Tammy Dwyer’s extraordinary research maps synthetic DNA
Six scientists, including James Watson and Francis Crick, discovered the now-famous double helix structure of DNA; that marvelous messenger molecule containing life’s genetic instruction manual, written with only four letters representing four types of molecules — the nucleobases known as A, C, G and T.
In the years since — a fantastic era of genome mapping, forensic breakthroughs and medical miracles — researchers have worked to expand DNA’s genetic alphabet by inventing synthetic nucleobases. Their goal: to develop new organisms with potentially useful new properties and functions. Designer life, if you will.
This futuristic scenario is now unfolding with the help of a San Diego-based research group that includes USD Professor of Chemistry and Department Chair Tammy Dwyer.
Scripps Research Institute researcher Floyd Romesberg led the team, which designed and created two synthetic nucleobases, called 5SICS and NaM, a compatible pair that apparently feels right at home within the DNA molecule.
The most stable and efficient synthetic base pair yet discovered, 5SICS and NaM easily take on the work of A, C, G and T, and even the critical task of DNA replication.
Using her expertise in nuclear magnetic resonance spectrometry, Dwyer mapped the 3D solution structure — allowing Romesberg to infer behavior — of the altered DNA molecule during this delicate process of copying and passing on the genetic information.
She found that unlike A, C, G and T, the synthetic bases 5SICS and NaM overlap slightly within the DNA molecule rather than meet edge to edge. But during replication, they line up their edges just long enough for the normal sequence of cell division to proceed uninterrupted.
“This is one of the first times the precise steps of DNA replication have been presented with this level of structural detail,” Dwyer explains. “The opportunity to make even a small contribution to such an exciting project is thrilling. I’m very proud of this work.”