Department News

A Mechanistic Approach with Nicholas Bellono

A Mechanistic Approach with Nicholas Bellono

MCB’s new assistant professor, Nicholas Bellono, has an eye for detail. In his sensory biology lab, students will be encouraged to figure out how cells respond to stimuli, not just why or when.

“I encourage students to understand how single proteins work, how they contribute to a cellular system, and how such molecular functions impact the organism,” he said.

Bellono’s new lab is devoted to researching molecular mechanisms of sensory biology. How do organisms perceive sensory signals, and what does this say about the evolution of those organisms? The focus for now will include ‘signal transduction and amplification, ion channel biophysics, and sensory adaptation and evolution,’ but the driving force will be pure research and individual curiosity.

“We are thrilled that Nick joined MCB and Harvard this year,” said MCB Chair Venki Murthy. “He is a wonderfully creative scientist, whose research is driven by an infectious curiosity.”

“I think the most important thing for me is to emphasize that students study problems that they are truly interested in and curious about, which to me is the best part about being a scientist,” Bellono said. “And in doing so that they take a mechanistic approach in their science, and really try to understand how something works at a detailed level.”

“I’m a huge fan of Nick Bellono’s research,” said MCB professor Florian Engert, whose lab shares a hall with Bellono’s. “It is remarkable how he transitions effortlessly from the basic molecular properties of individual channels and receptors to adaptive behavioral principles at the level of whole organisms.”

Bellono began his academic journey at Michigan State, and completed his graduate work at Brown University with Elena Oancea and Anita Zimmerman. He went on to postdoctoral work at the University of California, San Francisco (UCSF), where he worked with David Julius. It was in college that he first realized that students could work in labs.

“So I thought that sounded like a wonderful job,” he said. “I started working with Heather Eisthen, who studies olfaction in salamanders and how their behavioral state affects their sense of smell. I’ve been fortunate to have fantastic mentors throughout my training, including Heather who introduced me to neuroethology, sensory biology and electrophysiology, which remain major focuses of my research.”

Bellono was especially enamored of the mechanical aspects of research. He enjoyed figuring out how to set up the physical elements of the experiment to get the right readings almost as much as the actual data at the end.

“In most cases we spent our time trying to optimize the system and get good recordings,” he said. “I really like physiology experiments because they are an interactive process. When you do something to the prep, in that case we applied odorants, and you see the results in real time. Then you get to go back and try something different based on what you saw, so it’s sort of this back and forth process.”

After completing his work at Michigan State and the Marine Biological Laboratory with Eisthen, Bellono moved on to graduate school, planning to continue with research on synapses and neuron communication. His PI convinced him to try another lab rotation, and encouraged him to work in skin.

“I thought I was about neuroscience all the way,” Bellono said. “But I ended up working on skin by applying neuroscience-based methods to measure ion currents in skin cells, and studied their contribution to pigmentation. It was a nice, reductionist, clean readout – the cells were either pigmented or not, and I was investigating how these ionic mechanisms gave rise to that.”

This work produced several papers, including one in 2014 titled “An intracellular anion channel critical for pigmentation.” In it Bellono and the other members of Elena Oancea’s lab discussed the role of the protein OCA2 in melanin production, noting that defects in this protein account for one of the most common types of albinism.

Albinism is characterized by lowered production of melanin, which is made and stored in the melanosome cellular organelle. The Oancea lab’s paper proposed that OCA2 is involved in the ion channel responsible for moving chloride ions across the organelle membrane, which is one key step in melanin production. They tested this using patch-clamp recording techniques, which allows researchers to measure ion currents in individual organelles.

After his work at Brown, sensory biology was the next logical step – combining his new interest in ion channel biophysics with his old interest in neuroscience.

“What I like more than the initial discovery is finding out the mechanisms by which that observation occurs,” he said. “And that’s why I’ve been drawn to sensory transduction, because its tractable in that you have a stimulus, you know the input, and then how do you get the output? What are the mechanisms by which that occurs?”

When he moved to UCSF he not only found a new, exciting direction for his curiosity, but he also came to an interesting realization.

“The most exciting part of my postdoc for me was learning to combine my interests in neuroethology and ion channel biophysics in ways that didn’t constrain me to working with standard model organisms,” he said. “In my postdoc, we investigated many different systems to find those which were most appropriate for our research questions. In this regard, our studies on how sharks and skates sense electrical fields were really different for me and really fun.”

His work with sharks and skates extended to studying sensations in the gut. Throughout this research, Bellono got to work on his favorite part of the process – figuring out how to do the prep work, how to optimize the system for running experiments, and how to measure the results.

“In graduate school the hurdle wasn’t isolating specialized cells, but we actually went inside the cells and had to isolate these specialized organelles,” he said. “So again, we were leveraging a unique system to learn new biology but first had to figure out how to make the prep to obtain the necessary measurements.”

At UCSF and now at his new lab, one of Bellono’s avenues for research is the ampullae of Lorenzini – which are electroreceptors found in sharks, skates, and some other cartilaginous fish. A couple of the papers he produced at UCSF, including one that made the cover of Nature for June 2018, dealt with these intriguing receptors.

Nick Bellono faculty profile, Bellono lab website

by Mary Parker