JUN 20, 2019 4:38 PM PDT

A New Kind of Microscopy is Created

WRITTEN BY: Carmen Leitch

Scientists have developed a tool for using gene expression to get an image of a cell, called DNA microscopy. The technique requires some simple methods as well as genetic sequencing and an algorithm. The genetic material in the cell is labelled, providing information about the spatial arrangement of cellular components. The researchers have used DNA microscopy to study human cancer cells, and they want to apply it to a variety of other cells in which small changes in genetic sequences have significant impacts, like immune cells.

A comparison of images of cells captured with DNA microscopy (left), and a fluorescence microscope (right). Scale bar = 100 micrometers. Credit  J. Weinstein et al./Cell 2019

"It's an entirely new category of microscopy," said Howard Hughes Medical Institute (HHMI) Investigator Aviv Regev. "It's not just a new technique, it's a way of doing things that we haven't ever considered doing before."

In DNA microscopy, short genetic sequences called unique molecular identifiers (UMIs) are tagged. A sample under analysis would be decorated with UMIs. Many of those tags will eventually collide with one another, and they will link together. Molecules that are closer together will join more frequently, and the ones that are farther apart won’t create as many connections. All of the interactions between the tags have to be genetically sequenced, and then analyzed with an algorithm, that assess about 50 million base pairs.

Ultimately, a two- or three-dimensional image is made that illustrates the position of molecules in space. A drawback is the difficulty in dealing with empty spaces, which the researchers are working to improve.

"We believe that the most exciting applications of this technology are in areas of biology in which mutations, RNA editing, and other forms of nucleotide-level variation work hand in hand within the organism to either produce physiological outcomes or cause disease," said biophysicist Joshua Weinstein.

Using DNA microscopy, scientists can identify different cells (colored dots) within a sample -- with no prior knowledge of what the sample looks like. / Credit  J. Weinstein et al./Cell 2019

In biological research, it’s critical to understand what happens on a cellular level. There are a variety of techniques for doing that, but many involve intense preparations and expensive equipment. It can also be difficult to see what many different molecules are doing at once. Now scientists can get a look at what happens in the cell on a genetic level.
 
"You're basically able to reconstruct exactly what you see under a light microscope," Weinstein noted. He added that the techniques compliment each other; sparse molecules can be seen with light microscopy and dense molecules, even in clumps, can be resolved with DNA microscopy.

"By capturing information directly from the molecules being studied, DNA microscopy opens up a new way of connecting genotype to phenotype,” said HHMI investigator and molecular biologist Feng Zhang.

Weinstein discusses the technqiue in the video.


Sources: AAAS/Eurekalert! via HHMI, Cell Press, Cell

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
AUG 01, 2021
Cell & Molecular Biology
Revealing a Major Regulator of Aging
AUG 01, 2021
Revealing a Major Regulator of Aging
Ubiquitin is a crucial, small protein that is thought to be present in all eukaryotic cells and is very similar from one ...
AUG 06, 2021
Genetics & Genomics
A Method to Efficiently Edit Bacterial Genomes Without Selection
AUG 06, 2021
A Method to Efficiently Edit Bacterial Genomes Without Selection
Gene editing has advanced in many ways over the past few decades. Most methods in genetic engineering involve altering t ...
AUG 07, 2021
Cancer
New Drug Combo Eliminates Pancreatic Cancer in Mice
AUG 07, 2021
New Drug Combo Eliminates Pancreatic Cancer in Mice
A combination of three immunotherapy drugs can eliminate pancreatic tumors in mice. The study was published in Canc ...
AUG 12, 2021
Cancer
Promising Drug Target Identified for Deadly Ovarian Cancer
AUG 12, 2021
Promising Drug Target Identified for Deadly Ovarian Cancer
Scientists at the University of Alabama at Birmingham have identified a gene called DOT1L for its role in progressing th ...
AUG 17, 2021
Neuroscience
When Do I Know I'm Me? Researchers Pinpoint Consciousness Patterns
AUG 17, 2021
When Do I Know I'm Me? Researchers Pinpoint Consciousness Patterns
Anti-correlated neurobiological shifts exist between two brain networks involved in consciousness, the "default mode net ...
AUG 31, 2021
Genetics & Genomics
A Method to Detect Genetically Modified Animals in the Environment
AUG 31, 2021
A Method to Detect Genetically Modified Animals in the Environment
Genetically modified mice, fruit flies, and zebrafish are commonly used in research. Scientists have now developed a met ...
Loading Comments...