Scientists believe that understanding how chromatin — the bundle of the DNA double helix and proteins — is arranged within a cell’s nucleus is key to understanding the root cause of cancer. However, our ability to look at DNA molecules is limited by the resolving power of currently used nanoscopy technologies, most of which can discern structures located few tens of nanometers apart.
Unfortunately, the 10-nanometer resolution threshold is not powerful enough to study individual DNA molecules, which are roughly 3 nanometers across.
A team of researchers from the Northwestern University in Illinois announced Friday the development of a new imaging technology that drastically increases this resolving power. The technique, which exploits the fact that DNA molecules fluoresce when illuminated by particular wavelengths of light, is also the first to see DNA “blink.”
Until now, it was believed that DNA and histones did not naturally give off light. However, the researchers discovered that when illuminated with visible light, the biomolecules get excited and light up well enough to be imaged without fluorescent stains.
“People have overlooked this natural effect because they didn't question conventional wisdom,” Vadim Backman, a nanoscale imaging expert at the university, who presented the findings at the American Association for the Advancement of Science’s annual meeting in Boston, said in a statement. “With our super-resolution imaging, we found that DNA and other biomolecules do fluoresce, but only for a very short time. Then they rest for a very long time, in a 'dark' state. The natural fluorescence was beautiful to see.”
This technique — the first to breach the 10-nanometer threshold — overcomes a key hurdle that current DNA-imaging technologies face. The problem with current technology used for the purpose is that it relies on special fluorescent dyes to enhance contrast of the biomolecules. This can, however, perturb cell function, and eventually kill them — both of which are undesirable effects in scientific studies.
“Our technology will allow us and the broader research community to push the boundaries of nanoscopic imaging and molecular biology even further,” Backman said. “Insights into the workings of the chromatin folding code, which regulates patterns of gene expression, will help us better understand cancer and its ability to adapt to changing environments.”