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The ABCs of New DNA: USD Professor Helps Expand Genetic Code

Monday, July 30, 2012

The English alphabet has 26 letters, but until recently the genetic alphabet had four — adenine (A), guanine (G), cytosine (C) and thymine (T).

However, Tammy Dwyer, USD professor of chemistry and biochemistry, recently participated in research discovering that an expanded “DNA alphabet” could carry more genetic information than natural DNA, potentially enabling novel applications ranging from more precise molecular probes to nanomachines.

Dwyer contributed to The Scripps Research Institute’s study which was reported in the June 3 issue of the scientific journal Nature Chemical Biology.

“DNA is the chemical code (or alphabet) used by the body to store genetic information such as gender, hair color, and eye color,” Dwyer explained. A particular piece of DNA or strand has many nucleobases twisted together like a necklace with A always pairing with T and G with C. A typical “gene” or piece of DNA contains approximately 3,000 nucleobases strung together, she added.

But the team of researchers, led by Floyd Romesberg, associate professor at the Scripps Research Institute, created two new nucleobases called 5SICS and NaM that can be incorporated into DNA and replicated using the natural molecular machinery in cells nearly as well as natural nucleobases.

“Other scientists have created non-natural nucleobases before, often aimed at replacing one member of a pair in a duplex – such as placing an artificial analog of T across from an A in a duplex – but there are very few non-natural pairs that are known and none have been able to be replicated as well as 55ICS and NaM,” noted Dwyer, who contributed her expertise in using NMR (nuclear magnetic resonance) spectrometry to determine the three-dimensional structure of the non-natural pair and how it fits together within natural DNA.

This work builds upon Dwyer and Romesberg’s work published in the Chemistry –  A European Journal in the fall of 2010. Two of Dwyer’s research students at USD, Danielle Pfaff ’08 and Shannon Ippoliti ’11,  analyzed the NMR data and performed the computational work that generated the 3-D structure of a similar non-natural base pair.

Now that the entire project is complete, Dwyer said the possibilities from the research are exciting. “The ability to add new ‘letters’ to the genetic code and successfully incorporate them into DNA without needing specialized machinery to do so means we could potentially develop new diagnostic tools for medicine. Such discoveries could potentially lead to completely new organisms that perform new processes or produce interesting new materials of biological relevance.”

“The opportunity to be part of cutting-edge research and make even a small contribution to an exciting project is thrilling,” said Dwyer, who spent several weeks burying her head in data spread out all over her kitchen table and on a trip to Seattle during a power outage pouring over the data by candlelight to complete her part of the story. “I’m very proud of the work.”

Along with her cutting-edge research, Dwyer was also awarded the Iota Sigma Pi Annual Centennial Award for Excellence in Undergraduate Teaching this summer. The prestigious award from the national honor society of women in chemistry is given for excellence in teaching chemistry, biochemistry or a chemistry-related field at an undergraduate institution that does not offer a graduate program in that field.

– Liz Harman

Photos by Nick Abadilla

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