Prof. Masha Niv of Hebrew University is one of the world’s experts on bitterness.

At the university’s Institute of Biochemistry, Food Science and Nutrition, Niv and her lab have created BitterDB, the most comprehensive online database of bitter-tasting molecules and their receptors.

The open database, listing more than 2,200 bitter molecules, uses machine learning and computational analysis to help scientists around the world predict bitterness without ever having to taste it.

One of the lab’s goals is to figure out how to mute bitter tastes, making it easier for children, people with disabilities, the elderly, and even animals to swallow bad-tasting medicine.

Niv told The Times of Israel that she finds it interesting that, on Passover, when Jews eat maror, or bitter herbs such as horseradish, to ritually remember their ancestors’ time as Egyptian slaves, they are not avoiding bitterness but “leaning into it.”

“Perhaps we eat bitter herbs not to feel sorry for ourselves but to remember that bad things happened and remind ourselves that we’ve survived,” Niv said. “Maybe it’s a way of thinking about resilience.”

Niv then segued into her latest peer-reviewed research, published on Tuesday in Cellular and Molecular Life Sciences. Written by graduate student Nitsan Dallal, the study shows a new way to block the body’s bitter taste receptors, which are the sensors that detect bitterness.

That means that the bitterness of maror — or any other bitter substance — can be stopped from inside the receptor, before the bitter molecule triggers a signal to the brain.

The findings can pave the way not only for better-tasting medicines but also can help further the understanding of the biological roles of bitter taste receptors that appear outside of the tongue. They’re even found in tissues such as the lungs, heart, and brain.

Bitter doesn’t necessarily mean toxic

For years, people believed that tasting bitterness helped people survive because the bitter “warned you not to eat poison,” Niv said.

“The thinking was, you taste something bitter, and you die,” she said. “I said, ‘Okay, let’s try to look for data that shows an agreement between the levels of toxicity and bitterness.’ And we found that many health-promoting molecules are actually bitter.”

Indeed, dark leafy greens such as kale and arugula are classic examples of bitter foods that are rich in antioxidants. Other healthy but bitter foods include Brussels sprouts and broccoli.

Dark chocolate and coffee are also bitter, and yet they turn out to be “good for you,” Niv said. “Studies linked moderate consumption to lower rates of heart disease and diabetes.”

“The bitter taste is not necessarily toxic, but rather warns you from something unknown or novel,” she explained. “If anything, the stinky smell has a better correlation with toxicity than bitter taste. That makes sense, right? Because if you’re already eating it, then maybe it’s already too late.”

Niv had no background in food science or taste science before joining the Hebrew University as a faculty member.

“I was trained in theoretical chemistry and then computational biology,” she said. “I worked in a biotech drug discovery startup, and the drug aspect was always interesting for me.”

She got her taste for taste when she started her position at the Institute of Biochemistry, Food Science and Nutrition.

“I was looking for something that would be relevant for my department and also interesting for me,” Niv said. “I was also inspired by Professor Micha Naim’s work on taste, and fascinated by the complexity of the bitter receptors.”

Taste buds are not just simple bumps on the tongue. Rather, they are clusters of about 50–100 specialized cells that work like a molecular lock-and-key system, Niv explained. After taking a bite of a clementine, for example, saliva dissolves the food and releases thousands of tiny molecular “keys” that float around the mouth.

Scientists recognize five basic tastes: sweet, salty, sour, bitter, and umami (also known as savory).

To perceive a taste, one of those molecular keys must find its way to a matching cellular “lock,” a receptor protein that sits on the surface of a taste cell, shaped to recognize specific molecules.

When the right molecule fits into the right receptor, it triggers a chain of chemical signals inside the cell that eventually travels to the brain, where the taste is perceived.

The traditional scientific view was that bitter taste receptors had a single keyhole facing outward on the side of the cell exposed to the mouth. Once a bitter molecule docked into this outer pocket, the receptor changed shape, setting off this cascade of signals.

“How can the receptors of humans or other animals recognize so many chemically different molecules?” Niv said she began to wonder.

Investigating TAS2R14

In 2000–2001, as part of the wave of discoveries enabled by the Human Genome Project, scientists identified a previously unknown family of genes dedicated entirely to detecting bitterness.

The human genome, it turned out, contains 26 functional genes for tasting bitter compounds, “a surprisingly large number that reflects just how important bitterness detection has been to our survival as a species,” Niv said.

What this means is that instead of needing a unique sensor for every bitter leaf, berry, or chemical on the planet, these 26 receptors can each recognize a range of molecular shapes, alerting the brain to a potential danger before it is swallowed.

One of those genes codes for the TAS2R14 receptor, Niv said, which has “extraordinary versatility.”

Like a master key reader, she said, this receptor can detect hundreds of structurally different bitter compounds, making it one of the most broadly-tuned sensory receptors known in humans.

In 2024, Niv’s lab was among the first groups worldwide to solve the three-dimensional structure of TAS2R14 using cryo-electron microscopy. The Jerusalem research team found a previously unknown pocket hidden inside the cell about the same time as several other international research teams.

This meant there was another way for bitterness to get tasted, not just from the outside but, as Niv explained, “inside out.”

Discovering TAS2R14 in other parts of the body

Bitter taste receptors, including TAS2R14, have also been found on cells lining the lung airways, where they act as sentinels.

When bacteria release bitter-tasting chemicals during an infection, these receptors detect them and signal the airway muscles to relax and open up, which is a natural defense response that improves breathing.

Niv’s latest research, led by graduate student Dallal, has now shown that the TAS2R14’s second pocket on its interior face can be used not only to switch the receptor on, but also to switch it off.

This two-sided control can be used to block the bitterness of a drug, for example, and also to activate the receptor to open airways in the lungs.

“The findings point to a new generation of precisely targeted drugs,” Niv said.

Researchers hope this finding could eventually contribute to treatments for respiratory conditions such as asthma and COPD.

“It could also make life easier for patients who struggle to swallow bitter-tasting medication,” Niv said.

These applications are still in early stages of exploration.

Niv’s lab’s website has gathered data about bitter molecules from humans, mice, chickens, and cats, to help study everything from “how to make better-tasting coffee to how to treat diabetes,” she said.

The Times of Israel contacted two researchers at the Monell Chemical Senses Center in Philadelphia who were not involved in Niv’s research. The research institute is dedicated to the scientific understanding of taste and smell.

“BitterDB exemplifies how well‑organized, openly accessible chemosensory data can unlock the power of AI for flavor, food, and health in a standardized way,” said Valentina Parma, Assistant Member & Senior Director of Multisector Engagements at the center.

If a pharmaceutical company develops a medicine that tastes awful, Niv explained, it can use the database to pinpoint which of the human bitter receptors the medicine triggers. Scientists can then design the appropriate blocker to barricade the bitter from reaching the brain.

“Niv’s work has taught us, at the cellular level, how to block bitterness, with practical applications such as making foods tastier or medicines easier to swallow,” said Danielle R Reed, Ph.D., the Chief Science Officer and Member at the center.

Reed pointed out that the database is unique worldwide, making it the world’s go-to resource on bitterness.

This seems ironic because Niv is not a gloomy person. She said that she found it fitting to study bitterness around Passover time.

“We eat maror to remember hardship,” Niv said. “To really feel it, not just recall it. And we do this science in the hope that one day, the bitterness of illness will be easier to bear.”

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