After years of research, a team of Boston University researches recently discovered a new method for measuring-down to the nanometer-the shape of DNA molecules on a fluorescent surface. The researchers say the discovery will have immense impact on the future of molecular biology and the approach that future scientists will take on developing solutions to complex scientific problems.
The collaborative and interdisciplinary team worked almost five years to arrive at the current technology and methodology.
“The team … includes people from physics, electrical and computer engineering,” Bennett Goldberg, one of the lead researches for the project, said. “The biomedical engineering department … started working together when [Professor M. Selim] Unlu, [Professor Charles] Cantor and I started to collaborate four or five year ago.”
The concept may seem abstract, but Goldberg explained the technique in what is termed “soap bubble physics.”
Goldberg said the shape of DNA molecules had been established by other methods in the past, but this method, called “spectral self-interference fluorescence microscopy,” allows DNA molecules to be measured when they are on a fluorescent label.
“So the idea is that if you look at a soap bubble, and there’s light shining on it from behind you, you see different colors,” the Physics Department chair explained. “And the reason you get different colors is because there’s constructive and destructive interference in the reflection of the light, on the front and back surface of the soap bubble.
“So we’ve applied the same kind of thing … to a slightly more sophisticated area,” Goldberg continued. “Imagine if the surface of the soap bubble was spread with some fluorescent molecule, something that gives off light when you excite it.”
A light is shone on the fluorescent molecule and one beam reflects directly back. The other reflects off the substrate the molecule is placed on.
“So now you look at the interference of those two beams – the direct and the reflected one – and that interference will tell you the distance of that emitter above the surface,” Goldberg said. “And it tells it you at very high accuracy, for instance … say, less than a nanometer or so.”
This technique was then applied to DNA structure.
Biomedical engineering department Director Charles Cantor was also a key player on the discovery team.
Cantor described the significance of the discovery and what it means for the future of research and measurement of molecular and cellular interaction.
“There is a tremendous amount of work that is being done with DNA on surfaces … and most of those surfaces are very poorly characterized,” Cantor said, “because we didn’t have tools that allowed us to characterize them. Now, at least in principal, we can learn a lot about what the molecules look like on these surfaces and how they’re behaving.”
Cantor said this technology should be implemented on a large scale.
“The same tool is potentially applicable to lots of other problems,” he said. “If we want to understand the structure of biological objects very close to surfaces, and there’s a lot really to be done.”
Until now, Cantor explained, it was very difficult to discover how the bottom of a cell would interact with the surface it was on.
“So it’s a very new technique,” he said, “but I think it has a considerable power, potentially.”
Goldberg said the new measurement system could further the development of BioArray technology that helps analyze DNA sequences for diseases, including cystic fibrosis.
“We hope that this will be sort of a watershed in the area of BioArray technologies,” Goldberg said. “We’re not sure, no one ever knows, but we think that it will have a big impact in the ability of these technologies to move from the research to perhaps clinical practice.”