Fruit Flies Give Insight into Human Health

Sanford Bernstein spends most of his time in the company of fruit flies, but not without good reason. The San Diego State University distinguished professor of biology has been studying fruit flies for more than 30 years, using the tiny insects as test models to uncover new treatments for human muscle and cardiac diseases.

Now in his third decade of funding from the National Institutes of Health, the Muscular Dystrophy Association and the American Heart Association, Bernstein and his research team are taking on new challenges in their research of the role that mutant myosin genes play in the deterioration of skeletal and heart muscle. What they discover could affect the future of human health.

Bernstein is the recent recipient of two multi-year grants from the National Institutes of Health that total $3.5 million. Since 1983, Bernstein has received more than $16 million in research funding during his career at SDSU which has supported students, postdoctoral fellows and professional staff who carry out investigations on the tiny muscles of fruit flies.

Bernstein and his team look at myosin, the motor proteins that allow the muscles of fruit flies and humans to contract. Fly larvae and pupae are pictured here.

Myosin equals movement

Bernstein’s work revolves around myosin, the motor proteins that allow the muscles of fruit flies and humans to contract.

Bernstein and his team study the different structural and functional properties of the various myosin forms, paying close attention to the defects or mutations in myosin.

Understanding the structure and function of the myosin protein and how it affects muscle structure and contraction in fruit flies helps the research team to better understand it in humans.

Along with a world-renowned team of collaborators, Bernstein has studied genetically altered flies with engineered forms of the myosin protein.

"By creating fruit fly models, our team has gained insight into myosin mutations known to cause human muscle defects," Bernstein said.

"Knowledge of how the variants affect protein biochemistry, muscle structure and muscle contraction may aid in development of both drug and genetic therapies for patients with these weaknesses."

The team is working to better understand forms of distal arthrogryposis — diseases that cause the over-contraction of facial, leg and arm muscles in humans. Muscle diseases like these are caused by mutations in myosin.

By taking the mutated myosin genes that cause the diseases and expressing them in the fruit fly’s flight muscles, the team can create a fruit fly model to simulate a human afflicted with the same muscle disease. They then monitor the fly’s flight ability, the structure of its muscle and the biochemical behavior of the isolated myosin protein to better understand how these diseases affect humans.

For two of the diseases they have modeled — inclusion body myopathy and myosin storage myopathy — the team is in the process of treating mutant flies with drugs and gene therapies to define potential therapeutic approaches that might prove useful in humans. 

Another goal they are working toward understanding is the basis of hypertrophic cardiomyopathy or the thickening on the heart wall in humans. Human myosin mutations can cause this disease.

“We are attempting to reproduce this occurrence in fly hearts so that we can define the molecular defects that result from the abnormal myosin,” said Bernstein.

“By researching the fruit fly heart, our team hopes to have a better understanding of human heart disease and develop some direction toward relevant treatments.”

A legacy of student involvement

Despite his scientific accomplishments and record of successful research funding, Bernstein is most proud of the SDSU students and postdoctoral fellows who have trained under his guidance with the help of his professional staff. Undergraduates have gone on to graduate and medical school and graduate students have attained high-quality postdoctoral and professional appointments.

Four postdoctoral fellows have also remained in the fly muscle field:

• Richard Cripps is a chair of biology at the University of New Mexico.
• Douglas Swank is an associate professor of biology at Rensselaer Polytechnic Institute.
• Anthony Cammarato is an assistant professor of cardiology at Johns Hopkins University Medical School.
• Girish Melkani is a research assistant professor of biology at SDSU.

Bernstein remains in close professional contact with these colleagues. In fact, funds for collaborative efforts on his new grants have been awarded to three of them.