This year, Heinz-Given Professor of Biology & Pre-Medical Science and Chair of the Biology Department Grace Spatafora found herself with a rather large lab. Along with a dedicated team of students, some of which worked in Spatafora's lab over this past summer, Spatafora is working toward the lab's main objective: examining a certain protein, SloR, and its role in mediating gene expression in bacteria.
"Our lab's overarching goal is to gain an understanding of how microorganisms can adversely affect human health," said Chris Matteri '13, a member of the Spatafora lab. "In particular, we study the bacterium Streptococcus mutans, one of the main species that causes tooth decay. We hope that the insight we gain on how this bacterium causes disease at the molecular level could ultimately be used to design treatments."
Matteri noted that while the Spatafora lab's research might seem esoteric at first glance, it has implications for improving the lives and health of people across the world.
"Tooth decay may not seem very important in light of other more deadly diseases, but it has a substantial financial cost and disproportionately affects those in lower income families," said Matteri. "Poor oral health is often associated with poor general health. Additionally, Strep. mutans can sometimes cause more serious infections, such as those of the blood or the heart."
The virulence of Strep. mutans, like many other disease-causing bacterium, is modulated by genes. The "expression," or activation of these gene sequences in the bacterium, leads to increased virulence of the disease.
To assess how Strep. mutans genes are expressed, the lab is focusing on the protein SloR, which acts as a "genetic switch" turning these disease-causing genes on and off in the bacterium. What triggers SloR is the amount of metal in the environment, such as in the human mouth. An understanding of how the switch works could allow researchers to control it and keep the "bad genes" switched off permanently in Strep. mutans.
Each student in the lab has a specific objective to accomplish. Matteri's main objective is to figure out which genes the protein switches on and off. Matteri uses a process that he calls "molecular fishing."
"First I glue the protein to the DNA of the genes it is controlling, then I pop open the cells, pull the protein and its attached DNA out and see what I've found," said Matteri. "Discovering which genes the switch controls will help us figure out how the switch works."
This research opens the door to further studies that can focus on designing therapeutic treatments. These treatments could target SloR-modulated virulent genes, alleviating the process by which Strep. mutans becomes a lethal threat.
Garron Sanchez '13 began working in the Spatafora lab this past summer.
"My specific project concerns [SloR]," said Sanchez. "This protein has been shown to regulate many of the genes that cause cavity formation."
In addition to his summer work, Sanchez's project will continue into the fall semester.
"Building on my work over the summer, I am investigating the three-dimensional structure of the SloR protein in order to elucidate how this protein interacts with double stranded DNA to turn off or turn on the genes that lead to destruction of the tooth enamel," Sanchez said.
In addition to the lab's general goal of discovering what genes the protein switch controls, Matteri is working on another related project that started last year.
"That project involves using cutting-edge DNA sequencing technology to take a snapshot of all of the genes that are currently active," said Matteri. "We can compare data from different conditions to further understand which genes are controlled by our switch. Once we figure this switch out, which may be pretty soon, there will certainly be more questions to ask about the molecular biology of our bacterium."
Spatafora emphasized the shared value of hosting undergraduates in her research, both for herself and her students.
"The relationship I share with these students is mutually beneficial," wrote Spatafora in an email. "The students commit to a senior capstone experience that allows them to explore significant biological questions at the laboratory bench, prepares them for post-graduate study, provides them an opportunity to communicate their research findings to the college community and/or perhaps at a professional meeting, and affords them an opportunity to contribute to the published literature.
"I benefit from the students' hard work, which moves the research along in a way that continues to earn major funding from the National Institutes of Health, and by being able to showcase undergraduate research at national and international meetings," she continued. "I also get to watch these students evolve as independent researchers and problem solvers, some of whom go on to pursue research careers of their own. What could be more gratifying?"
Matteri also commented on the inevitable ups and downs to working in a research lab.
"Working in molecular biology can be frustrating at times," Matteri said. "Experiments take a long time. Like all science, things often don't go according to plan. But if you step back and think about it, we are programming life. The molecules we work with shape all life, including us. That's pretty cool."
Sanchez noted that the future goals for the lab are to further develop the knowledge base for microbial genetic research in the oral cavity with Strep. mutans at the forefront of this research, given its significance in dental caries development.
Other members of Spatafora's lab include Meghan Stang '13, Clark Hatheway '13 and Karl Benz '13, who were not available for comment.
Science Spotlight: Spatafora Lab
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