
He survived a terrifying accident. Now this U of T biologist wants to give our cells an upgrade.
Published on August 24, 2023

Taking a breath … or not
His team is also exploring more elaborate ideas. Since 2021, with support from University of Toronto’s Medicine by Design program, which receives funding from the Canada First Research Excellence Fund, the Garton lab has been looking at how to design cells that can survive for long periods without oxygen. “Humans need 21 per cent oxygen in the air to survive, but other animals have an amazing tolerance for low-oxygen environments,” Garton says. He points to Cuvier’s beaked whale, which holds the world record for the longest-ever dive and can survive more than 3.5 hours on a single breath. “Whales can make these deep dives for hours. That ability doesn’t come from an anatomical advantage — their lungs are actually smaller than ours in terms of body mass. It’s a molecular adaptation.” Other animals, such as the Tibetan antelope and the naked mole rat, have similar capabilities. Because the genomes of those animals have been completely mapped, Garton and his team can take genes they think are responsible for low-oxygen tolerance, synthesize that DNA and then combine it with human tissue, testing it at lower and lower levels of oxygen. They are hoping to solve one of the problems that has plagued attempts to grow new heart tissues from stem cells. About 95 per cent of these tissues die from lack of oxygen when they’re implanted, because it takes about a week for new blood vessels to form. “We’re giving the cells batteries so they can run by themselves until they get hooked up to the grid,” says Garton. In the future, the approach might form the basis of a gene therapy for people at high risk of stroke and heart attack, enabling their brain and heart tissue to survive longer without oxygen.Catching some rays
Another project is even further out. NASA has identified the deadly gamma rays in space — which shred human DNA — as one of the key challenges for future missions to Mars. It’s difficult and expensive to equip a spaceship with radiation shielding, so Garton’s team is trying a different approach. “I thought, rather than try to block rays, just accept them as a factor.” Humans are exposed to low levels of radiation every day — uranium in the soil, radon in various building materials, even radium in our blood and bones — and our cells work to repair any damage this might cause. “We already have that capability,” says Garton. “Now, what we want to do is find a way to juice it up.” Again, the lab looked to the animal world for possible solutions. What they found was the tardigrade, a 0.04-mm-long aquatic animal that can tolerate all manner of extreme conditions, including boiling water, subzero temperatures and being shot out of a gun at 3,000 kilometres an hour. It can also survive space travel. When exposed to high doses of radiation, the tardigrade expels 95 per cent of the water in its body, reducing metabolic activity to almost nil. In this desiccated state, its cells build a protein called Dsup (short for “damage suppressor”), which binds to DNA and is theorized to shield the tardigrade from further harm. No other animal can create Dsup, so Garton’s team has been searching for ways to program human cells to mimic this capability. Early results with an irradiator have shown 20 per cent reduction in DNA damage. They are planning more advanced tests with the NASA-funded Space Radiation Laboratory at the Brookhaven National Lab in Long Island, N.Y. There could be applications for this research closer to home, protecting people whose jobs expose them to radiation. But this work also speaks to a broader story about who we are as a species, where we came from and where we’re going. Space is an extreme example of an environment that’s beyond the design specs of the human body. But even on the ground, we’re moving out of our evolutionary comfort zone. For instance, many of the most groundbreaking ideas in medicine — like growing replacement organs to replace failing ones — could require us to do some molecular tinkering to persuade our bodies to accept them. “The world we now live in is going to require synthetic biology and our own design, in order to allow us to take those next steps,” says Garton. “It’s definitely a different type of exploration than climbing,” says Garton. “But probably even more exciting.” Photography: Colin SneydThe post He survived a terrifying accident. Now this U of T biologist wants to give our cells an upgrade. appeared first on MaRS Discovery District.
