Creative Models Help Pew Scholars Unlock New Discoveries

Science is a highly creative process in which researchers test innovative methods and models to unlock new findings. This includes the use of model organisms—nonhuman species that help scientists understand complex biological processes and their function in people.

Numerous models are commonly used today, such as yeasts and worms for genetic studies, fruit flies for neurological investigations, and mice for cancer and behavioral research. Chosen for reasons including genetic similarity to humans, ease of maintenance, breeding time, and feasibility of genetic manipulation in a lab, these organisms help make scientific discoveries and medical advances possible.

Three Pew biomedical scholars are taking this type of creativity a step further, using unconventional and unique models to carry out their investigations. From bacteria in cheese rinds to tadpoles and Arctic squirrels, these organisms are helping researchers contribute new insights on bacterial fitness, the neural circuits of infants, and the genetic components that can help guard against oxygen deprivation.

Cheese rinds

Cheese—yes, the popular dairy product—is home to various bacterial and fungal species, also known as microbes, that exist and interact in what essentially is a contained community. Microbes also live in communities within the human body, and their interactions can greatly influence overall health. Cheese can therefore provide researchers with a relevant, simplified mode to study microbial behavior. 

To better understand the activities that take place in a microbial community, 2017 Pew scholar Rachel Dutton, an associate professor at the University of California, San Diego, is using cheese as a model system to examine how microbe species use molecules to communicate with one another. Previously, Dutton mapped the diversity of microbes across more than 130 cheeses from 10 countries. By investigating how certain signals drive the formation, structure, and activity of microbes, she now hopes to uncover how diverse species coexist and how their interactions can affect the community’s vulnerability to disease-causing microorganisms.

Recently, her lab isolated fungal and bacterial species from different cheese rinds to examine how these species interreact. Dutton and her team found that the presence of fungi can influence the availability of important nutrients—such as biotin and iron—to their bacterial neighbors. And that can have important implications for bacterial “fitness,” or how an organism adapts or adjusts to different environmental conditions in order to survive and grow.

Tadpoles

Animal behavior also can offer important clues into human activity. For instance, 2020 Pew scholar Lauren O’Connell, an assistant professor at Stanford University, is working to identify the neural circuits that prompt infants to cry when hungry—one of the earliest forms of social engagement between parents and their offspring, and one that establishes a critical bond.

Poison frogs are among the groups of animals that demonstrate parental care to their offspring in many ways. Tadpoles will beg parents for food, essentially by dancing to communicate their hunger. That trait prompted O’Connell to use tadpoles as a model to better understand the evolution of parental care.

Using an array of tools in neurogenetics and brain imaging, her lab is seeking to determine how the tadpole’s brain processes the need for food and then translates that into a hunger dance. These findings could provide critical insights into an infant’s brain development and contribute to novel approaches to help treat disorders that affect social communication, such as autism.

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Arctic squirrels

Many animals have evolved distinct mechanisms to adapt to cold temperatures. Among those mechanisms is hibernation—when animals lower their body temperature and decrease their breathing, heart rate, and metabolism to conserve energy throughout the winter. For example, the Arctic ground squirrel can hibernate for as long as seven months with a body temperature below zero degrees Celsius, or 32 degrees Fahrenheit. Understanding how Arctic squirrels can withstand and survive long periods of oxygen and blood shortage during the cold months, and the biological mechanisms that help them cope under extreme conditions, could provide clues to treating ischemia, a condition that occurs when the body experiences inadequate blood flow and oxygen levels.

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That’s one reason that 2016 Pew scholar Dengke Ma, an assistant professor at the University of California, San Francisco, has set out to identify the genetic components that provide animals with tolerance to oxygen deprivation. In 2020, Ma’s team identified a variant of the protein ATP5G1 that may help Arctic ground squirrels survive conditions of low oxygen and temperature.

The team discovered that ATP5G1 is present in the mitochondria, the component of the cell responsible for the supply and maintenance of cellular energy. That presence helps to improve the mitochondria’s function and structure when oxygen levels are low. Using the Arctic ground squirrel as a creative model, Ma’s team has been able to inform new strategies to prevent tissue damage from limited blood and oxygen supply, which can happen in strokes and heart attacks.

By studying such uniquely different models, these Pew-funded scientists are able to bring varying perspectives and new insights to the field. Their creative approaches show how research into seemingly unrelated organisms can help to uncover new insights into human health.

Kara Coleman directs The Pew Charitable Trusts’ biomedical programs, including the biomedical scholars, Pew-Stewart Scholars for Cancer Research, and Latin American fellows programs, and Jennifer Villa is a principal associate supporting the programs.