Why Our Noses Are Built the Way They Are?

By Ahmed Barakat, Communications Specialist

From bones to muscles to even fingernails, different body parts evolved to serve different purposes. In other words, there is a logic behind our anatomy: the structure of any system, organ, or tissue allows it to perform its function.

Within the inner ears, for example, there are structures referred to as hair cells. They are built and distributed in a way that allows different kinds to respond to different frequencies of sound. This connection between the distribution of hair cells and their function represents our understanding of some of the anatomical logic behind the auditory system.

When it comes to the sense of smell, however, our understanding of its logic is incomplete. Luis Saraiva, PhD, a principal investigator at Sidra Medicine and an adjunct member of Monell Chemical Senses Center, sought to make better sense of why our noses are built the way they are.

The olfactory mucosa, a region inside the uppermost part of the nose, contains the cells responsible for binding to odorants and initiating a sensation of smell when activated by the binding. These cells are known as olfactory sensory neurons, which contain olfactory receptors, responsible for the detection of odorants.

Humans, for instance, have about 400 olfactory receptor genes. When expressed, these genes produce all the olfactory receptors that allow us to experience the multitude of odors we encounter every day. But unlike what we know about the hair cells of the auditory system, the logic behind the distribution of olfactory receptors within the olfactory mucosa has remained an unsolved mystery.

The motivation behind Saraiva’s recent work was to perform a detailed analysis of how olfactory receptors are distributed along the three axes of the olfactory mucosa of mice. “Think of a map of three dimensions: front to back, top to bottom, and side to side,” said Saraiva.

“Eventually, if you can correlate the distribution of receptors to the physical or chemical properties of odorants, you can get to the fundamentals of the logic of how the olfactory system works and why it is built the way it is,” he added.

The international research team, composed of Saraiva and a dozen more scientists, used spatial transcriptomics and other advanced machine learning techniques to map the spatial distribution patterns of olfactory receptors. For the first time ever, such a map of the olfactory mucosa was produced in three dimensions.

The team also searched the scientific literature to identify as many odorants as possible that had been found to activate certain olfactory receptors. The effort generated the most comprehensive olfactory ligand map to date, comprised of 222 odorants that activate 153 olfactory receptors, adding up to 738 receptor-ligand pairs.

Then it was time for the researchers to investigate any correlations between the properties of odorants and the distribution of their corresponding receptors. Monell’s Joel Mainland, PhD, helped provide an extensive list of all physical and chemical properties of the 222 odorants, including information like the number of carbons or oxygens in the chemical structures of an odorant.

Again, the team employed machine learning to address whether the distribution of olfactory receptors relates to any of the odorant properties. “We came to the conclusion that all of the odorant properties that had a robust correlation with the spatial distribution of their receptors were properties related to how soluble they are in the mucus” said Saraiva.

“In other words, just like a theory from the 1970s had postulated, the olfactory mucosa is like a chromatogram,” he added. For instance, when a drop of ink falls on a piece of paper, it travels across the paper at different speeds creating regions of different shades. Similarly, odorants travel through the olfactory mucosa at different speeds. And in turn, their corresponding receptors are distributed in different zones across the mucosa in a manner that allows for capturing odorants based on how far they can travel.

This innovative study and its findings allowed the research team to put together multiple pieces of the olfactory puzzle. The work provided answers to fundamental questions and supported a decades-old theory with new, robust conclusions. Yet, the journey to a complete understanding of the sense of smell is just in its beginning!