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How can we trace single diseased cells in the intact brain or human heart? Matthias Mann’s team at the Institute developed a new technique called DISCO-MS that solves this problem. DISCO-MS uses robotics technology to obtain proteomics data from “disease” cells that are precisely identified early in the disease, his LMU wrote in a press release.
Most diseases are asymptomatic at first. Affected people are usually still fine – symptoms have not yet appeared or are too mild to notice. A virus may have started replicating, or a malicious cell may have split more often than it should.
The development of DISCO-MS has made this task easier. DISCO-MS is a combination of mouse and human tissue clearing methods. Determine molecular configurations using the latest robotics and proteomics techniques.
Transparency to detect early molecular changes
DISCO-MS begins with so-called DISCO tissue clearing, which clears the mouse body and human organs. This allows fluorescently labeled cells to be easily identified in intact tissue at specific sites using high-resolution three-dimensional microscopy.
Once the regions of interest are identified, they are isolated using a new robotic technology called DISCO-bot. It was developed by his PhD mechanical engineer Furkan Öztürk. A student in Ertürk’s laboratory. The robotically extracted tissue is then processed for proteomic analysis using advanced mass spectrometry (MS) methods developed by former Ph.D. He Andreas-David Brunner. A student in Mann’s lab. This high-tech approach allows full molecular characterization of any tissue region identified in her 3D in whole mice or human organs.
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To showcase the power of this method, first author Harsharan Singh Bhatia and colleagues applied DISCO-MS to an Alzheimer’s disease (AD) mouse model and human cardiac atherosclerotic plaques (pathological hardening and narrowing of blood vessels). ). The team also applied artificial intelligence (AI) to identify typical AD plaques in the early stages of the disease. Subsequent proteomic analysis of plaques has provided an unbiased, large-scale study of proteins affected by AD. The analysis also revealed new molecular players that could be biomarkers for Alzheimer’s disease.
In the human heart, researchers were interested in the composition of tissue around atherosclerotic plaques. AI detection and robotic extraction of tissue has again enabled the identification of molecular pathways of dysregulation in human cardiac cells associated with aortic plaque. These results are important findings as they form the basis of potential therapeutic targets.
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