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This diagram shows the human protein and amino acid codes in the background. The new FRET X technology can identify proteins using protein fingerprints. Chirlmin Joo Lab obtains these unique fingerprints by finding parts of the full-length amino acid code (C and K highlighted in blue letters).Credit: Delft University of Technology
in research published in natural nanotechnology, scientists from Delft University of Technology have presented a new technique for identifying proteins. Proteins carry out essential functions within our cells and also play important roles in diseases such as cancer and COVID-19. Researchers identify proteins by reading fingerprints and comparing them to patterns in a database.
Using this new technology, researchers can individually identify complete, full-length proteins while preserving all the information. This will help elucidate the mechanisms behind various diseases and enable early diagnosis.
Unfinished IKEA project
“The study of proteins in cells has been a hot topic for decades, and great progress has been made, giving researchers a better idea of what types of proteins there are and what functions they perform. ” said Mike Filius at the outset. Author of the paper.
Currently, scientists use a method called mass spectrometry to identify proteins. The most common mass spectrometry approach is the “bottom-up” approach, where full-length proteins are cut into smaller pieces called peptides, which are then measured in a mass spectrometer. Based on the data from these small pieces, a computer reconstructs the protein.
Filius said: “This is a bit like a typical IKEA project, where you’re always left with spare parts that you don’t quite know how to install. But in the case of proteins, these spare parts could actually contain many, many things.” It provides valuable information, for example, whether such proteins have harmful structures that cause disease. ”
protein fingerprint
“In order to identify a protein, you don’t need to know all the amino acids that the protein is made of. Instead, you try to get enough information so that you can use the database as a reference to identify the protein. “It’s about how we identify a suspect from fingerprints,” Filius explained.
“In previous work, we showed that every protein has a unique fingerprint, just like its human analogue. To generate a unique fingerprint from a protein, we need to “We realized that it is enough to know the position of some of the amino acids in the protein, which allows us to identify the protein,” added Dr. Raman van Wee. Candidates involved in research.
finding protein in a haystack
“These amino acids can be detected through molecules that glow under the microscope, and are attached to small pieces of DNA that bind very specifically to certain amino acids,” Van Wie explains. In this way, the team can quickly determine the position of amino acids with great precision.
“The sensitivity of this new technology, called FRET ,” Filius said. Say. This is important because it allows us to measure patient samples in case of illness.
“Our paper shows that we can detect small amounts of proteins that are characteristic of Parkinson’s disease and COVID-19,” Filius said.
“While other approaches have been investigated to identify proteins, our approach focuses on identifying complete individual proteins from within complex mixtures.” ,” Van Wie added.
For early diagnosis of diseases
Although promising, this research still requires significant development, and Chirlmin Joo Lab is looking forward to tackling it. The research group spoke with several stakeholders in clinical laboratories and the biopharmaceutical industry and found that they were very excited about the breakthrough potential of this technology.
They are also working on launching a startup to develop FRET X into a highly sensitive protein detection platform. This platform can diagnose diseases at an early stage and improve the effectiveness of potential treatments.
“This breakthrough technology deciphers the protein code and opens up exciting possibilities for early disease detection,” said Chirming Zhu, the project’s supervisor.
For more information:
Mike Filius et al, Fingerprinting of full-length single molecule proteins, natural nanotechnology (2024). DOI: 10.1038/s41565-023-01598-7