by Brent Foster, Whitney Laboratory, University of Florida
Finding a scientific niche may be a bit like trying to spot a camouflaged dwarf cuttlefish in a saltwater tank. At first, all you can see are rocks and bobbing tendrils of orange finger corals. But if you wait patiently, you might suddenly see the rock morph into something alive and fluttering.
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“You never really know where your life is gonna go,” said Tessa Montague, a post-doc who studies cuttlefish camouflage behavior in the Axel lab at Columbia University. Tessa’s path of self-discovery did not start with a personal aquarium or with a burning curiosity. In fact, she didn’t grow up wanting to be a scientist at all. Not at first, anyway. As a kid, she had dreams of becoming a CIA agent and even kick-boxed her way to a blackbelt.
“This wasn’t a particularly well-thought-out plan,” she said with a chuckle. “But I knew I wanted to go to a good university and probably study science.” She described her time during a summer research program as just an opportunity for another line in her CV. But one day everything changed when she cracked open the top of a chicken egg and zoomed in with a microscope to see an embryo with a tiny little heart beating.
“That just blew my mind,” Tessa said. “And I realized, I think I want to be a scientist.”
She dabbled in a number of animals and projects, from a Master’s thesis in Drosophila embryonic development to PhD rotations with zebrafish development, mouse neuroscience, even yeast transcriptional dynamics. She loved the nuance and idiosyncrasy of each new organism as she developed quirky skills that only scientists can truly appreciate—she proudly told me “I was really good at dissecting fly guts,” a brag you don’t hear too often.
Mice, however, proved too much. Her first experience trying to inject a mouse ended in a bleeding finger, a flying mouse, a ducking post-doc, and shouting all around. All in all, not a natural fit.
But what would be a natural fit after her graduate degree?
“During my PhD, I was thinking about the future and what I wanted to study in my post-doc,” Tessa said. By this point she realized how competitive and terrifying the world of academia could be. But what got Tessa excited and inspired were talks where scientists asked big new questions in new model organisms. “Somehow if I imagined creating my own niche by studying a weird question in a weird system, I felt comfort and excitement rather than fear,” she said.
Then, at the MBL embryology course in Woods Hole, Tessa was introduced to cephalopods and their crazy biology—massive brains, blue blood, three hearts. Oh, and a way of representing the visual world on their skin. She was particularly drawn towards the dwarf cuttlefish.
“It was literally like my whole life flashed before me,” Tessa said. “It’s not that often you get that moment, but everything clicked.” She shared her epiphany with her PhD advisor, who tempered her excitement by reminding her that she should really start with a question and not with an organism. The problem—or perhaps advantage—was that there were so many unanswered questions. Finally, Tessa came up with the idea to use the dwarf cuttlefish’s neurally-controlled camouflage ability to understand how the brain internally processes and perceives the visual world. She just had to choose a lab with the creativity and expertise to help her answer her research question. So she weighed her options.
Option 1: Find a cephalopod lab. They’d have experience raising the animals and designing cephalopod behavioral experiments. But they might not necessarily have expertise in systems neuroscience.
Option 2: Find a systems or molecular neuroscience lab and bring the cephalopods to them. Sure, she’d have to figure out how to keep the animals alive, but the lab would have the resources to develop transgenic animals and the expertise to interpret neural imaging data.
In the end, Tessa chose to take her project to Richard Axel’s lab at Columbia University, which studies olfaction in mice and Drosophila. On the surface, mouse and fruit fly olfaction don’t have much in common with cuttlefish camouflage. But Tessa and her colleagues in the lab share the same fundamental research question: How do animals create an internal representation of the sensory world?
Getting the project started has been bumpy. It took months to get the saltwater system to a point where it could support marine life. And when the cuttlefish finally arrived, they were sickly little animals that wouldn’t eat, let alone camouflage.
“I remember thinking, ‘Oh my god, what if this project completely collapses?’” Tessa recalled. “We’re just putting the animals in the tank and frantically saying, ‘Please do something magical for us!’”
Keeping cuttlefish alive is a chore. They eat and poop a lot, and they’re extremely sensitive to changes in water quality. To feed baby cuttlefish, a lab tech has to count out every single tiny shrimp to make sure the babies are not over- or underfed. And not just for one animal—currently, the facility at Columbia University holds over 200 cuttlefish.
The research can be just as rocky. Tessa’s end goal is to manipulate the dwarf cuttlefish genome and record neural activity during camouflaging. Never mind that no one had sequenced the cuttlefish genome and that virtually zero transgenic tools have been adapted for cephalopods. All of that takes time, setbacks, and a firm determination to see things through.
Once armed with a sequenced genome, an assembled transcriptome, and ATAC-seq data to identify candidate cuttlefish promoters, Tessa is poised to use the meganuclease, I-SceI, to integrate GCaMP and other fluorescent proteins to make the first transgenic cuttlefish.
“Every time I say what method I’m using to make transgenics, someone says, ‘Have you thought about this?’ and then I have this moment when I think, ‘Well, maybe I should try that,’” Tessa said. Choosing the right method to develop tools for a non-model organism requires a certain type of balancing act. At what point do you decide to move on versus give something another chance?
“We don’t have a transgenic cuttlefish yet,” Tessa is quick to say. And with a progeny rate of between 10–50 embryos per spawn, cuttlefish aren’t all that prolific. They also seem pretty sensitive to injections, with a final survival rate approaching 25%.
“It is brutal,” said Tessa. “These embryos test my optimism and hope. They’re just fighting me. But I’m fighting back.”
Studying cuttlefish camouflage has its bright spots, too. At the 2023 SICB conference in Austin, Tessa presented the “highlights reel” of some of her cuttlefish behavioral experiments. Using a digital display that does not emit light, she showed that cuttlefish can camouflage to artificial stimuli. In another experiment mimicking conditions for imaging a cuttlefish brain with a microscope, Tessa demonstrated that a cuttlefish with its head in a harness can camouflage when walking along a fabric treadmill that changes color.
“This has been very encouraging,” she said. That kind of optimism and determination can temper the challenges of scientific research, especially with an animal as bizarre as the dwarf cuttlefish.
Tessa is no slouch when it comes to sharing her research. She created Cuttlebase, a website for public outreach that also shares some of the scientific tools she’s helped develop. Her own personal website hosts a CuttleCam livestream where anyone can play “Where’s Waldo?” and practice identifying interesting cuttlefish behavior, inspiring oohs and awes from viewers all around the world.
Tessa is also quick to admit how humbling it is to work with these amazing animals. In a recent tweet that may well stand as a symbol for biology researchers everywhere, she shared a short video of a dwarf cuttlefish rippling with bands of light and dark.
“I’m learning to speak cuttlefish,” she tweeted, “but I still don’t know what these skin waves mean . . . Any ideas?”
connect with Tessa via Twitter
Connect with ICB blogger Brent Foster