Researchers from the Wyss Institute of Biologically Inspired Engineering at Harvard University developed an inexpensive and easy-to-use new microscopy that simultaneously generates snapshots of many biomolecules at once in a single human cell. Last year, the team was awarded a $3.5 million grant from the National Institutes of Health (NIH) as part of an initiative to fund “high-risk, high-reward” research. In a press release from the Wyss Institute, cellular “job sites” were compared to busy construction sites with tiny cellular workers coming and going. Current methods can only spot three or four types of tiny “workers” simultaneously, at most.
“If you can only see a few things at a time, you are missing the big picture,” said Peng Yin, a Core Faculty member at the Wyss Institute and Assistant Professor of Systems Biology at Harvard Medical School. Yin’s team sought to overcome the basic laws of physics that hindered microscopists for years. The problem: when two objects are closer than approximately 200 nanometers apart – about one five-hundredth the width of a human hair – they can’t be distinguished using a traditional light microscope.
Ralf Jungmann, Ph.D., now a Postdoctoral Fellow working with Yin at the Wyss Institute and Harvard Medical School, helped develop a super-resolution method called DNA-PAINT while still a graduate student. DNA-PAINT can create ultrasharp snapshots of up to three cellular workers at once by labeling them with different colored dyes.
Yin’s team includes Jungmann, Maier Avendano, M.S., a graduate student at Harvard Medical School, and Johannes Woehrstein, a postgraduate research fellow at the Wyss Institute. Together they modified DNA-PAINT to create a new method called Exchange-PAINT and were then able to use Exchange-PAINT to capture clear images of the 10 different types of miniscule DNA origami-like structures in one image. Yin expects that with further development the method will be able to visualize dozens of cellular components at once.
“Pen’s exciting new imaging gives biologists an important new tool to understand how multiple cellular components work together in complex pathways,” said Wyss Institute Founding Director Don Ingber, M.D., Ph.D. “I expect insights from those experiments to lead to new ways to diagnose and monitor disease.”
A recent paper in Nature Methods describes the new microscopy technique.