- The method can analyze proteins in 27 cells simultaneously compared to the previous limitation of 3 cells, making it possible to map the entire brain’s proteome within a few years.
- The technology can identify early warning signals for Alzheimer’s before symptoms appear, when treatments have a better chance of working.
- If the team succeeds in scaling up their methods by another 100 times, it may be possible to map the proteome of every cell in the human brain within a few years.
Protein analysis becomes more efficient
Researchers at Parallel Squared Technology Institute have developed methods that can analyze proteins in significantly more cells simultaneously than before. They work to make protein analysis as simple and affordable as DNA sequencing, writes Asimov Press.
Human cells contain more than 20,000 different proteins, all of which can change depending on the cell’s needs. These changes are crucial for understanding diseases like Alzheimer’s, where protein modifications play a central role.
The cost of analyzing a cell’s proteome has dropped from thousands of dollars to between 2 and 50 dollars per cell. The problem is that researchers can only analyze about a dozen cells at a time with existing technology.
Barcodes multiply capacity
The team has developed a system with nine different barcodes that attach to proteins. Previously, researchers could only use three barcodes simultaneously. 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 feed in three rounds of samples with a few minutes’ interval. This creates a continuous stream of signals that triples the capacity.
The combination of nine barcodes and three time-shifted loads allows the team to analyze 27 different proteomes in a single experiment. This is nine times more than the previous standard.
Alzheimer’s research as 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 plaques outside neurons and phosphorylated Tau proteins inside neurons.
The researchers analyze neurons from Alzheimer’s patients who died at different 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 droplets and marked with barcodes before analysis.
The goal is to find warning signals long before plaques or tangles become visible. The team hopes to identify markers that appear in the disease’s early, symptomless phase when treatments have a better chance of working.
Existing drugs like lecanemab and donanemab can reduce plaque burden and slow cognitive decline by 27 percent and 35 percent respectively over 18 months. But they can only be given after the patient shows clear symptoms.
From dozens 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, computational biology, and organic chemistry.
Their current limitation is that the robot preparing cell samples can keep pace with the mass spectrometers. When their barcodes and timePlex methods expand, the mechanical part of the experiment will become the bottleneck instead of mass spectrometry.
If the team succeeds in scaling up their methods by another 100 times, it may be possible to map the proteome of every cell in the human brain within a few years. This would have a major impact on understanding complex diseases.
The technology can also be used to track how signaling circuits malfunction in cancer, follow immune cells as they learn to recognize pathogens, or detect early changes in brain disorders long before symptoms begin.
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