A research team led by Israelis claims to have created an unprecedented “molecular Google Map” of a brain memory center, in a first application of technology that can help in the fight against Alzheimer’s and other diseases.
The discovery allows researchers to amplify RNA (ribonucleic acid) in nanoscale resolution without having to destroy the tissue to remove the RNA for analysis, giving a view of brain tissue that until then was out of doctors’ reach.
The ability to sequence RNA, a building block of life that uses DNA information to create proteins, has transformed biology and medicine. But in trying to analyze the RNA from the brain tissue that had been destroyed, doctors only got a much less detailed view – like a list of cities instead of a map – creating a major barrier to researching diseases that affect brain function.
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On Thursday night, a team from Bar Ilan University, Harvard and MIT published a peer-reviewed survey in the journal Science detailing how they managed to analyze and map a brain’s hippocampus, its main memory center, without destroying tissue.
The brain tissue they used came from a mouse, but they also tried their method on various human tissues. The researchers say their technology may have benefits in the treatment of brain diseases, such as Alzheimer’s, and others, including cancer.
Images generated with the new technology that allows multiplexed mapping of RNAs in nanoscale resolution in all intact tissues. (Shahar Alon, Daniel Goodwin, Ed Boyden)
“It is the equivalent of having a vast and detailed Google map with the location of the genes within 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 main author of the study.
“This new method allows us to visualize and measure millions of RNA molecules within tissue with nanoscale precision, without having to extract them as we previously did,” he told The Times of Israel. “We can zoom in, just like you can on Google Maps, and see the molecules up close.”
To develop the new method, Alon modified a widely available gel made of acrylamide, “the same substance used in diapers to absorb urine,” and used it to swell the tissue to about four times its size. He then customized the existing microscopes to give a detailed picture of the RNA.
Analyzing RNA in situ means that doctors not only receive information about the molecules’ identities, but also where exactly they are located within the tissue, which can be valuable in advancing understanding of diseases, said Alon.
Illustrative: A scientist at the NY Genome Center in New York demonstrates the equipment used in single cell RNA analysis on Wednesday, September 26, 2018. (AP Photo / Ritter)
That potential is clearest in the brain, where the location of molecules is known to be crucial for proper functioning, especially for processes like learning and memory, said Alon.
“We believe that this can give a new idea of how Alzheimer’s affects the location of genes in the brain, and it can help in the development of new treatments,” he said.
Dr. Shahar Alon of Bar Ilan University (courtesy of Bar Ilan University)
The RNA can be used as a “marker” or tool to obtain a broad picture of cellular behavior in a tissue, which means that the new research has the potential to analyze cancer cells, said Alon. This is because the technology can be used to show how a given patient’s cancer cells are being affected by immune cells.
“One of the great mysteries of immunotherapy is why it works well in some patients and not in others. The maps we are building could reveal the difference, in biological mechanisms, between patients who are reacting and those who are not.
“Imagine if you could do a biopsy of a patient and know in advance, with some certainty, whether immunotherapy will help that person or not. This can be useful for doctors’ decision-making and the development of new immunotherapy drugs that help patients who are not responding to current drugs, ”he said.
