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An Israel-led research team claims to have created an unprecedented “molecular Google map” of a brain’s memory center, as part of a first application of technology that could help fight AIDS. Alzheimer’s and other diseases.
This breakthrough allows researchers to zoom in on RNA (ribonucleic acid) at nanoscale resolution without having to destroy tissue to remove RNA for analysis, giving a view of brain tissue hitherto beyond the reach of doctors.
The ability to sequence RNA, a building block of life that uses information from DNA to create proteins, has transformed biology and medicine. But by trying to analyze RNA from destroyed brain tissue, doctors could only get a much less detailed view – like a list of cities instead of a map – creating a major obstacle to researching them. diseases that affect the functioning of the brain.
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On Thursday evening, a team from Bar Ilan University, Harvard and MIT published peer-reviewed research in the journal Science detailing how they successfully analyzed and map a brain’s hippocampus, its main center. from memory, without destroying the tissue.
The brain tissue they used was from a mouse, but they also proved their method on various human tissues. The researchers say their technology could have benefits in treating brain diseases like Alzheimer’s disease and others, including cancer.
Images generated using a new technology that enables multiplexed mapping of RNAs at nanometric resolution in intact tissue. (Shahar Alon, Daniel Goodwin, Ed Boyden)
“It’s the equivalent of having a large and detailed Google map of the location of genes inside the brain and other tissues, rather than a low-resolution image or just a list of genes that are there, ”said Dr. Shahar Alon, the study’s lead author.
“This new method allows us to visualize and measure millions of RNA molecules in tissue with nanometric precision, without having to extract them like we have done before,” he told The Times of Israel. . “We can zoom in, like you can on Google Maps, and see the molecules up close.”
To develop the new method, Alon modified a widely available gel made from acrylamide, “the same substance that is used in diapers to absorb urine,” and used it to swell tissues up to about four. times its size. He then customized existing microscopes to give a detailed picture of the RNA.
Analyzing RNA in situ means that physicians not only receive information about the identity of molecules, but also where exactly they are found in the tissues, which can prove invaluable in advancing the understanding of the molecules. diseases, Alon said.
Illustration: A scientist at the NY Genome Center in New York City demonstrates the equipment used in single-celled RNA analysis on Wednesday, September 26, 2018 (AP Photo / Ritter)
This potential is most evident in the brain, where the location of molecules is known to be crucial for proper function, particularly for processes such as learning and memory, Alon said.
“We think this could provide new insight into how Alzheimer’s disease affects gene location in the brain, and it could help develop new treatments,” he said.
Dr Shahar Alon from Bar Ilan University (courtesy Bar Ilan University)
RNA can be used as a “marker” or a tool to gain an overview of cellular behavior in tissue, which means the new research has potential to analyze cancer cells, Alon said. Indeed, the technology can be used to show how cancer cells in a particular patient are affected by cells of the immune system.
“One of the big mysteries of immunotherapy is why it works well in some patients and why it doesn’t work in others. The maps we are building could reveal the difference in biological mechanisms between patients who react and those who don’t.
“Imagine if you could take a biopsy from a patient and know ahead of time with some certainty whether immunotherapy will help that person or not. This could be useful for physician decision making and for the development of new immunotherapy drugs that help patients who do not respond to current drugs, ”he said.
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