The Regenerator

If a hydra breaks in two, each half of the ageless sea creature grows into a fully formed organism. Planarian worms, axolotls, sea stars, and certain geckos regrow lost body parts as well, but this select club excludes humans and other mammals. People can regenerate small pieces of tissue, but lost limbs are gone forever.

The idea that a person could grow a new arm or leg sounds like a dispatch from the distant future. Caltech professor of biology Lea Goentoro chases this future in her laboratory. Thanks to seed-grant funding from members of the Division of Biology and Biological Engineering (BBE) Chair’s Council, Goentoro and her students will try to persuade the moon jellyfish, an organism not known to regenerate in the wild, to regrow appendages.

Goentoro (left) consults with graduate student Fayth Tan and research technician assistant Martin Heithe inside her laboratory in Caltech’s Broad Center for the Biological Sciences.

“Small grants make it easier to open up new questions and new directions,” Goentoro says. If the experiment is successful, then Goentoro’s team will try to induce regeneration in other creatures, including some much more closely related to humans.

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“[Caltech is] a place where people help you pursue risky ideas. It’s a place to do something different.”
- Lea Goentoro

What Works for the Jellyfish

It was serendipity that introduced Goentoro to the moon jellyfish. When she came to Caltech in 2011, she met John Dabiri, then a professor of aeronautics and bioengineering and today a visiting associate in aerospace, who sought the secrets of jellyfish propulsion. Dabiri inspired Goentoro to work with the creatures, and she and a student noticed something strange. When a moon jellyfish loses a limb or two, it rotates the remaining appendages to reorganize its body and become symmetrical once again.

Juvenile moon jellies float in a jar in Goentoro’s laboratory.

 

This remarkable flexibility led Goentoro to wonder whether the organism possessed the tools for regeneration even though it had not demonstrated this ability in the wild. She and her team designed an experiment that departed from most research, which, she says, focuses on organisms already known to regrow limbs. “What is not done enough is to look at animals that don’t regenerate and ask the question, ‘How do we get them to regenerate?’”

To answer that question, Goentoro exposes moon jellyfish to a variety of new stimuli to find out whether changes in their environment can spur regeneration. But this investigation aims to do more than spur a jellyfish to grow a new limb. The crux of Goentoro’s research is to identify triggers. Her team will use antibodies that react to particular proteins in order to identify those that are active during regeneration. The researchers also sequence RNA to discern which genes are expressed.

The results could point to the molecular pathways organisms need to regrow limbs, which raises a tantalizing possibility: Those pathways could be common across a wide swath of living things, including mammals. “The question,” Goentoro says, “is whether this is an insight that is only applicable to jellyfish, or whether we can apply it to other organisms.”

Small Grants, Big Ideas

Limb regeneration in mammals sounds so ambitious that major health funders would hesitate to support such research, Goentoro says. That is why seed grants such as the BBE Chair’s Council award have a big impact. “With this funding, we can do the first experiments,” she explains. Even a glimpse of preliminary success could prompt a federal agency to take a chance on more formidable endeavors.

Goentoro cites the “closeness of Caltech” as a foundational element of her work. The seed grant came about because of a chance meeting on campus, an opportunity to share ideas with a member of the BBE Chair’s Council who regularly visits faculty across campus to learn about their research. In addition, Goentoro and her team work with Caltech’s Center for Environmental Microbial Interactions (CEMI). Inspired by the ways in which corals come back from injury, she plans to collaborate with CEMI scientists to determine whether the microbiome, which influences so many biological processes, affects an organism’s ability to regenerate.

A human is a far cry from a coral or jellyfish, but the question of whether it may be possible for us to regenerate body parts carries enormous implications. If science can help humans regrow lost digits or limbs, then the first steps toward achieving that goal may be happening right now at Caltech.

“It’s a place where people help you pursue risky ideas,” Goentoro says. “It’s a place to do something different.”

To learn more about how you can provide crucial seed funding for projects like Goentoro’s, contact Bettie Woods, executive director of development, individual giving, at (626) 395-6311 or bwoods@caltech.edu.

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