Pavoni ’12 Finds a Future of Discovery Through Faculty Genome Research

By schwartzsa | September 8, 2011

Nickodemo Pavoni ’12 recently completed his second consecutive summer working under the supervision of his academic and research adviser, Dr. Sheryl T. Smith, Assistant Professor of Biology, investigating how specific DNA sequences known as insulators help to regulate the expression of genes.

Insulator sequences were first discovered in the model organism Drosophila melanogaster (the common fruit fly) and have since been found in numerous and diverse species. Recent studies have shown that insulator sequences play a role in human development and disease, although the mechanism of how these sequences function in the context of the genome is still largely unknown.

Pavoni and others in the Smith lab are using bioinformatics as a tool to make predictions about how these sequences function in 12 species of Drosophila that span 350 million years of evolution. They then use a variety of molecular biology techniques to test their hypotheses. The experience has inspired a new passion for molecular biology research and altered Pavoni’s intended path for the future.

Pavoni decided to get involved in faculty research after attending Arcadia’s annual Research Expo, where he had to opportunity to learn about the faculty research on campus. He was immediately intrigued by Smith’s research and began working on a research project shortly thereafter. He has also become more interested in the rapidly emerging field of bioinformatics, and is enrolled in a course in Bioinformatics, recently developed by Smith and Dr. Carlos Ortiz, Associate Professor of Math and Computer Science.

Fruit flies have been used as a model organism for studying cellular processes and human disease for nearly a century. For example, much of our understanding about neurodegenerative diseases such as Parkinson’s, Alzheimer’s, and Huntington’s has come from studies that use Drosophila as a model organism. As there exists high conservation between Drosophila and human insulator sequences, a better understanding of the function of these elements in the fly will shed light on how insulators specify individual differences among humans and further elucidate their role in development and disease.

“We have learned many lessons from the Human Genome Project,” explains Smith. “Less than 2 percent of the entire human genome consists of genes that are expressed (code for proteins), while the remaining percentage of the genome is represented by non-coding sequences. The non-coding regions, once naively referred to as ‘junk DNA’ are now thought to contain critical regulatory information that help specify when, and in which cell types, genes should be expressed. Although abnormal development and disease have been attributed to mutations/deletions of numerous genes, the importance of understanding the effect of alterations in non-coding DNA sequences, such as insulators, is equally as essential given the relative proportion of non-coding regulatory sequences in the genome.”

Pavoni is working with a class of insulator sequences discovered by Smith and colleagues that associate with the protein CTCF and are thought to play a direct role in the expression of genes. He is using a variety of molecular biology techniques including Western blotting to test whether the CTCF protein is found in other species of Drosophila. Gaining this information will allow further testing to find whether the CTCF protein binds to similar sequences across species. Since the CTCF protein is also found in mammalian cells, its function in Drosophila can be extrapolated to its function in higher organisms, including humans. Pavoni has already detected CTCF in three species and is continuing experiments to determine if CTCF is also found in nine other Drosophila species. He will use this research as part of his Senior Capstone project.

“It’s one thing learning about these experiments in class, but it is a total different story when you are doing the experiment with your own hands,” he says. “Having Dr. Smith there with me, guiding me each step of the way, has made me enjoy this so much more.”

When friends and family noticed his increased happiness and enthusiasm toward conducting research rather than the initial goal of attending medical school, Pavoni realized graduate school was a better choice for him.

“[The lab] feels like a second home at Arcadia. I love being there, and I spend a lot of time there. It is thanks to my mother, for always being there for me, and Dr. Smith, for teaching me and being my mentor, that I have found what I want to do with my life: conducting research in genetics and molecular biology.” He notes that another benefit to conducting research is meeting friends with similar interests. “Working together in the lab under Dr. Smith has created a bond between Amy Lloyd, Kyrillos Awad, Roma Patel and I that is so unique that it is difficult to explain. My fellow researchers are the best people I know.”

In addition to being a member of the Biology Club and Pre-Med Club, Pavoni is the current Treasurer of the American Sign Language (ASL) Club.

“One of the very best things that Arcadia offers its students is the opportunity to conduct state-of-the-art research one-on-one with our gifted faculty,” said Arcadia’s President Carl (Tobey) Oxholm III. “Here, discovery and innovation are not just read about in books – they are experienced with the hands and a mentor. These experiences prepare our students well for graduate schools and careers and help to ensure that our country will have creative minds eager to take on new challenges. But these experiences also create informed citizens, as our students know firsthand how difficult true scientific inquiry is and are better able to evaluate and participate in public discourse about scientific issues that will have local, national and global significance in the coming decades.”

Photo by Josh Blustein