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Dome - Getting to the Heart of Fruit Fly Research

Dome July/August 2014

Getting to the Heart of Fruit Fly Research

Date: July 8, 2014

Using fruit flies to model human diseases.

Despite earlier skepticism, fruit fly studies have gained traction, says Anthony Cammarato, and offer valuable molecular clues to correcting disease.
Despite earlier skepticism, fruit fly studies have gained traction, says Anthony Cammarato, and offer valuable molecular clues to correcting disease.

“Time’s fun when you’re having flies,” reads the signature on Anthony Cammarato’s emails, borrowing a quote from Kermit the Frog. He would know.

Cammarato, who joined the Division of Cardiology two years ago, directs one of a small handful of laboratories studying the basic mechanisms underlying muscle contraction and regulation of muscle contraction, using fruit flies as models of human disease.

The fruit fly advantage

Both the heart and skeletal muscle of the fly are composed of essentially the same proteins, Cammarato says, and the overall “biosignature” of the muscles’ cells is extremely similar to what’s found in higher animals. The flies offer many distinct advantages—they’re relatively inexpensive, mate and mature quickly, and don’t take up much lab space, plus Cammarato says the animals’ genetics is such that he can introduce designer genes or mutations and get them to express very selectively without disrupting other biological processes. Over the past decade, he has helped develop tools to study different types of muscle function from the level of a single molecule all the way to actual tissue, then integrate the information collected.

While some scientists look at bacteria to clone and express proteins, this is not always possible for components of muscle, he says: “I look at the fly as an extraordinarily sophisticated musclelike bacterium. It allows me to look at and manipulate things in a relatively simplistic manner you couldn’t do feasibly in any other animal system.”

One of his interests is looking for second-site mutations to help correct disease. For example, mating two flies with independent muscle mutations that prevent flight to generate progeny that fly highlights novel interactions among muscle proteins. These genetic screens have the potential to help establish unique approaches to take for higher animals like humans—whether it be drug or biologic therapy.

Cammarato’s lab uses a variety of imaging techniques to study the structural physiology of cardiac and skeletal muscle. The catch is, sometimes the techniques needed don’t exist. In those cases, Cammarato calls on his background in structural biology, working with biomedical engineers, biophysicists and biochemists to build computational software and structural tools needed to analyze their data, often tweaking commercially available equipment to suit their needs.

A new way to study the human heart?

It’s only been over the past five years that the fruit fly heart has gained traction as a viable human model, he says, and there are still quite a few skeptics. The fruit fly heart, after all, is just a slim cylinder powered by two rows of 50 heart cells each—a far cry from the complex organ found in humans. But Cammarato views part of his job as continuing to show how useful the fly is. Ultimately, he’d like to provide some molecular insight into human disease: “The areas of muscle disease we’re studying are so complex. We hope that we can help contribute and fill in some of the holes, especially regarding molecular genetics, to what’s triggering these pathological events and identify modifiers that could help.”

Cardiologist David Kass says Cammarato brings a unique skill set to Johns Hopkins and already has had “lots of people knocking on his door” to express interest in joint research projects. “It’s a very exciting new thing for us to have someone with the interdisciplinary expertise of understanding cardiac myofilament structure and fly genetics, and with the advanced bioengineering techniques to assess what’s been done.”

—Karen Blum

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