How to protect astronauts from galactic radiation without covering the spacecraft with multi-ton lead plates? One idea is to provide them with natural tardigrade protection. However, it turns out, it's not that simple.
Tardigrades are tiny animals famous for their ability to survive extreme conditions: extreme temperature changes, complete dehydration, lethal doses of radiation, and even the vacuum of space. In 2016, it was shown that one of the keys to their endurance is the protein Dsup (damage inhibitor). When human cells were engineered to produce Dsup, they became more resistant to radiation with no apparent negative effects.
A reasonable idea arose to protect humans from radiation and mutagens with the help of Dsup. One way is to introduce mRNA encoding Dsup into lipid nanoparticles, similar to mRNA vaccine technology against Covid-19.
“Twenty or thirty years ago, I was all for this idea: let's give Dsup mRNA in lipid nanoparticles to crew members. We wouldn't edit their genomes, but we would give them strong protection against DNA damage,” said Professor Corey Nislow from the University of British Columbia.
The lab he heads has conducted extensive research on yeast cells engineered to produce Dsup, the results of which have been posted as a preprint on bioRxiv. It turns out that very high levels of the protein can be deadly, and even moderate levels slow cell growth.
The biologist explained that Dsup appears to protect DNA by physically enclosing it. But this makes it harder for other proteins to reach the DNA – such as RNA synthesis or replication before cell division. The work of DNA repair proteins is also complex. As a result, in cells with low levels of such proteins, Dsup can be lethal, perhaps because important repair processes do not occur.
“Every benefit we see comes with a cost,” Nislow concluded.
According to him, using Dsup to protect humans, animals and plants in space is still possible – but to do this it is necessary to ensure that the protein is produced only in the necessary cells and in the right quantities.
“I absolutely agree,” says James Byrne of the University of Iowa, who is studying whether Dsup can help protect healthy cells during cancer radiation therapy.
Radiation oncologists say if Dsup is continuously produced in all cells of the human body, it will likely have serious health effects. But if its production is turned on only temporarily, then when needed, the effect can be positive.
Professor Simon Gala from the University of Montpellier affirmed: “It is certainly true that above a certain concentration, Dsup can have toxic effects.”
However, his team has shown that low levels of this protein can prolong the lifespan of nematodes by protecting them from oxidative stress. There's still a lot to learn about exactly how Dsup works, he adds.
Jessica Tyler of Weill Cornell Medicine has also engineered yeast to produce Dsup. At lower concentrations than what Nislow's team studied, the protein appeared to have beneficial effects without affecting cell growth, she said.
“Therefore, I do not agree that the protection that Dsup provides comes at a high cost,” the researcher emphasized.
However, she agrees that controlling the level of protective protein production is indeed extremely important.
It is impossible to teach the body's necessary cells to produce Dsup in optimal quantities using currently available technologies, but Nislow is confident that this will become a reality.
“A lot of money and attention is being poured into distribution systems now. Many experts in the pharmaceutical industry are motivated to solve this problem,” he concluded.
