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'Mucus Hurricane'

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Pursuing Disease Across All Boundaries

Imagine scientists who turn themselves into “actors” in their experiments within the human cell in an effort to fight disease. Sounds like a movie plot, doesn’t it?

It’s a reality at Carolina, where researchers are using small tools to study the forces that make lungs expel pathogens, and also are working on three-dimensional technology that will make it seem as though scientists are inside cell cultures to experience how lungs work.

Throw in a subplot about these researchers pursuing disease across all boundaries and disciplines. Now there’s thrill-a-minute action. Much of the action involves Carolina undergraduates training with scientists in many departments to solve problems in collaborative ways that will enable them to enter groundbreaking careers.

For example, in the Virtual Lung Project (VLP), students and faculty in applied sciences, applied mathematics, chemistry, computer science, physics and astronomy, the School of Medicine have teamed with Dr. Richard Boucher and the Cystic Fibrosis Center. This team of researchers is modeling the properties of lung fluids and discovering how fluid biochemistry, composition, and structure determine those properties. The research will result in a better understanding of how a lung’s beating cilia and air flow cause mucus to remove bacteria and environmental toxicants from our bodies.

The lung defends itself with a thin (10 - 50 μm) liquid layer that is organized into mucus and periciliary liquid components. The synchronized beating of cilia, a seven-micron long complex of 4,000 molecular motors, propels the mucus. Underneath the mucus, a periciliary liquid layer allows cilia to beat effectively in a low-viscosity solution. Failure of this system leads to bacterial infections and death, so VLP researchers are committed to sharing knowledge and expertise so they can eventually stop cystic fibrosis.

“This is the future of scientific collaboration,” says Greg Forest, a professor leading the applied mathematics scientists. “Our students have opportunities to work across disciplines. In the group’s fluids lab, students can develop a specialization and expertise while conducting research as part of a larger effort. This new model for doing science and health will enable students to spend their junior and senior years working intensively on research. There are long careers ahead for students who get involved in collaborative research.”

On any given day applied mathematics faculty and students work on complex fluids, hydrodynamic flows and mixing phenomena, biochemical network, and multiscale modeling. Professors Roberto Camassa and Richard McLaughlin in applied mathematics bring fluid mechanics to the VLP model. They are modeling the proteins that put cilia into motion, the superstructure of beating cilia, and the flowing and mixing of mucus.

On the simulation side, mathematics professor Tim Elston uses a stochastic model of the 4,000 motors inside cilia arranged in a mechanical structure derived from high-resolution electron microscopy studies. The motors drive the cilia through a calculated pattern that can be compared with experimental shapes measured on living cilia. Two other mathematics professors, Sorin Mitran and Mike Minion, calculate the fluid flow coupled with the cilia. Their simulations can then be compared with the cell culture experiments.

From chemistry, professor Michael Rubinstein’s experience in polymer physics is contributing models of how the properties of mucus arise from the molecular constituents.

And, for over a decade, the Computer Science Department and the Department of Physics and Astronomy have collaborated to create nanoscience tools. The latest system allows a researcher to use a force feedback pen to maneuver a magnetic bead inside live cell cultures. By attaching magnetic beads to cilia, scientists experience the forces that live, beating cilia generate to propel mucus.

“Our next generation system will incorporate three-dimensional microscope imaging and 3-D rendering to place the scientist inside the cell culture as an actor in the experiment,” says physics professor Richard Superfine. “Disease knows no disciplines. We need to train students who will pursue the intellectual challenge of disease across departments and campuses.”

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