Imaging gets reinvented with new DNA microscopy technique.


It is known that imaging of cells and tissues has been a cornerstone of biology ever since cells were discovered under the light microscope centuries ago, however, advances to-date in microscopy have not incorporated the growing capability to make precise measurements of genomic sequences. Traditionally, scientists have used light, x-rays, and electrons to peer inside tissues and cells, and while microscopy illuminates spatial detail, it does not capture genetic information unless it is performed in tandem with separate genetic assays. Now, a study from researchers led by Harvard University develops a new way of mapping cell populations and visualizing how biomolecules, including different sequences of DNA and RNA, are organized spatially in cells and tissues. The team state their approach, dubbed DNA microscopy, doesn’t require any optical or other specialized equipment, instead using synthetic nucleic acid barcodes to pinpoint molecules’ relative positions within a sample. The opensource study is published in the journal Cell.

Previous studies show that while microscopy illuminates spatial detail, it does not capture genetic information unless performed in tandem with separate genetic assays. Conversely, genetic-based sequencing does not capture spatial details. What hasn’t yet been developed is a single technology which can do the job of both optical and assay-based methods. The current study develops an imaging technique, dubbed DNA Microscopy, which spatially maps DNA and other biomolecules in cells and tissues.

The current study utilises tiny tags, made out of customized DNA sequences, each about 30 nucleotides long, designed to latch onto every DNA and RNA molecule in a cell. Results show the tags are replicated until there are hundreds of copies of them within the cell. Data findings show that when these copies interact with one another, they combine to make unique DNA labels.

The group state that the interactions between these DNA tags is key, and once the labeled biomolecules are collected and sequenced, a computer algorithm decodes and reconstructs the tags’ original positions within the cell, creating a color-coded virtual image of the sample. They go on to explain pinpointing the location of each molecule is similar to how cellphone towers triangulate the locations of nearby cellphones; meaning the resulting plot is based on hundreds of thousands of different dimensions, dictated by the number of molecules with which the tagged molecules can plausibly communicate.

The team surmise they have developed a new imaging technique, namely DNA microscopy, which captures both spatial and genetic information in cells simultaneously from a single specimen. For the future, the researchers state the potential applications of DNA microscopy include looking at immune system development, nervous system architecture, and mapping genetic mutations in different cells within the same tumor in relation to their interaction with other cells and with the immune system.

Source: Howard Hughes Medical Institute (HHMI) Source

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