2024-03-21 19:25:00
Cells are like the subway during rush hour when the train drivers are on strike: countless molecules come, go and jostle past each other. If you want to understand what is happening exactly, you would have to record it with high-resolution cameras in order to distinguish individual actors.
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Researchers are already familiar with such a monitoring technique on the smallest scale, known as single-molecule microscopy. But even the best cameras have trouble tracking individuals from start to finish. Because in the turmoil of millions of proteins in a cell, the molecules cover and overlap one another.
Remote control with light
Using a new technique, biochemist Helge Ewers from the Free University of Berlin has now succeeded in releasing a few isolated, color-marked proteins specifically into the cell. This makes it possible to look at them in the context of their surroundings. Even in a crowded subway, the lone partygoer with the flashing hat still stands out from the crowd.
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Millions of proteins live in a simple yeast cell; in animals there can be even more.
As Ewer’s team explains in the journal “Nature Methods”, they control the process with light: they use a protein that can be split into two parts at a defined breaking point using UV radiation. At the genetic level, it can be combined with other protein sequences and a dye and then introduced into the cell to be observed.
The cell produces the individual components as a chain and then a short, high-energy laser flash is enough to cut the bonds between the links. Ewer’s team had their Eureka moment when they realized that the intensity of the radiation determined the amount of protein released.
“We knew then that our technology had a wide field of application and would help many researchers,” Ewer’s colleague Purba Kashyap was quoted as saying in a report. It also says that there are already many people interested in the technology that he developed together with laboratories in Berlin, Hamburg and Tokyo – also because it uses light as a mild agent and is therefore not invasive.
And it shouldn’t just stop at observations: Because the process allows specifically defined amounts of protein to be released, it can also control biochemical processes. Ewer’s team was able to restore the function of an enzyme and an ion channel in mutated immune cells. In principle, this would also be possible in the developing embryo or in living animals, he writes in his paper. Next, Ewers wants to test the technology on fruit flies.
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In Berlin, cell biological research with light – called “optogenetics” – has a long tradition. The optogenetics pioneer Peter Hegemann, for example, works at Humboldt University. The biophysicist succeeded in introducing light-sensitive proteins from algae into the nerve cells of fish, flies or mice and thus switching them on or off. However, the human brain is too large and opaque for most such interventions.
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