Searching Tardigrades for Lifesaving Secrets

By Steph Yin
15Feb

“Researchers are drawing inspiration from the proteins that they think let hearty water bears cheat time by decelerating their biology.

There are many instances in medicine when it would be helpful to stop, or greatly slow down, time. Doing so could spare a limb from amputation, prevent paralysis after a stroke or save your life following a heart attack.

Across the tree of life, there are many organisms that can essentially cheat time by decelerating their biology. Chief among them is the tardigrade, a creature no bigger than a speck of sand that can survive severe temperatures and pressures, outer space and all sorts of apocalyptic scenarios by entering a dormant state called anhydrobiosis.

A team at Harvard Medical School is studying tardigrades in hopes of finding medical treatments that halt tissue damage. In particular, the scientists are drawing inspiration from special proteins suspected to help tardigrades achieve suspended animation. They aim to synthesize a version of these proteins that can enter human cells and pause processes leading to cell death.

“When somebody is wounded, there’s a window of time they have to get to a medic or a hospital. So our overarching goal is: how do you prolong that time?” said Pamela Silver, a professor of systems biology.

Also known as a water bear or moss piglet, a tardigrade looks something like a croissant with eight pudgy legs under a microscope. The invertebrates live just about anywhere there’s water, from everyday settings — like a parking lot or handful of moss — to the most extreme environments on Earth, like deep-sea trenches, hot springs, the peaks of the Himalayas and the depths of Antarctic ice.

During anhydrobiosis, tardigrades curl into a desiccated ball called a tun and lower their metabolism to 0.01 percent of normal. They can stay as tuns for decades and resume business as usual almost immediately after being rehydrated.

In 2017, scientists discovered unique proteins, called tardigrade-specific intrinsically disordered proteins, that might help put the creatures’ cells in a protective state during anhydrobiosis.

It’s still unclear exactly how these proteins work, said Roger Larken Chang, who directs Dr. Silver’s lab. Preliminary research suggests that they might form a biological glass that physically immobilizes everything in a cell during periods of stress. Dr. Chang is surveying these intrinsically disordered proteins, as well as proteins associated with stress tolerance in other organisms.

To lay the groundwork for engineering a new synthetic protein, Dr. Silver and Dr. Chang teamed up with Debora Marks, a computational biologist at Harvard whose lab has created an algorithm that can search millions of protein sequences for recurring patterns.

“You can use that, in turn, to understand things about protein structure, function, effects of mutation or, even more so, to generate sequences for design,” Dr. Marks said.

In December, the team was awarded a contract from the Defense Advanced Research Projects Agency, or Darpa, the federal agency that funds the development of technologies of interest to the U.S. military. Darpa, is particularly interested in protein-based therapies to stall bleeding and tissue death in traumatic injuries, Dr. Silver said.

Beyond combat, there are many other potential applications, including refrigeration-free preservation of protein-based drugs, eggs for in vitro fertilization or organs for transplantation, Dr. Chang said. In the very far future, the work could even pave the way for preserving whole, live bodies, which would be useful for space travel or emergency scenarios.

“It seems far-fetched, but if we demonstrate efficacy at the level of cells and tissues, it’s possible to start thinking about these things,” he said.

Plus, she added: “There are many things that sound crazy that organisms, like tardigrades, actually do.”

“That’s the surprising thing,” she said: “There’s a lot out there in nature.”

 

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