Monell: Making Sense of the World

Participants in the Sense of Smell and COVID-19 study receive in the mail a set of scratch-and-sniff odor cards with instructions to perform an at-home smell test, and report their responses and answers to health-related questions on the study’s secure website.

The use of the NIH Toolbox Odor ID Test, an objective measure that directly tests one’s ability to smell a set of common odors, sets Dalton’s study apart from subjective surveys currently in use that rely on a person’s self-reported recall of smell ability. A preliminary study by the Reed lab and others revealed that tests asking participants to directly smell a sample odor reported 70 percent of subjects losing their sense of smell; however, self-report tests showed that only 50 percent of subjects claimed to have an olfactory deficit.

In the rapidly changing environment, technology transfer director Maureen O'Leary, PhD, and Monell scientists are applying these findings to develop a rapid, inexpensive, COVID-19 diagnostic which is currently being tested as a tool for supporting safe return to schools and workplaces.

(Monell resumed in-person human subject research studies under strict safety protocols in August.)

The questionnaire gauges self-reported ability to smell, taste and perceive chemical irritants (sensations like the “cooling” flavor of mint) using qualitative and quantitative measures, before, during, and after COVID-19.

In just over 4,000 participants with confirmed COVID-19, smell, taste and chemesthetic function were significantly reduced compared to their status before infection. The results suggest that COVID-19 may disrupt sensory-neural pathways. They also found that self-reported smell loss was independent of self-reported nasal obstruction (from congestion, for example), which, in common respiratory infections like the flu, can explain temporary smell impairments. Taken together, the preliminary findings confirmed loss of smell as a diagnostic symptom for COVID-19.

Building on this seminal research, Monell President Robert Margolskee, MD, PhD, and Hakan Ozdener, MD, PhD, are using cultures of taste cells in which they can model taste loss from COVID-19. With the goal of determining if cultured human taste cells are susceptible to the novel coronavirus (SARS-CoV-2, severe acute respiratory syndrome coronavirus 2), they will investigate whether the receptor ACE2 and co-receptor TMPRSS2 that the coronavirus uses to enter a cell are expressed in human taste cells or associated cells. They will also study the effect of COVID-19 infection on the viability of taste cells and their ability to replicate, and whether certain sub-types of taste cells are more prone to coronavirus infection.

These solitary chemosensory cells (SCCs) in the gums of mice express several types of taste receptors, along with the taste-signaling molecule gustducin.

Knocking out gustducin in their gum SCCs led to overgrowth of oral bacteria and gum disease, while stimulating bitter taste receptors in SCCs promoted the production of anti-microbial molecules and protected against gum disease.. The team’s findings may lead to personalized dental treatment of periodontitis by harnessing one’s own innate immune system to regulate their oral microbiome.

Developing a reliable early diagnostic has the potential to prevent the deaths of 140,000 women each year, worldwide. Building a diagnostic tool to detect early-stage ovarian cancer by using odor biomarkers in blood was the focus of the late Monell chemist George Preti, PhD, and colleagues at the University of Pennsylvania’s Nano/Bio Interface Center, Ovarian Cancer Research Center, and Penn Vet Working Dog Center. Their work this year brought them one step closer to building an instrument that can detect the odor of ovarian cancer.

All cells release volatile organic compounds (VOCs) that emanate from body fluids and may have an odor. In early studies, the team collected blood plasma samples from ovarian cancer patients, with Preti isolating the unique chemical mixture associated with an ovarian cancer-related odor. The team then demonstrated that dogs can be trained to detect ovarian cancer tissues. In this most recent study, the team tested a nanotechnology prototype instrument against the reliable trained dogs and gas chromatography-mass spectrometry chemical analysis in detecting VOCs emanating from blood plasma of ovarian cancer patients. All three methods showed evidence that plasma from ovarian cancer patients gives off an odor signature that can be distinguished from otherwise healthy individuals.

The research – funded in part by Jade Yoga, the Kaleidoscope of Hope Foundation, the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation, Ms. Bonnie Hunt, Ms. Gail Seygal, and other individuals – points the way toward achieving Preti’s vision of finding the VOCs specific to ovarian cancer and building a “smelling machine” that can instantly detect those chemicals in a drop of blood.  

Watch Diagnosing Ovarian Cancer to learn more about this important work.

The team analyzed volatile chemical metabolites detected in the feces of rabies-vaccinated raccoons and striped skunks and found a link between these volatile chemicals and adaptive immunity in the animals.

Rabies is a zoonotic disease, meaning the virus typically originates in wildlife (such as raccoons, skunks, and bats), moves to domestic animals, mutates, and then is transmitted to humans. Researchers speculate that the novel SARS-CoV-2 coronavirus circulating in bats passed through some other animal and mutated, making it virulent and highly transmissible to humans. Kimball’s latest findings suggest that monitoring fecal volatiles in wildlife and domestic animal scat may serve as an important infectious disease surveillance resource to detect viruses in animals before they make the leap to humans.

One’s liking of fatty foods depends on inborn genetic traits related to fat perception, rather than simply the fat content of the food. Reed and colleagues gave adult identical and fraternal twins attending the annual Twins Day Festival in Twinsburg, OH, a potato chip test. Each participant sampled six types of high- and low-fat potato chips and reported on how fatty they tasted and how much they liked them. Participants also gave saliva samples so their DNA could be extracted for genotyping.

Supported with funding from PepsiCo, Diageo and the National Institutes of Health, the team found that genetically identical twins were more similar in their pattern of liking for the high- and low-fat potato chips compared to fraternal twins. They also identified two specific gene variants that correlated with the twins’ ratings of liking, tying these genes for the first time to the perception of fattiness. The findings show that although fat is almost universally liked in foods, some people may be born with the genetic tendency to prefer foods higher or lower in fat.

Her research showed that inflammation caused by chronic stress shortens the lifespan of taste cells, and the response to acute stress changes the expression of certain taste receptors. What’s more, reduced taste sensitivity can increase an individual’s preference for sugar and salt and may contribute to overeating and obesity. Wang’s findings have practical applications in designing foods and dietary strategies to prevent or balance the negative effects of stress on taste and health.

Childhood is a period of rapid growth and development. While there is variation in the rates of growth among infants, growing “too fast” during the first months is increasingly considered to be a risk factor for later obesity and other diseases. Mennella and her collaborators showed that faster weight gain during the first months accelerated the timing of the infants’ first tooth and the number of primary teeth erupted by their first birthday. Infants who gained weight rapidly also were at greater odds for obesity at one year, but infants who breastfed compared to those who were formula-fed were at lower risk. The timing and patterning of teething may be biomarkers for increased risks for oral and systemic conditions such as obesity and dental caries that may be modified by the type of early diet.

Everyone knows that children love sweets more than adults, but why? In collaboration with former Monell postdoctoral fellow M. Yanina Pepino, PhD, at the University of Illinois Urbana, Mennella studied the relationship between sweet taste preference (concentration of sucrose most preferred) and sensitivity (lowest concentration of sucrose detected). While children require higher sucrose concentrations to detect sweetness (so, less sensitive) and they most preferred higher concentrations of sucrose, sweet taste sensitivity did not predict preference. That both of these aspects of sweet-taste perception – sensitivity and preference – change during development, but are not associated, suggest they undergo distinct developmental trajectories from childhood to adulthood.

In November 2019 Danielle Reed, PhD, co-chaired a Sensory Nutrition and Disease Workshop hosted by the National Institutes of Health to explore these relationships. Multidisciplinary researchers in psychology, neuroscience, and sensory, food, nutrition and health sciences explored how chemosensation influences dietary choice and health.

Several strategies for advancing sensory nutrition research emerged, such as ways to improve chemosensory testing and assessment and how to better define the interplay of chemosensory signals, dietary intake, and metabolism. Attendees agreed that multidisciplinary research teams will move the emerging field forward by establishing connections in big data, neural circuitry, and individual genetics and behaviors. This will help them identify the chemosensory stimuli, receptors, and cell types that contribute to food choice and metabolism. With such information, they can design strategies for mitigating risk for some of today’s most pressing health problems, including obesity, hypertension, type 2 diabetes, heart disease, and cancer.