Two members of the Department of Chemistry at Franklin & Marshall College have embarked on a three-year investigation of the structure and dynamics of nucleic acids with the financial support of a grant from the National Institutes of Health.
Scott Brewer, assistant professor of chemistry, and Ed Fenlon, associate professor of chemistry, received a $195,895 grant for their project, "Development and Application of Multi-Spectroscopic, Site-Specific (MS3) Probes of Nucleic Acid Structure." The project began June 1 and will continue through May 2013. The grant will support three undergraduate researchers to assist with the project during the summers of 2011 and 2012; two Hackman scholars are working with the professors this summer.
"We want to study both the structure and dynamics of RNA hairpins," Brewer says. The professors will examine DNA and RNA at the molecular level to better understand the diverse and complicated functions of these biomolecules. They aim to develop and apply probes that will provide information about the primary environments in nucleic acids: the major groove, minor groove and sugar/backbone region.
To study the biological structure of nucleic acids, the professors will use small, noninvasive probes. The probes, they explain, are essentially substitutions that replace an atom from the native molecule. Nitrile and azide groups are particularly good candidates for atomic substitution because they are small enough to avoid disrupting the structure of the molecules.
Brewer and Fenlon will use infrared (IR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy—two powerful and complementary techniques—to perform their study. These spectroscopic techniques, coupled with the nitrile and azide probes, should allow insight into the complex structure of RNA hairpins. "Using these two techniques is one advantage of our work, because there are pros and cons with both," Fenlon says.
Brewer, a physical chemist, and Fenlon, an organic chemist, bring different perspectives to the project. They have already learned from each other in this multidisciplinary approach, something they say has become more common in their field.
The professors hope their research will validate theoretical treatments regarding RNA therapies. RNA interference therapies are in the final stage of clinical trials for eye disease (age-related macular degeneration) and in earlier stages for viral infections.
"We want to relate this to medicine," Fenlon says. "DNA can exist in more than one form. What's the clinical relevance of that? Some of this is known, and some is not known. We're developing tools to help measure this and better understand the structure of nucleic acids."