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A new perspective on DNA

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Harvard Researcher Wins 3-D Genome Sequencing Method Award for a 3D image showing how DNA is tightly packed into a structure known as a "fractal globule".

"The structure is unique in that the genome is completely unraveled and despite the way it is densely packed, you can easily access the region you want to transcribe and read," explained Erez Lieberman Aiden.

It is clear that DNA sequencing has been an indispensable tool in understanding any number of biological processes. New research suggests that the way DNA is packaged in cells may be at least as important as the biological coding it contains.

A new imaging technique, developed by Erez Lieberman Aiden , a young researcher from the Society of Fellows in collaboration with Nynke van Berkum, Louise Williams, and a team of researchers from the Harvard Broad Institute and MIT and University of Massachusetts Medical School The aim of the project, which was to provide researchers with their first three-dimensional view of the human genome, was to shed new light on a number of what Aiden calls "the central mysteries of biology. "Aiden's work was recently recognized by the GE and Science Award for Young Life Scientists.

"We don't have perfect pictures yet," Aiden says, "they're blurry, but it's much better than no picture at all. »

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Producing these 3D images requires an innovative imaging technique - nicknamed Salut-C - that allows us to understand the constant evolution of nature on the genome.

"Traditional nuclear magnetic resonance images are able to determine the nature of the atoms and extrapolate the structure of the molecule from that information," Aiden said. "What we're doing is quite different. Imagine the genome of a noodle in a pot of boiling water. Every once in a while two parts of the noodle collide, and the "C-Hello" just measures how fast the two pieces of the genome collide. Not surprisingly, points that are closest to each other are more likely to collide with each other, but sometimes points further apart collide more than we expect. « 

By combining data on how often these collisions occur and how quickly the collision rate decreases at different points along the genome, Aiden and his colleagues are able to produce 3-D models that illustrate how DNA is packaged inside cells.

Aiden's hope is that the technique could eventually help unlock the physical processes that take place when genes are turned on or off, and how cells that contain identical genetic information become the many cell types that make up the human body.

"We have ideas about what happens when genes are turned on or off - we know how certain proteins show and perform certain types of operations, but it's only a small piece of a very complicated picture," he said. "The question is how genes become physically accessible to these proteins. »

Initial results suggest that when packaged in cells, DNA forms a structure called a fractal globule. Although capable of holding large amounts of material, the structure is unique in that the material is completely unraveled and that "despite the way it is densely packed, you can pull on it, easily access the area you want to transcribe, read it, and put it back in its place when you're done. « 

The data also revealed that the active and inactive parts of the genome are spatially separated, indicating that the way the genome is folded may play a role in its active genes.

"We don't know whether a gene is turned on and then immediately transferred, or whether its relocation is enough to activate a safe gene," said Aiden. "But in a sense what we've seen is a kind of epigenetics via origami. »

(Source: Peter Reuell / Harvard Gazette - March 2012)

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