What Can We Learn From a Fruit Fly?

When Grace Dr. Zhai, Ph. D., first arrived at the University of Miami Miller School of Medicine in 2007, a security guard refused to let her into the building.

Dr. Zhai, a molecular and cellular pharmacology professor, was trying to unload 80 boxes filled with live fruit flies from her minivan. The guard assumed she was in the wrong place and directed her to the Division of Veterinary Resources. It took a frantic call to the chair of her department to get Dr. Zhai into the building.

“Nobody had ever heard of fly research here,” she said. “I came into a void.”

In her first months, Dr. Zhai alternated between feeling like a circus curiosity and an office-wide annoyance. Some colleagues would excitedly approach to see the flies they’ve heard about, while others angrily marched over whenever they found a fly buzzing around their office. She struggled to find a vendor to supply the cornmeal, molasses, and yeast needed to cook up batches of fly food. She pleaded with building officials to install temperature controls for her sensitive flies and felt isolated as the only fly researcher in South Florida.

“There was no fly community,” Dr. Zhai said.

Fifteen years later, things have changed.

The self-professed “fly lady” runs a nine-person lab featuring 100,000 fruit flies. She has become the senior associate dean for basic science research at the Miller School and has used her flies to expand the understanding of a wide range of human neurological diseases.

What can fruit flies teach us about humans?

Drosophila, the scientific name for fruit flies, have fascinated researchers for over 100 years because of their complex structures and short life cycles.

Their 100-day lifespan allows scientists to study generations of changes in relatively short periods.

Fruit flies became even more popular as scientists began decoding genetic sequences.

The fruit fly genome was fully decoded in 2000, allowing scientists to tweak each of the 13,600 genes in its body. They realized that 75% of the genes in its nervous system are homologous to human genes, meaning they have a similar shape, function, and purpose as human genes.

Fruit flies also share the same circadian rhythm as humans – awake by day, asleep at night. And while humans are vertebrates, meaning they have a spine, and fruit flies are invertebrates, meaning they have an exoskeleton but no spine, Dr. Zhai points out that the human head is closer to that of an invertebrate.

“You have the shell on the outside and the soft bits on the inside,” she said. “From neck down, we’re different. But neck up, we’re the same.”

All those similarities have allowed Dr. Zhai to study the genes of fruit flies to understand and develop treatments for human neurological conditions.

“You can study the normal function of something to death, and that still doesn’t tell you the reason for many of the diseases,” she said. “To really get to the root cause of disease or how the brain works, you need to understand its genetics.”

What have we learned from the study of fruit flies?

Dr. Zhai and her team have now used that process to study common human afflictions that remain difficult to solve, including deafness, brain tumors, and Alzheimer’s disease.

She has been able to study rare afflictions like Snyder-Robinson syndrome, Huntington’s disease, and Charcot-Marie-Tooth disease. They have learned how humans are affected by blue-green algae that is increasingly common along Florida’s waterways as well as sugar substitutes people use in their morning coffee.

One of Dr. Zhai’s biggest accomplishments has been her work with the National Institutes of Health (NIH) on a project to diagnose rare, undiagnosed diseases.

As gene sequencing became more accessible, a team of scientists at NIH was determined to help patients who visited doctor after doctor but couldn’t figure out what was wrong with them.

Dr. Zhai offered up her fruit flies as a way to help.

She took the gene sequence of the affected human and altered her fruit flies to mirror the problem. By running tests on generation after generation of fruit flies, she would be able to determine if that gene was indeed the problem.

What is the Undiagnosed Disese Network (UDN)?

That initial work identified four new diseases and one new variant.

It also established a uniform system to conduct investigations en masse. The work led to the creation of the UDN, which — to keep up with the demand — has expanded to more than 10 institutes and universities around the country.

“The UDN has benefitted many families,” Dr. Zhai said. Knowing what disease they face has comforted those families, “but you want to do something about it.”

Dr. Zhai has also focused on finding treatments to the diseases she studies.

In one case, her team identified the metabolic problem that leads to Snyder-Robinson Syndrome (SRS), a rare disease that only affects boys in fewer than 100 families worldwide.

Using her fruit flies, Dr. Zhai determined that SRS was thriving in patients partly because of a buildup of a toxic metabolite in their system: hydrogen peroxide. She started treating her affected fruit flies with antioxidants and saw immediate success.

Humans infected by SRS started using the antioxidants, and some saw drastic improvements in their physical, speech, and cognitive functions.

That work earned her the Snyder Robinson Foundation’s 2019 award for outstanding researcher. And it was another example of people realizing the full potential of Dr. Zhai’s flies.

“They can never look at flies the same way again,” she said.

Dr. Zhai and her flies continue to forge ahead.

She is currently studying:

• how sleep disruptions compound Alzheimer’s disease
• how copper in the environment affects people with Huntington’s disease
• is helping the rare disease consortium in the European Union develop its own version of the rare disease identification network

And after many long years of toiling in solitude, she is no longer alone. The College of Arts and Sciences at UM and several South Florida universities have hired fly researchers, and they banded together, even holding an annual conference called “Flies on the Beach.”

Finally, she has her community.

“Like flies, we like to cluster,” she said.

Alan Gomez is a contributing writer for UMiami Health News.

Tags: basic science research, Dr. R. Grace Zhai, Miller School of Medicine