A Summer Mystery, with a Twist

If you were to unwind the DNA in a single human cell, it would be about six feet long. Do the same with all of the DNA in your body, and it would be twice the diameter of the Solar System.

How does it all fit? By coiling and twisting itself into an incredibly compact shape, DNA squeezes itself into the cell nucleus. But it can go too far, winding itself into a “supercoil” so tight that the DNA strand can’t be unzipped for normal replication or transcription. That’s where special enzymes called topoisomerases come in; they catalyze the relaxation of these supercoils and allow the DNA to resume normal function. In fact, topoisomerases are so important that a class of anticancer drug, known as camptothecins (CPT), kills fast-dividing cancer cells by targeting DNA topoisomerase 1, also known as Top1.

How does that work, exactly? Scientists aren’t sure. But Marina Triplett, a rising senior from Athens, Alabama, will spend her summer trying to find out. Triplett, who is majoring in biochemistry in the UAB College of Arts and Sciences, is one of 10 UAB undergraduates selected for the inaugural President’s Summer Research Scholarship Program. The students received $4,500 stipends and are devoting 30 hours per week for 12 weeks to research. They will present results at the Summer UAB Expo in August.

“Previous studies suggest that the binding of CPT selectively slows the removal of positive supercoils in DNA by Top1, leading to an increase in positive supercoils,” said Triplett, a member of the UAB Honors College’s Science & Technology Honors Program. (“Positive” supercoils are overwound; “negative” supercoils are underwound.) “By understanding the mechanism of how CPT kills a cell, it may be possible to increase the effectiveness of drugs derived from CPT or understand which compounds may work in combination therapy.”


10 UAB undergraduates selected for the inaugural President’s Summer Research Scholarship Program received $4,500 stipends and are devoting 30 hours per week for 12 weeks to research.


For the past two years, Triplett has been working in the lab of Mary-Ann Bjornsti, Ph.D., chair of the Department of Pharmacology and Toxicology in the UAB School of Medicine and associate director for translational research at theUAB Comprehensive Cancer Center. “I knew that I wanted an undergraduate research experience that would prepare me for graduate school,” said Triplett. “By working with Dr. Christine Wright in the Bjornsti lab, I have had the opportunity to perform graduate-level research and learn a wide variety of lab techniques that are specific to our lab or universal in the fields of biochemistry and molecular biology.”

Triplett and Bjornsti are “currently in the process of compiling data” on the interaction between CPT and Top1 in a yeast model system, Triplett said. “By participating in the President’s Summer Research Program, I will have the opportunity to stay on campus to finish the necessary experiments to complete this paper for submission for publication in a scientific journal.”

Triplett, who is also a member of the Chemistry Scholars Program in theDepartment of Chemistry, says the summer research will also give her an opportunity to learn new lab techniques. “My career goal is to earn a Ph.D. with a concentration in biochemistry or molecular genetics,” she said, “and to conduct biomedical research at the university level.”