- The method can analyze the proteins in 27 cells at the same time compared to previous limitation of 3 cells, which makes it possible to map the entire brain proteom within a few years.
- The technology can identify early warning signals for Alzheimer’s before symptoms occur, when treatments have a better chance of working.
- If the team manages to scale up their methods by another 100 times, it may be possible to map the proteome for each cell in the human brain within a few years.
Protein analysis becomes more effective
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Researchers at Parallel Squared Technology Institute have developed methods that can analyze the proteins in significantly more cells at the same time than before. They work on making protein analysis as simple and inexpensive as DNA sequencing, writes Asimov Press.
Human cells contain more than 20,000 different proteins, all of which can change depending on the needs of the cell. These changes are crucial to understanding diseases such as Alzheimer’s, where protein modifications play a central role.
The cost of analyzing a cell proteom has dropped from thousands of dollars to between two and $ 50 per cell. The problem is that researchers can only analyze around a dozen cells at a time with existing technology.
Barcodes multiply capacity
The team has developed a system with nine different barcodes that attaches to the proteins. Previously, researchers could only use three barcodes at the same time. The chemistry team has created 10,000 different barcodes during the year and uses algorithms to design better versions.
The researchers have also developed a method called Timeplex. Instead of waiting 30-60 minutes between each analysis, they enter three rounds of samples every few minutes. This creates a continuous current of signals that triple capacity.
The combination of nine barcodes and three time -shifted charges allows the team to analyze 27 different proteoms in a single experiment. This is nine times more than the previous standard.
Alzheimer’s research as a test area
The institute uses its technology to study Alzheimer’s disease, which affects 7.1 million Americans. The disease is linked to at least two proteins: amyloid-β-plaque outside neurons and phosphorylated tau proteins inside neurons.
The researchers analyze neurons from Alzheimer’s patients who died at various stages of the disease, from Braak 0 to Braak 6. They cut out thin sections of brain tissue and sort them into individual neurons. Each neuron is placed in small water drops and is marked with barcodes before analysis.
The goal is to find warning signals long before plaque or tangle becomes visible. The team hopes to identify markers that appear in the early, symptomless phase of the disease when treatments have a better chance of working.
Existing drugs such as Lecanemab and Donanemab can reduce the plaque load and slow down cognitive deterioration by 27 and 35 percent, respectively. But they can only be given after the patient shows clear symptoms.
From dozen to thousands of cells
PTI was founded in 2023 by Nikolai Slavov together with Harrison Specht and Aleksandra Petelski. The team now consists of 22 people in biochemistry, calculation biology and organic chemistry.
Their current restriction is that the robot preparing cell samples can keep up with the mass spectrometers. When their barcodes and timeplex methods expand, the mechanical part of the experiment will become the bottleneck instead of the mass spectrometry.
If the team manages to scale up their methods by another 100 times, it may be possible to map the proteome for each cell in the human brain within a few years. This would have a major impact on the understanding of complex diseases.
The technology can also be used to track how the signal circuits work incorrectly in cancer, follow immune cells when they learn to recognize pathogens, or detect early changes in brain diseases long before the symptoms begin.
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