Published On: Thu, Mar 14th, 2019

Harvard study unlocks a key to regeneration

It’s also noteworthy, she added, because the three-banded panther worm represents a new model system for studying regeneration.

“Previous work on other species helped us learn many things about regeneration,” she said. “But there are some reasons to work with these new worms.” For one thing, they’re in an important phylogenetic position. “So the way they’re related to other animals … allows us to make statements about evolution.” The other reason, she said, is, “They’re really great lab rats. I collected them in the field in Bermuda a number of years ago during my postdoc, and since we’ve brought them into the lab they’re amenable to a lot more tools than some other systems.”

While those tools can demonstrate the dynamic nature of the genome during regeneration — Gehrke was able to identify as many as 18,000 regions that change — what’s important, Srivastava said, is how much meaning he was able to derive from studying them. She said the results show that EGR acts like a power switch for regeneration — once it is turned on, other processes can take place, but without it, nothing happens.

“We were able to decrease the activity of this gene and we found that if you don’t have EGR, nothing happens,” Srivastava said. “The animals just can’t regenerate. All those downstream genes won’t turn on, so the other switches don’t work, and the whole house goes dark, basically.”

While the study reveals new information about how the process works in worms, it also may help explain why it doesn’t work in humans.

“It turns out that EGR, the master gene, and the other genes that are being turned on and off downstream are present in other species, including humans,” Gehrke said.

“The reason we called this gene in the worms EGR is because when you look at its sequence, it’s similar to a gene that’s already been studied in humans and other animals,” Srivastava said. “If you have human cells in a dish and stress them, whether it’s mechanically or you put toxins on them, they’ll express EGR right away.”

The question is, Srivastava said, “If humans can turn on EGR, and not only turn it on, but do it when our cells are injured, why can’t we regenerate? The answer may be that if EGR is the power switch, we think the wiring is different. What EGR is talking to in human cells may be different than what it is talking to in the three-banded panther worm, and what Andrew has done with this study is come up with a way to get at this wiring. So we want to figure out what those connections are, and then apply that to other animals, including vertebrates that can only do more limited regeneration.”

Going forward, Srivastava and Gehrke said they hope to investigate whether the genetic switches activated during regeneration are the same as those used during development, and to continue working to better understand the dynamic nature of the genome.

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Science & Technology – Harvard Gazette

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Harvard study unlocks a key to regeneration