Navigate Up

UPMC/University of Pittsburgh Schools of the Health Sciences
For Journalists
Senior Director
Telephone: 412-586-9764
Communications Specialist
Telephone: 412-647-6190
Patient & Other Inquiries

Pitt Research Yields Insight into the Mystery of Smell 

PITTSBURGH, May 9, 2016 – Researchers at the University of Pittsburgh School of Medicine have uncovered the mechanism underlying a phenomenon in how we smell that has puzzled researchers for decades. In an article appearing online today in the Proceedings of the National Academy of Sciences, the team reports that, surprisingly, the mechanism follows a simple physics principle called cooperativity.
Inhalation of a scent sends a complex mixture of odor molecules swirling toward the back of the nose, where they bind to specialized receptors that are located on millions of olfactory neurons. Activation of these receptors sends signals from the olfactory neurons to the brain, where the smell is deciphered.
Individual neurons have only a single type of receptor and, therefore, recognize only specific odor molecules. However, the hundreds of different types of olfactory receptors are found, or expressed, in approximately equal numbers across the entire population of neurons, which allows a person to detect a wide variety of smells, explained senior investigator Jianhua Xing, Ph.D., associate professor of computational and systems biology, Pitt School of Medicine. Richard Axel, Columbia University, and Linda Buck, now at the Fred Hutchinson Cancer Research Center, received the 2004 Nobel Prize in Physiology or Medicine for discovering the receptors and making these observations.
“Over the past decades, neuroscientists have been trying to uncover how nature accomplishes these two goals: selecting one, and only one, type of olfactory receptor for each neuron, while at the same time ensuring that all receptor types are represented in the whole population of neurons,” said Dr. Xing.
The mysteries of how we smell have generated many experimental observations about how olfactory receptors actually work. In the new study, Dr. Xing and colleagues used these existing experimental data to create a computational model of how olfactory receptor expression can be both uniform across a single neuron, yet very diverse across the entire population of neurons. They then used this model to correctly predict several additional findings that have been demonstrated by other research groups, demonstrating that their model is valid.
Surprisingly, the model suggested a three-pronged regulation of olfactory receptor gene expression that follows a basic physics principle called cooperativity, in which elements in a system influence the behavior of one another rather than function independently. Cooperativity can explain many phenomena, such as the transition between liquid and vapor states, why oil and water do not mix, and even other biological processes such as how a protein folds.
“We are amazed that nature has solved the seemingly daunting engineering process of olfactory receptor expression in such a simple way,” said Dr. Xing.
The findings pave the way for new predictions about how olfactory receptors function that can be tested in future experiments, the results of which will help the team refine their model and make even more predictions.
The research team also included Xiao-Jun Tian, Ph.D., of Pitt; Jens Sannerud , former Pitt undergraduate summer research fellow, currently of Brown University; and Hang Zhang, Ph.D., of Virginia Polytechnic Institute and State University.
This research was funded by National Science Foundation awards DMS-1545771 and DMS-1462049.

©  UPMC | Affiliated with the University of Pittsburgh Schools of the Health Sciences
Supplemental content provided by Healthwise, Incorporated. To learn more, visit

For help in finding a doctor or health service that suits your needs, call the UPMC Referral Service at 412-647-UPMC (8762) or 1-800-533-UPMC (8762). Select option 1.

UPMC is an equal opportunity employer. UPMC policy prohibits discrimination or harassment on the basis of race, color, religion, ancestry, national origin, age, sex, genetics, sexual orientation, gender identity, marital status, familial status, disability, veteran status, or any other legally protected group status. Further, UPMC will continue to support and promote equal employment opportunity, human dignity, and racial, ethnic, and cultural diversity. This policy applies to admissions, employment, and access to and treatment in UPMC programs and activities. This commitment is made by UPMC in accordance with federal, state, and/or local laws and regulations.

Medical information made available on is not intended to be used as a substitute for professional medical advice, diagnosis, or treatment. You should not rely entirely on this information for your health care needs. Ask your own doctor or health care provider any specific medical questions that you have. Further, is not a tool to be used in the case of an emergency. If an emergency arises, you should seek appropriate emergency medical services.

For UPMC Mercy Patients: As a Catholic hospital, UPMC Mercy abides by the Ethical and Religious Directives for Catholic Health Care Services, as determined by the United States Conference of Catholic Bishops. As such, UPMC Mercy neither endorses nor provides medical practices and/or procedures that contradict the moral teachings of the Roman Catholic Church.

Pittsburgh, PA, USA