Studying regenerating salamanders at UMass Boston could pave way for application in human medicine
Assistant Professor of Biology Catherine McCusker calls her Number 76. But 76 is more than just a number. She and other Mexican axolotls at UMass Boston like her demonstrate how animals can regenerate limbs.
“It seems like all species are capable of regenerating as embryos. Embryos are really, really good at that. But for whatever reason, only some species are capable of maintaining that ability to regenerate when they are adults,” McCusker explains. “We’re using the Mexican axolotl to understand how regeneration happens normally in adult animals and what kind of lessons can we pull away from that to apply to human medicine, to regenerative medicine.”
The National Institute of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) has just awarded McCusker $444,004 over the course of three years for her project, The Function of Chromatin Remodeling in the Patterning of the Salamander Limb Regenerate. Because the award is an R15 (AREA) grant, the award includes funding for two undergraduate students, as well as three graduate students and a post-doc in McCusker’s Lab. Funding starts on Saturday, September 1.
Beginning her fourth year at UMass Boston, McCusker has been studying regeneration since she was a postdoctoral American Cancer Society fellow. She became fascinated by animals that if amputated at the hand, replace just at the hand, and if amputated at the upper arm, replace all the structures in the arm.
“How does it know? How does it know exactly where it is and how does it know to replace exactly what’s missing? At the heart of it, that’s what we’re trying to answer with this particular grant. Limb regeneration requires ‘old’ cells to become flexible, or plastic, so that they can get new information to replace exactly what is missing –but we really don’t know a lot about how that happens. We are looking at the changes that occur to the structure of the chromatin, where important regeneration genes are located, in these ‘old’ cells that help them acquire new information,” McCusker said.
She and others have discovered that during injury the chromatin, which consists of tightly packed DNA, opens up, allowing for certain regeneration genes to be activated. In her lab, McCusker is able to trick the Mexican axolotls into thinking that a limb has been amputated by removing a square of skin, deviating a nerve, and taking tissue from the opposite side of the limb and putting it there. This means you have what McCusker calls the three basic requirements to regenerate: a wound, a nerve, and positional disparity.
McCusker likens the process to building a house.
“You can have a pile of materials, but the materials don’t make any sense unless you assemble them with a blueprint. It’s the same thing with making a new limb on the Mexican axolotl,” McCusker said. “One of the big picture questions that we’re trying to answer with the grant is what kind of changes are happening to the chromatin structure that make those cells that are contributing to the regenerate capable of making a new blueprint. Because if you think about it, those cells already have blueprint information in them, because they got that when they were an embryo. And so somehow they have to remove some of that “old” information and establish “new” information to replace exactly what’s missing.”
Number 76 is retired now, but others like her could be the key to figuring out a way to eventually apply this work to human medicine.
“These guys are reprogramming naturally. So if we can understand how this is happening, we’ll really be able to understand what’s happening in a tissue culture plate with cells from a patient intended for regenerative therapy, so I think that’s one of the exciting things that we can take out of it,” McCusker said.