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Yales cellular spray paint highlights dark matter of the genome

Date: 1.8.2022 

While science continues to identify and unravel the role of the thousands of proteins in the human body, many of them are too small to be picked up with current techniques. These ghost microproteins live in what scientists refer to as the "dark matter" of our genome and may play important roles in the progression of disease.

Kredit: PiccoloNamek / Wikimedia Commons.A team at Yale University has now claimed a breakthrough with a technology they liken to "spray paint" for cells, which they've now demonstrated by mapping previously unknown proteins for the first time.

Despite these advances, there remains many more microproteins to discover. Based on preliminary research, scientists like Slavoff suspect these may be connected to human disease, helping melanoma and other types of cancers evade current treatments, for example.

One of the more promising techniques for discovering microproteins today is called proximity biotinylation, which is based on the premise that by fixing enzymes to certain proteins, other proteins they interact with can be revealed by affixing a chemical tag for easy identification. There are a few variations of this technology, and Yale scientists including Slavoff have been working with a form they call MicroID.

“Our technique is like spray painting various areas of a cell with a tag that allowed us to ‘grab’ and identify all of the microproteins in that cellular region,” said Slavoff.

The researchers have now used this technique to map previously unannotated microproteins in live cells for the first time. This, the researchers write, validates the MicroID technique for use in live cells and establishes it "for discovery of microproteins and alt-proteins in vivo."

Image source: PiccoloNamek / Wikimedia Commons.





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