In a Biology laboratory in Mendel Science Center, tanks of iridescent zebrafish line the walls. They are not only beautiful to look at, but also model organisms for studies of vertebrate development and gene function. Villanova students working with Angela DiBenedetto, PhD, associate professor, Biology, are using these fish to examine specific genetic factors that can contribute to the risk of developing diseases like cancer.
Certain regions of chromosomes contain DNA sequences, or genes, critical to normal cellular functions, and mutations in such genes increase that risk. The gene Brd2 is a key regulator—it controls the expression of many other “target” genes involved in both cell division and cell death. It is a known protooncogene—a normal gene which, when altered by mutation, becomes an oncogene that can push cells inappropriately into mitosis or replication, contributing to cancer. It is also a factor in neural development and its deregulation may lead to juvenile myoclonic epilepsy.
In summer 2018, Villanova Biology majors Isabella (Bella) Burda '19 CLAS and Alexandra (Allie) Quatrella '19 CLAS each earned a Villanova Undergraduate Research Fellowship to study Brd2 in Dr. DiBenedetto’s lab.
Dr. DiBenedetto’s field of expertise is molecular biology and genetics, and she has long been researching the role Brd2 plays in how the fundamental processes of cell death, differentiation and division are integrated and cross-regulated, so that normal development of the vertebrate embryo is achieved. In her lab, she and her students use freshwater tropical zebrafish as a model system to determine how mutations in Brd2 may lead to developmental abnormalities and disease.
“On the surface, humans appear to be completely different than zebrafish, but we are actually far more similar to them than you might think,” Allie says.
About 70 percent of human genes are found in zebrafish, which, as vertebrates, also have two eyes, a mouth, a brain, a spinal cord and other physiological attributes in common with humans. Therefore, any type of disease that causes changes in these shared body parts in people can theoretically be modeled using zebrafish.
For Bella, a Villanova student-athlete juggling academics with the substantial time commitment that Division I competition entails, earning the VURF fellowship allowed her to work significant hours in Dr. Benedetto’s lab for the first time. She was able to make substantial progress toward her senior thesis, in which she hopes to provide new insight into the mechanisms of Brd2 action and its control of cell death in both fish and humans.
“Dr. DiBenedetto has given me so much of her time to help me become accustomed to the workings of the lab and everything I need to know to pursue my research,” says Bella. “She’s so accessible."
Allie has worked in Dr. DiBenedetto’s lab since her sophomore year, and she attended and presented at the Society for Developmental Biology Annual Meeting with her this summer. In her senior thesis she hopes to shed light on the role of Brd2 overexpression in blood cancers, including leukemia. Allie hopes to become an Army physician, while Bella is intent on pursuing a career in molecular biology/genetics research. Allie's VURF fellowship was funded by the College of Liberal Arts and Sciences’ Dean’s Fund for Strategic Initiatives.
“Students like Bella and Allie are one of the reasons why I love what I do. Watching them achieve progressively higher levels of understanding involving experimentation, and synthesis and communication of scientific ideas, is amazing,” says Dr. DiBenedetto. “As members of the lab group, they are also defending their thinking and conclusions, giving one another constructive feedback, all the while considering the impact of science and technology on society.”