known for their ability to survive stress, especially when exposed to extreme temperatures, dried, subjected to radiation, and even exposed to the vacuum of space. In 2016, Dsup was shown to be one of the keys to their strength. When human cells were genetically engineered to produce Dsup, they became more resistant to radiation with no reported downsides.

This led to the idea that people could be protected from radiation and mutagenic chemicals by giving them Dsup. One way to do this would be to inject them with mRNAs encoding Dsup encased in lipid nanoparticles (LNPs) – the same technology used in mRNA covid vaccines.

“Two or three years ago, I fully agreed with the idea that, deliver Dsup mRNA in an LNP to crew members on space missions and you will not have changed their genome, but you will have provided them with a very effective countermeasure against DNA damage,” Nislow says.

But his team has now conducted in-depth studies on yeast cells engineered to produce Dsup. They found that very high levels were deadly and even lower levels harmed cell growth.

Dsup appears to protect the DNA by physically surrounding it, Nislow explains, but it also makes it more difficult for proteins to access the DNA to make RNA or to replicate the DNA before cell division. It’s also harder for DNA repair proteins to access DNA: the team found that in cells with low levels of repair proteins, Dsup could be fatal, likely because crucial repairs haven’t taken place.

It may be possible to use Dsup to protect people, animals and plants traveling in space, Nislow says, but it will be crucial to ensure that Dsup is produced only in the cells where it is needed and at the appropriate levels.

“I completely agree,” says James Byrne of the University of Iowa, whose team is studying whether Dsup can help protect healthy cells during cancer radiation therapy.

If Dsup were produced continuously in every cell of the human body, it would likely have a significant health cost, Byne says, but if it was only produced temporarily when needed, it could be beneficial.

“It is entirely true that beyond a certain dose, Dsup can have toxic effects,” explains Simon Galas of the University of Montpellier in France. However, his team showed that low levels of the protein can extend the lifespan of nematode worms by protecting them against oxidative stress. There is much left to discover about how Dsup works, he says.

Jessica Tyler of Weill Cornell Medicine in New York state also modified yeast to produce Dsup. At levels lower than Nislow tested, it appears to have beneficial effects without an effect on growth, she says.

“So I disagree that the protection provided by Dsup comes at a significant cost,” says Tyler. But she agrees that ensuring Dsup is produced at the right levels is crucial.

Getting the right cells in the body to produce the right levels of Dsup cannot be achieved with existing technology, but Nislow is confident it will become possible. “There is so much money and attention given to delivery systems,” he says. “This is a problem that so many people in pharma are motivated to solve.”