The Five Senses: Smell

August 30, 2017

Neuroscientist Studies How We Perceive Different Scents

Stavros Lomvardas stands in his laboratory with shelves filled with flasks, beakers and other science tools.
Photo by Colleen Deng

It would be unusual to confuse the mouth-watering aroma of baking chocolate chip cookies with the fragrance of a floral perfume or the stench of burning plastic. Most people recognize these scents instantly.

But how did our flexible, adaptive and refined capacity to detect and categorize the myriad scents we encounter each day develop?

That question fascinates Stavros Lomvardas, a neuroscientist at Columbia’s Mortimer B. Zuckerman Mind Brain Behavior Institute, whose work is expanding what is known about the sense of smell. It’s a topic he has researched down to the molecular level, studying how the millions of neurons in the olfactory areas of the brain appear to be identical in the early stages of fetal development and then become sensitive to the chemicals that combine to make different odors.

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“It’s a very complicated system, so it’s a very complicated problem,” Lomvardas said. “When I first learned about it, I thought, ‘This is a problem worth spending my life understanding.’”

Humans perceive a scent when a specific chemical enters our nostrils and reaches specialized tissue in the roof of the nasal cavity. Known as the “olfactory epithelium,” this tissue is shot through with thousands of receptors, each made of a protein that will bind only with a specific chemical. When the chemicals that comprise a scent come along, each one fits into a receptor like a key into a lock. The receptors then send signals to a brain cell, or neuron, which fires and allows us to perceive a particular scent.

Lomvardas didn’t start out studying how the sense of smell works. A native of Icaria, a small Greek island, he was fascinated by the human immune system while attending college in Crete. He came to the United States in 1998 to earn a Ph.D. in biochemistry at Columbia, and set to work on his thesis by trying to understand what happens inside cells when they are infected with a virus.

That topic led Lomvardas to Richard Axel, a Zuckerman Institute co-director who was awarded the 2004 Nobel Prize in Medicine for his pioneering research on the workings of the olfactory system. Lomvardas didn’t know much about Axel’s work on smell, but knew of his older work in molecular biology and immunology, when in 1999 he asked Axel to serve on his thesis committee.

“During our interactions in these committee meetings, I realized how brilliant he is,” Lomvardas recalls. “So I started reading more about his current work as a neuroscientist, and through his papers I realized the beauty of the olfactory system.”

There are roughly 1,000 different olfactory receptor genes, and as many receptors. How one gene is activated to allow a neuron to detect a chemical present only in bananas, for example, and the gene next to it is activated to allow a neuron to detect the scent of cherries is the mystery Lomvardas set out to solve.

All cells carry the same DNA, but unique combinations of proteins in the nucleus of each cell control which genes will be “turned on” determining whether the cell will become part of the ear, the eye, the nose or any other part of the body.

Working with mice and imaging techniques available only recently, Lomvardas has discovered a unique and mysterious phenomenon. At a certain point in fetal development, the olfactory receptor genes in the nucleus form two or three compartments so densely packed that no gene can be turned on. But a single gene eventually “pops” out and moves to another part of the nucleus, where it usually enters another unique structure that causes it to pump out copies of an olfactory receptor that recognizes a specific scent. The thousands of olfactory receptor genes remaining in the compartment are viewed as junk DNA by that cell and ignored.

The exact sequence that determines which gene pops out is part of the mystery that Lomvardas is still exploring. Only time, and more work in the lab, will provide answers.

“I like to understand the mechanism by which things happen—the uncharted territories, the processes where you know that something very unusual is taking place, but you don’t have a prior explanation of how it is happening,” Lomvardas says. “To me this is the most intriguing part in science, when you go into a problem and you don’t have a clear hypothesis.”

—By Adam Piore