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

Nicholar Bellono
Nicholas Bellono

“The MBL 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 Current Biology.

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 MBL

“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.”

Nicholas Bellono, then an undergraduate, doing experiments with Heather Eisthen at MBL in 2010.
Nicholas Bellono, then an undergraduate, doing experiments with Heather Eisthen at MBL in 2010.  Credit: Marine Biological Laboratory

Then an undergraduate at Michigan State, Bellono came to Woods Hole through Heather Eisthen, 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 MBL in 2014, specifically to the summer lab of Liz Jonas 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 MBL in squid axons by Liz Jonas.”

Liz Jonas’ pipette-within-pipette technique for measuring electrical activity inside organelles inside cells.
Liz Jonas’ pipette-within-pipette technique for measuring electrical activity inside organelles inside cells. Credit: Nicholas Bellono

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 MBL spirit of trying a bunch of stuff until something works, after visiting Liz, I went to the lab of Dejian Ren (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 characterizing the first melanosome ion channels 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 David Julius 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 MBL.

A little skate shipped from MBL to UCSF.
A little skate shipped from MBL to UCSF. Credit: Duncan Leitch

“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 Ricardo Arenada (University of Maryland), now co-director of the MBL Neurobiology course, suggested skates.

Bellono worked with Scott Bennett and the late Dave Remsen of the MBL 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.”

Skate electroreceptors imaged at UCSF.
Skate electroreceptors imaged at UCSF. Credit: Nicholas Bellono

Bellono, Duncan Leitch (former MBL Grass Fellow, now at UCLA), and Julius published their findings in 2017 and 2018 in Nature.

Nature magazine cover titled "Body Electric" with Little Skate.

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 Harvard Magazine. “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.

Cephalopod mariculture tanks at the Marine Biological Laboratory.
Cephalopod mariculture tanks at the Marine Biological Laboratory. Credit: Tom Kleindinst

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 MBL and the New England Aquarium for advice about setting up a seawater facility in Cambridge (not exactly typical) and learned that the MBL had recently established a cephalopod facility! That was super exciting because MBL 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.”

Bret Grasse in the Cephalopod Mariculture Facility at the MBL.
Bret Grasse in the Cephalopod Mariculture Facility at the MBL. Credit: Megan Costello

In 2020, Bellono’s lab reported 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 two studies in Nature 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.

Nature magazine cover titled 'Acquired Taste" with Octopus.

Back at the MBL, 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 MBL to obtain specimens or for longer-duration experiments. “And, perhaps most true to the MBL 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. Amy Herbert, a postdoctoral scientist from Stanford University, was developing sea robins as a genetically tractable system for evolutionary and developmental study at the MBL. Bellono’s lab has since been using sea robins to study the evolution of novel traits, in collaboration with Herbert.

Bellono with then-MBL Neurobiology course director Diana Bautista (UC Berkeley) in 2019
Bellono with then-MBL Neurobiology course director Diana Bautista (UC Berkeley) in 2019, when he lectured in the Neural Systems and Behavior course. Credit: MBL Neurobioogy Course

Bellono has also returned to lecture in the MBL’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 MBL,” Bellono affirms. “It’s the place that inspired my career in science and continues to shape our curiosity-driven style of research and training.”