Secrets of plague unlocked with stunning new imaging techniques
imaging LPS and TLR4 receptors on the membrane.
“Current light microscopy capabilities are akin to looking out the window of an airplane and seeing the irrigation circles. You know that plants are there, but you can’t tell what kinds of plants they are or what shape the leaves are,” said Carson, a Sandia immunologist who was an integral part of the project. “But with this technology, it’s like zooming in and seeing the leaves and the structure of the plants. That buys you a lot in terms of understanding what’s happening within a cell and specifically how the proteins involved interact.”
In 2009 the National Institutes of Health awarded Timlin a five-year, $300,000-a-year innovation grant. Next on the team’s agenda is developing the capability to image live cells in real time using spectral Stimulated Emission Depletion, or STED. “We’re working toward using a version of superresolution that’s much more live-cell friendly, and extending that in terms of what colors are available to do multiple colors, while maintaining the live-cell friendliness. I see this as a beginning of a long development in this type of imaging technology,” Timlin said.
Potential applications likely will expand as the technology reveals previously unattainable details of cell signaling. Eventually, the Sandia team would like to be able to visualize protein/protein interactions.
“Every biological process that goes on in your body is somehow controlled by proteins forming complexes with other proteins or complexes in the membrane, so this would give you this ability to look, with high spatial resolution and multiplexed color capabilities, at four or more things in a living cell, which can’t be done very easily right now. It can be done in pieces, but we want to see the whole biological process,” Timlin said.
The technology has exciting potential in immunology and drug discovery. Improved imaging could show the mechanisms viruses use to invade cells, which might lead to drugs that would block entry. “We’re hoping to do something like label the viral particles and watch them in real time, or as close as we can to real time, in the internalization process,” Carson said. “With the superresolution technique, we can actually watch them move through the membrane and see if there are other structures being recruited by the virus to the site of internalization.”
The release notes that Sandia originally developed the technology in support of its biological national security programs, but the team wants to expand the technology into other areas such as biofuels to better understand where and when different pigments are located on the membrane of oil-producing algae. This would provide valuable insight into their photosynthesis functions, which could lead to more efficient biofuel production.
“A lot of this work is in its early stages, but we’re encouraged by what we’re seeing and excited about its future potential,” Aaron said.
