Sea Slugs Offer Insights Into Regenerative Medicine

When a person scrapes their knee or breaks a bone, their body works quickly to rebuild cells and tissues to repair the injury. But some species possess highly complex regenerative abilities—regrowing lost limbs or even repairing a damaged heart.

Scientists such as Dr. Luiza de Oliveira Saad, a 2023 Pew Latin American fellow, believe these organisms might offer key insights into how humans heal. Her work in Dr. Peter Reddien’s lab at the Whitehead Institute for Biomedical Research examines a species of mollusk known as a nudibranch, a colorful sea slug with powerful regenerative traits that could someday help advance regenerative medicine.

This interview with Saad has been edited for clarity and length.

Your work in the Reddien lab explores the regeneration process. What’s the goal of this research?

We’re trying to understand why some animals have a strong capacity for regeneration while others don’t. The human ability to regenerate, for example, is quite limited. I believe there are lessons we can learn from other animals.

What species are you studying?

I landed on the Berghia stephanieae, a type of mollusk known as a nudibranch or sea slug, with pretty remarkable regenerative abilities. That means if they’re injured, they can remake complex organs such as the heart or a kidney. While they can’t re-form a head if theirs gets removed, headless nudibranchs are still able to adapt and continue to survive even after losing such a critical body part.

What do you hope to discover?

Courtesy of Luiza de Oliveira Saad

One of the dilemmas in this field is understanding the order of regeneration. An injured animal needs to be able to first identify what organs or tissues they’re missing and where those tissues belong before their bodies can rebuild them. For example, if you remove a limb in a certain species, does the segment of the arm closest to the body re-form and then regenerate into the fingertips? Or do the cells assemble to lay the groundwork for the fingertips first, with the rest of the arm building from that? Different animals regenerate in different ways. I’m trying to understand how the nudibranch does it.

What techniques help you study this?

We use single-cell transcription analysis, which reveals the gene expression profile of individual cells. As part of this work, we segment the animal into the head, heart, trunk, and tail, and we look at regeneration at different points in time—at zero, three, and eight days. Once we collect this single-cell data, we use an imaging technique for mapping genetic material to see which segment of a particular gene is expressed.

What have you found?

Using this single-cell sequencing data, I’ve been able to identify many different clusters of cells, each with its own gene expression signature. These clusters correspond to different tissues, like muscle, kidney, intestine, and more. Having this kind of cellular map is a really important foundation because it tells us which cell types exist in the mollusk and what their molecular identities look like.

With this information in hand, I’m studying how each organ is reestablished during regeneration. Specifically, when the genes associated with those organs turn back on. I can also look at how dividing cells behave: whether they’re dividing within their original tissue, or whether they move to a specific site to support the regenerative process.

Do you see this work being applicable to humans in the future?

I really hope it can be translated to help human lives. Right now, I’m super curious about hearts. Human hearts don’t regenerate, but the mollusks I study can rebuild their hearts from scratch, which is not found in any other animal so far. I think it would be very cool if we could understand the dynamics in those genes that are regenerating the heart and compare that with human genetics. Maybe we can find strategies that would help us manipulate or target human heart regeneration.

What are your long-term goals for this research?

I think Berghias are a good model to study, and I’m trying to use this data to establish my own lab and continue this research in Brazil. I’m curious to see if other species of mollusks, including those we have in Brazil, might regenerate differently from the ones we use in the lab now.

How else do you hope this work will contribute to Latin American science?

I think this research is not very well explored yet in Latin America for various reasons. The resources there are different, and so the opportunity to come to the U.S. and establish a community of collaborators has been amazing. Going back to Latin America with this new knowledge and connections will be a huge contribution because I know I can continue to provide that opportunity to other students in Brazil.

Brazil has amazing scientists, but it’s good to have the chance to meet new people and collaborate worldwide. I believe the progress of research can be better through collaborative partnerships. When you have diverse minds thinking about a problem, I think a solution can be found sooner.