Unraveling a Cellular Mystery
By Matt Windsor
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Once dismissed as the cellular equivalent of tonsils, primary cilia are now known to be invaluable antennae that help cells sense their environment. UAB's Bradley Yoder has helped connect primary cilia with a host of human ailments, from kidney disease to obesity and even cancer. At top, primary cilia (colored green and red) protrude from renal epithelial cells grown in culture. |
In cell biology, as in love, you often don’t know what you’ve got till it’s gone. For more than a century, scientists have known that most cells in the human body come equipped with an odd projection on their outer surfaces called the primary cilium. Unlike the wavy, hairlike cilia you may remember from biology class—the ones that sweep mucus out of the airways—the primary cilia are rigid and didn’t seem to have any useful function. They were written off as vestigial, like tonsils or the appendix.
But 10 years ago, a handful of cell biologists including UAB’s Bradley Yoder, Ph.D., began to unravel the secrets of this obscure organelle. Starting in green algae and only lately moving up to humans, they made a startling discovery: If a cell loses its cilium, bad things begin to happen. Their investigations have revealed that, far from being an artifact, the primary cilium is actually an important communications device—and a major player in human growth and development, kidney disease, obesity, wound healing, and even cancer.
“Human patients with ciliary defects are often blind, they can’t smell, and they have difficulty hearing,” says Yoder. “It turns out that the cilia are loaded with receptors and channels that allow a cell to sense its environment and communicate with that environment.”
Cilia in the embryo help determine the overall body plan, including the key directive to put the heart just to the left of the centerline. (One genetic defect in the cilia causes people to be born with a completely reversed body plan, says Yoder: “Everything’s on the wrong side.”) Cilia on the rods and cones of the eye gather and respond to light. Cilia in the nose sense and react to odors. Primary cilia are involved in so many sensory functions, Yoder says, that they have earned the name “the antennae of the cell.”
Messaging the Immune System
By Troy Goodman
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The powerful immune system protein IL-21 acts as a molecular go-between to help the body's infection-fighting CD4 and CD8 T cells accomplish their missions. |
It’s true of any defensive force, from the military to microbiology: Communication is key to coordinating a successful attack on invaders. A recent breakthrough by UAB researchers could help improve that cross-talk among cells, giving the body’s natural defenses a fighting chance against deadly chronic infections like human immunodeficiency virus (HIV) and hepatitis C, says Allan Zajac, Ph.D., an associate professor in UAB’s Department of Microbiology.
Previously, scientists had been at a loss to explain how two different T cells worked in tandem—the CD4 T cells that help the immune system know when to attack (“helper T cells”) and the CD8 T cells that do the actual virus killing (“killer T cells”). Any successful communication between the two would require a good messenger molecule; in a study published in the journal Science, Zajac and his UAB lab report that messenger is the powerful immune system protein interleukin-21 (IL-21).
IL-21 is a molecule made by CD4 T cells, Zajac explains. “And one of the hallmarks of HIV infection, for example, is that your CD4 T cells go away. So they cannot make the normal array of helper molecules. After identifying IL-21, we gave it to mice that lacked CD4 T cells, and it improved their immune responses. If we add IL-21 to a human immune response, the results might be similarly impressive.”
The human body already makes IL-21, Zajac notes, but its levels may be insufficient under certain circumstances. IL-21 is thought to have a lot of beneficial effects, including helping T cell and antibody responses, Zajac says. He also suggests that IL-21 may be the missing link that keeps T cells from becoming exhausted or depleted during the long battle against a chronic invader like HIV. But he adds that better understanding of IL-21 comes with a caution—this powerful protein may have its own side effects, beyond infection problems, that would require physician monitoring.
Zajac says that research teams outside Alabama have looked at IL-21 responses in cancer biology, for example, with positive results. Seattle-based ZymoGenetics Inc., which is testing a commercially viable IL-21 agent unrelated to UAB, reports that the molecule likely could serve as an immunity booster when administered with chemotherapy or as a single-agent cancer killer.
Further IL-21 research is moving forward at UAB. Zajac has proposed a study that would restore IL-21 to normal levels in a model of HIV infection to see if it boosts the body’s antiviral attack.
This article originally appeared in UAB Medicine, the magazine of the UAB School of Medicine.
Research Fair Spotlights Student Discoveries
By Claire L. Burgess
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Harry Miree captured the sounds of more than 50 copy machines for his latest project. To see how he turned those sounds into a cohesive tune click here. |
You don’t have to have a doctorate—or even a college degree—to work on groundbreaking research at UAB. At a time when most freshmen are still trying to find the dining hall, Ashleigh Allgood was digging up fresh insights as part of a horticultural therapy research project. Junior Nathan Renneboog followed his interest in epidemiology into outer space. And senior Jennifer Ghandhi traveled to Florence, Italy, to present her research on happiness and health.
Those projects and many more were featured at the second annual UAB Expo. According to Christopher Reaves, Ph.D., director of UAB’s Office for Undergraduate Research and the event’s creator, the Expo does more than give students the opportunity to showcase their research and field work. Undergraduates can network with faculty members and other students as they explain their projects, respond to questions, and garner feedback, Reaves says. The whole experience helps deepen the understanding of their work and gives them valuable public-speaking experience, he explains, which is a mainstay of graduate education and professional life.
Spreading the Word About Student Research
By Caperton Gillett
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The third edition of Inquiro debuts this month. Each issue features student art on the front and inside covers (click image for larger version) |
In 2007, junior chemistry major Suzanne McCluskey looked up from her lab bench and made a scientific observation: Motivated undergraduates at UAB had plenty of opportunities to conduct meaningful research but few outlets in which to share their results with the world. So she set about creating one.
McCluskey assembled an all-undergraduate editorial board, established editorial policies, and then made her case to Lowell Wenger, Ph.D., then dean of the School of Natural Sciences and Mathematics (now part of UAB's College of Arts and Sciences). Wenger readily offered his support, funding the necessary computers, printers, and software, and University Honors Program director Mike Sloane, Ph.D., provided an on-campus location for the enterprise. Everything else was left up to McCluskey and her team of fellow students.
Thus Inquiro was born—a full-color, 80-page undergraduate research publication that rivals the production values of many national scientific journals. Each edition of the annual journal—the third issue debuts this month—represents thousands of hours of effort on the part of the editorial staff, faculty reviewers, and undergraduate students who conduct the research and shape it into articles to share with their peers.
Solutions for Distracted Driving
By Bob Shepard
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A few weeks ago, a woman in upstate New York died when her car collided with a tractor-trailer. Not long before, a Texas teen was killed when her station wagon ran into another truck. Each driver was under the influence—not of alcohol, but of the glowing screens of their cell phones. Both women were texting while driving when the crashes occurred.
Those chilling tales were part of the keynote address given by United States Secretary of Transportation Ray LaHood at the Alabama Distracted Driving Summit in Birmingham in early December. The summit was the first statewide response to LaHood’s call for a national debate on distracted driving—a practice he paints with the same brush as drunk driving.