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At Harvard, Nick Bellono Creates an MBL-Style Lab for Curiosity-Driven Research

“The ǧ����Ƶ is definitely the reason I’m a scientist,” claims Nicholas Bellono, an energetic associate professor of molecular and cellular biology at Harvard University.

Inspired by his vision of “an MBL-style group in which people could explore whatever they are curious about and do it without the constraint of a particular animal model or technique,” Bellono established his biodiverse Harvard lab in 2018, he recently told

Over the past five years, more than 100 animal species have cycled through Bellono’s lab as he “auditions” them as systems for discovering the molecules that drive animal adaptations and behaviors. Many of the animals he has chosen to study – octopus, squid, sea robins, little skates, sharks, sea anemones – stretch back to his experiences at MBL.

“I believe comparative biology is incredibly powerful,” Bellono told Current Biology. “And, simply put, looking somewhere new can teach us something new.”

“Too Good To be True”: Falling in Love with Science at the ǧ����Ƶ

“Like many, my first summer in Woods Hole made a huge impression on me,” Bellono told Current Biology. “It’s a special place in which everyone is highly curious and excited about their work, does creative and fun experiments all day and night, and then hangs out at the beach.”

Bellono hadn’t yet considered a career as a scientist, but his MBL summer dramatically changed that. “I thought: I could get paid to get a Ph.D. and hang out on the beach between playing around with cool animals? This seemed too good to be true.”

Then an undergraduate at Michigan State, Bellono came to Woods Hole through , who invited him to spend a summer working in her MBL Whitman Center lab. To this day, Bellono is grateful to Eisthen for the opportunity, which ended up lighting and inspiring his career path.

Bellono went on to graduate school at Brown University, where he studied cell physiology and neuroscience. His interests led him back to the ǧ����Ƶ in 2014, specifically to the summer lab of of Yale University, a prominent scientist in the field of electrophysiology (measuring the electrical activity of living cells).

“I was trying to establish a preparation for measuring the electrical activity of pigment-producing organelles inside skin cells,” Bellono says. “This experiment involved placing a pipette inside of another pipette to gain access to the organelle (think of Alien with the mouth inside the mouth). A rare example of this experiment had come from the ǧ����Ƶ in squid axons by Liz Jonas.”

Bellono visited Jonas at MBL for instruction and “It sort of worked … Well, I couldn’t quite do what Liz pulled off. But as you’ll appreciate as a theme from my MBL stories, Liz was incredibly generous with her time, advice, and enthusiasm for science. I learned a lot from the visit.”

And Bellono kept going. “True to the ǧ����Ƶ spirit of trying a bunch of stuff until something works, after visiting Liz, I went to the lab of (former MBL Grass Fellow, now at UPenn) to learn to patch clamp isolated endosomes (a type of organelle),” Bellono says. This visit would ultimately lead to their that are critical for eye, hair, and skin pigmentation.

Gaining Technical Prowess

After graduating from Brown in 2015, Bellono pursued postdoctoral training in sensory biology in the lab of at University of California, San Francisco (UCSF). There, he began studying electroreceptors, the specialized cells some fish use to detect very small electrical fields for predation, communication, and navigation. And once again, the road of scientific curiosity led back him to the ǧ����Ƶ.

“I was similarly looking to develop a preparation to measure electrical activity from electroreceptors,” Bellono says. “I had tried several model organisms – glass catfish from the pet store, weakly electric fish, and others” when (University of Maryland), now co-director of the ǧ����Ƶ Neurobiology course, suggested skates.

Bellono worked with Scott Bennett and the late Dave Remsen of the ǧ����Ƶ Marine Resources Center to ship skates to UCSF.

“We didn’t have tanks or anything to keep the animals, so basically I just stayed awake for days doing coffee and beer-powered experiments as long as the cells were healthy,” Bellono says. “Ricardo provided instrumental advice about anatomy and other unfamiliar aspects over the phone while I tried the first cellular dissociations. We later worked with Scott Bennett again, who shipped us catsharks for a comparative study on how skates and sharks differentially tune their receptor cells to detect distinct cues.”

Bellono, (former MBL Grass Fellow, now at UCLA), and Julius published their findings in and in Nature.

It was in Julius’ lab that Bellono “acquired the skills necessary to take an interesting phenotypic problem and reduce it to one molecule: a single protein,” reports an article on Bellono in . “Bellono has applied this method to understand a variety of intriguing animal behaviors and adaptations.”

The Octopus Teachers

When Bellono interviewed for his current position at Harvard, he had become very excited about octopus – especially their arms. “It seems like the arms were doing a lot: sensing and exploring, squeezing into tight places, changing color ...” He wondered if “an open-minded exploration of signal transduction in the octopus arm would be unique and informative for connecting the evolution of proteins to cellular and organismal function,” he told Harvard Magazine.  Although he hadn’t even started working with octopus yet, his enthusiastic “chalk talk” for his interview outlined this very question. To his surprise, he got the job.

Bellono started from scratch at Harvard, building a makeshift facility to hold octopuses in a former classroom. “After we flooded our wing of the Biological Laboratories Building a couple of times, had octopuses escape (and rescued), and lab members started bringing additional new animal models, we realized we needed a proper animal facility,” he says.

“We turned to the ǧ����Ƶ and the New England Aquarium for advice about setting up a seawater facility in Cambridge (not exactly typical) and learned that the ǧ����Ƶ had recently established a cephalopod facility! That was super exciting because ǧ����Ƶ had worked out a tremendous amount in acquiring and housing various cephalopod species and developing experimental tools,” he says. “And they were incredibly generous in providing assistance toward building a community. Special thanks to Bret Grasse, Taylor Sakmar, and Josh Rosenthal, who were incredibly responsive, scientifically engaged, and community oriented.”

In 2020, Bellono’s lab that octopus arms have a specialized “taste by touch” sensory system to explore the seafloor, which the use to respond to prey-derived chemicals and movement. And last year, they published studies showing that both octopus and squid use this system of chemotactile receptors to sense their respective marine environments, but structural adaptations allow them to sense specific molecules suited to distinct physiological roles.

Back at the ǧ����Ƶ, Joshua Rosenthal’s lab reported in 2017 that octopus can edit their own RNA, allowing them to diversify the types of proteins they can make. Bellono wonders whether this RNA editing capacity may produce slight structural shifts in their chemotactile receptors, enabling them to sense what they want as they traverse the seafloor.

The Serendipity of Discovery

Since establishing his Harvard lab, Bellono and his lab members regularly visit the ǧ����Ƶ to obtain specimens or for longer-duration experiments. “And, perhaps most true to the ǧ����Ƶ spirit, we regularly stumble upon other species and questions during our visit,” he says.

For example, during one visit to obtain squid, Scott Bennett introduced them to sea robins, an unusual fish with leg-like appendages. , a postdoctoral scientist from Stanford University, was developing sea robins as a genetically tractable system for evolutionary and developmental study at the ǧ����Ƶ. Bellono’s lab has since been using sea robins to study the evolution of novel traits, in collaboration with Herbert.

Bellono has also returned to lecture in the ǧ����Ƶ’s Neurobiology and Neural Systems & Behavior courses.

“This was special to me, since visiting these courses as a college student introduced me to many core concepts that drive our research,” he says.

“I expect we will continue our long-term relationship with the ǧ����Ƶ,” Bellono affirms. “It’s the place that inspired my career in science and continues to shape our curiosity-driven style of research and training.”