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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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