Microscopy Breakthrough: Scientists See Virus in Great Detail

Investigators at Purdue University, using a novel technique called single-particle electron cryomicroscopy, made a 3D image of bacteriophage Epsilon15 with hitherto unprecedented resolution of 4.5Å.

"This is one of the first projects to refine the technique to the point of near atomic-level resolution," said Jiang, who also is a member of Purdue’s structural biology group. "This breaks a threshold and allows us to now see a whole new level of detail in the structure. This is the highest resolution ever achieved for a living organism of this size." [Wen Jiang is an assistant professor of biological sciences at Purdue –ed.]
Details of the structure of a virus provide valuable information for development of disease treatments, he said.
"If we understand the system – how the virus particles assemble and how they infect a host cell – it will greatly improve our ability to design a treatment," Jiang said. "Structural biologists perform the basic science and provide information to help those working on the clinical aspects."
A paper detailing the work was published in the Feb. 28 issue of Nature.
Roger Hendrix, a professor of biological sciences at the University of Pittsburgh, said what is learned about viruses can be applied to many other biological systems.
"Understanding the proteins that create the structure of a virus gives us insight into the tiny biological machines found throughout our bodies," he said. "Getting to 4.5 angstrom using this technique is a watershed of sorts because it is the first time we can actually trace the polypeptide chain – the backbone of proteins. Now we can see the tiny gears and levers that allow the proteins to move and interact as they carry out their intricate biological roles."
The imaging technique, called cryo-EM, has the added benefit of maintaining the sample being studied in a state very similar to its natural environment. Other imaging techniques used regularly, such as X-ray crystallography, require the sample be manipulated.
"This method offers a new approach for modeling the structure of proteins in other macromolecular assemblies, such as DNA, at near-native states," Jiang said. "The sample is purified in a solution that is very similar to the environment that would be found in a host cell. It is as if the virus is frozen in glass and it is alive and infectious while we examine it…"
The team obtained a three-dimensional map of the capsid, or protein shell, of the epsilon15 bacteriophage, a virus that infects bacteria and is a member of a family of viruses that are the most abundant life forms on Earth, Jiang said…
"This demonstration shows that cryo-EM is doable and is a major step in reaching the full potential of this technique," he said. "The goal is to have it reach a 3 to 4 angstrom resolution, which would allow us to clearly see the amino acids that make up a protein."

Full story: New technique takes a big step in examination of small structures…