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Israel-led team creates a ‘Google Map’ of brain RNA; may help Alzheimer’s fight

An Israeli-led research team says it has created an unprecedented “molecular Google Map” of a brain’s memory center, in a first application of technology that may help in the fight against Alzheimer’s and other diseases.

The breakthrough allows researchers to zoom in on RNA (ribonucleic acid) at nanoscale resolution without having to destroy the tissue to remove the RNA for analysis, giving a view of brain tissue that was hitherto out of doctors’ reach.

The ability to sequence RNA, a building block of life that uses the information from DNA to create proteins, has transformed biology and medicine. But when trying to analyze RNA from brain tissue that had been destroyed, doctors could only get a much less detailed view — like a list of cities instead of a map — creating a major barrier to research into diseases that affect brain function.

On Thursday night, a team from Bar Ilan University, Harvard and MIT published peer-reviewed research in the journal Science detailing how they managed to analyze and map out the hippocampus of a brain, its main memory center, without destroying the tissue.

The brain tissue they used came from a mouse, but they have also proved their method on various human tissues. The researchers say their technology could have benefits in treating diseases of the brain like Alzheimer’s, and others including cancer.

Images generated using new technology that enables multiplexed mapping of RNAs at nanoscale resolution throughout intact tissues. (Shahar Alon, Daniel Goodwin, Ed Boyden)

“It’s the equivalent of having a vast and detailed Google Map of the location of genes inside the brain, and other tissues, rather than a low-resolution image or a simple list of the 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 within the tissue with nanoscale precision, without having to extract them as we did previously,” he told The Times of Israel. “We can zoom in, just like you can on Google Maps, and see the molecules very close up.”

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 tissue to around four times its size. He then customized existing microscopes to give a detailed picture of the RNA.

Analyzing RNA in situ means that doctors don’t only receive information on the identity of molecules, but also where exactly they are located inside tissue, which can prove valuable in advancing the understanding of diseases, Alon said.

This potential is clearest in the brain, where the location of molecules is known to be crucial for proper functioning, especially for processes such as learning and memory, Alon stated.

“We believe this could give a new glimpse into how Alzheimer’s affects the location of genes in the brain, and this could help in developing new treatments,” he said.

RNA can be used as a “marker” or tool for getting a broad picture of cell behavior in a tissue, which means the new research has potential for analyzing cancerous cells, Alon said. This is because the technology can be used to show how cancer cells in a particular patient are being impacted by immune system cells.

“One of the big mysteries of immunotherapy is why it works well in some patients and why it doesn’t in others. The maps we are building could reveal the difference, in biological mechanisms, between patients who are reacting and those who aren’t.

“Imagine if you could take a biopsy of a patient and know in advance, with some certainty, whether immunotherapy is going to help this person or not. This could be helpful for doctors’ decision making, and in the development of new immunotherapy drugs which help patients who are not responding to current drugs,” he said.

Source: Nathan Jeffay – TOI