Even at the molecular level, life doesn’t sit still. In the real world, organic biomolecules are a far cry from the static, simplified models often depicted in high-school or college biology courses. They are fast-moving, jittery structures that spin, change shape and bounce off each other.
Ongoing research at the High-Resolution Nuclear Magnetic Resonance (NMR) Spectroscopy shared resource is advancing our understanding of this kinetic process--and how this motion influences everything from gene regulation to the development of cancer.
Hashim Al-Hashimi, PhD, Duke Professor of Biochemistry, has been a heavy user of this shared resource since arriving at Duke just over a year ago. His research focuses on the properties of RNA and DNA, the molecules that make up each cell’s genetic code and that are essential for life.
“The structure and function of RNA and DNA can be difficult to study because they’re very mobile molecules,” Al-Hashimi said. “They can be difficult to crystallize to examine by x-ray crystallography, and even then, the still images don’t tell the entire story of how these molecules function.”
“The high-resolution NMR spectroscopy shared resource is uniquely suited to studying the structure and function of mobile molecules such as nucleic acids,” Al-Hashimi said. “NMR spectroscopy not only allows one to zoom into every single atom in a molecule, but also to measure its motions, or ‘jitters,’ over a broad range of timescales, from picoseconds up to hours or days.”
Such “quantum jitters” were the subject of a high-profile article recently published in Nature. Al-Hashimi and colleagues used the NMR spectroscopy shared resource to observe how tiny movements in DNA or RNA molecules lasting only 50 to 200 microseconds may contribute to mutations that drive evolution and cause cancer.
Al-Hashimi has also started using NMR spectroscopy to analyze miRNA 21, a type of short RNA molecule associated with the development of many cancers. Further study of this molecule could aid early diagnosis and improve our understanding of how cancer forms.
When it comes to the high-resolution spectroscopy shared resource’s potential for cancer research, miRNA is just the tip of the iceberg, said Leonard Spicer, PhD, Professor of Biochemistry and Radiology and the director of the shared resource.
“Researchers here are exploring some great frontiers in molecular and cell biology,” Spicer said. “For cancer research this includes everything from characterizing metabolic pathways, to mapping tumor cells, to investigating the starting elements of various cancers.”
The shared resource offers access to six high-field, high-resolution NMR spectrometers, including a state-of-the-art, ultra-high field 800 MHz spectrometer and a newly installed 700 MHz spectrometer fully configured for biological research. In September, the resource will install another $1.3 million 700 MHz instrument which will have both liquid and solid state capacity.
The shared resource’s staff, which includes Spicer, two senior scientists and one instrument specialist, also work with each researcher to make sure they get the most they can out of the instruments.
“We provide training and work side-by-side with people from the cancer center,” Spicer said. “We’re aware that our cancer research community comes from a variety of backgrounds, and we want to help each scientist as much as we can.”
Al-Hashimi agrees. “The facilities themselves are a national treasure, but it’s really the people here who make everything work. They not only make this powerful technology accessible to experts and non-experts alike, but they push the systems to their limits so that the user obtains the highest quality data.”
“I had high very high expectations coming here a year ago, and they were all exceeded,” Al-Hashimi said.