The most resilient animal known to science – the tardigrade – is yielding its secrets, with the first work at the atomic level investigating the way the animal survives extreme stress.
Tardigrades are microscopic, eight-legged animals sometimes referred to as water bears. They live in moss all over the world, which also inspired the whimsical and frankly mammalocentric name moss piglet.
No mammal could survive what a tardigrade can tolerate. Under environmental stress such as dehydration or extremes of temperature they shrink into a “tun” state in which their metabolism all but stops. In this state they can survive without water for decades, tolerate high doses of gamma and X-ray radiation and survive temperatures from -272°C to 150°C. They have also breezed through 10 days in the vacuum of space.
In most other organisms, these sorts of stresses destroy the DNA in cells, but tardigrades have a damage-suppressor protein (Dsup) that somehow shields the DNA. Now, Marina Mínguez-Toral and colleagues at the Centre for Plant Biotechnology and Genomics in Madrid, Spain, have performed a simulation of the interaction between Dsup and DNA that suggests an explanation.
The team modelled a system of two Dsup molecules and DNA, comprising more than 750,000 atoms, which required “days and days” on a supercomputer. “The equations of motion must be solved for each of these atoms 50 million times to get a simulation lasting 100 nanoseconds,” says Mínguez-Toral.
The researchers’ modelling of all the atoms in the protein and all their electrostatic interactions shows that the protein is “intrinsically disordered” and highly flexible, and seems to be able to adjust its structure to precisely fit DNA’s shape.
“Our study reveals that the electrical effects underlying the positive-negative charge attractions determine the dynamics of the structural changes of Dsup in its interaction with DNA,” says Mínguez-Toral. “We believe this electric shielding is paramount in protecting DNA from radiation.”
Figuring out precisely how tardigrades tolerate such extremes could be useful in several ways. “Right now the main applications we are actively working on are the stabilisation of pharmaceuticals and the engineering of stress tolerant crop plants,” says Thomas Boothby, who works with tardigrades at the University of Wyoming.
Other possibilities include cancer treatment, as well as futuristic applications such as human hibernation and space travel – people going to Mars might be modified to be more resistant to radiation, for example. In the lab, human kidney cells have been genetically modified to express Dsup from tardigrades, and these cells showed a reduction of 40 to 50 per cent in the DNA damage caused by X-rays.
The next stage would be to modify all the cells in another organism, and lab favourites such as the roundworm and the fruit fly look like good candidates, says Boothby. However, Mínguez-Toral and colleague Luis Pacios make the point that we don’t know why Dsup evolved, and we need to figure that out before we start thinking about modifying whole organisms.
Journal reference: Scientific Reports , DOI: 10.1038/s41598-020-70431-1
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