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Salk scientists solve longstanding biological mystery of DNA organization — Researchers image 3D genome in nucleus of living human cell for the first time.
Stretched out, the DNA from all the cells in our body would reach Pluto. So how does each tiny cell pack a two-meter length of DNA into its nucleus, which is just one-thousandth of a millimeter across?
[...] In the tour de force study, described in Science on July 27, 2017, the Salk researchers identified a novel DNA dye that, when paired with advanced microscopy in a combined technology called ChromEMT, allows highly detailed visualization of chromatin structure in cells in the resting and mitotic (dividing) stages. By revealing nuclear chromatin structure in living cells, the work may help rewrite the textbook model of DNA organization and even change how we approach treatments for disease.
"One of the most intractable challenges in biology is to discover the higher-order structure of DNA in the nucleus and how is this linked to its functions in the genome," says Salk Associate Professor Clodagh O'Shea, a Howard Hughes Medical Institute Faculty Scholar and senior author of the paper. "It is of eminent importance, for this is the biologically relevant structure of DNA that determines both gene function and activity."
[...] With their 3D microscopy reconstructions, the team was able to move through a 250 nm x 1000 nm x 1000 nm volume of chromatin's twists and turns, and envision how a large molecule like RNA polymerase, which transcribes (copies) DNA, might be directed by chromatin's variable packing density, like a video game aircraft flying through a series of canyons, to a particular spot in the genome. Besides potentially upending the textbook model of DNA organization, the team's results suggest that controlling access to chromatin could be a useful approach to preventing, diagnosing and treating diseases such as cancer.
"We show that chromatin does not need to form discrete higher-order structures to fit in the nucleus," adds O'Shea. "It's the packing density that could change and limit the accessibility of chromatin, providing a local and global structural basis through which different combinations of DNA sequences, nucleosome variations and modifications could be integrated in the nucleus to exquisitely fine-tune the functional activity and accessibility of our genomes."
I'm by no means a geneticist. Nearly anyone can take a length of rope and coil it into a compact shape. Doing it in such a way that it can be readily uncoiled is quite another thing. So how does DNA get 'coiled up' without getting tied full of knots? Folding and unfolding, then, are critical and it seems that these researchers have made some key discoveries into this.
[Aside: For those who may not be aware, SoylentNews has an official Folding@Home team. Out of nearly a quarter-million teams, I'm please to report that we have broken into the ranks of the top 300 teams in the world! At the time of this writing, the official Folding@Home site reports we are ranked 287 of 226863. More information at the Folding@home main site. We are team number 230319. Come join the team as we help in the fight against Huntington's, Parkinson's, and many other diseases. --martyb]
(Score: 0) by Anonymous Coward on Wednesday August 02 2017, @09:44AM (8 children)
Whoever achieves this will cure cancer since you can do karyotyping without killing the patient. Unfortunately it is just more misinformation in this case (this is getting really tiring), these cells are all killed by the measuring process.
(Score: 0) by Anonymous Coward on Wednesday August 02 2017, @02:16PM (7 children)
Did the paper proclaim this to be a karyotyping diagnostic for humans?
Why the fuck are you putting words into their mouth, then trash talking them for it?
(Score: 0) by Anonymous Coward on Wednesday August 02 2017, @03:52PM (6 children)
The summary claims they measured something in living cells. This is not the case.
(Score: 0) by Anonymous Coward on Wednesday August 02 2017, @05:39PM (5 children)
Measuring something from live cells is different from live-cell imaging. The paper specifically says in situ.
(Score: 0) by Anonymous Coward on Wednesday August 02 2017, @05:42PM (4 children)
I looked at the paper. I saw nothing with live cells. Please point it out.
(Score: 0) by Anonymous Coward on Wednesday August 02 2017, @06:24PM (3 children)
Most of their experiments followed this: live cells, fixed (in situ), stained, then measured. The exception being supplemental figure 1: live cells, stained, fixed, then measured. They preferred the first option because DRAQ5 is big and can possibly displace DNA-binding proteins.
(Score: 0) by Anonymous Coward on Wednesday August 02 2017, @06:54PM (2 children)
By revealing nuclear chromatin structure in living cells
Yes, the fixation killed the cells. Here is what was said:
No chromatin structure was revealed in living cells. That is a false phrase, and one that got me excited for a moment. I was like "No way! We may get some actual progress on the cancer front", but no.
(Score: 0) by Anonymous Coward on Wednesday August 02 2017, @07:54PM (1 child)
I'm aware that the cells do not survive fixation. The chromatin (of live cells) is fixed, in place (in situ), then measured.
I still don't understand why you think visualizing chromatin in a living cell would be such a big deal for cancer research. Cancerous and pre-cancerous cells would be needles in a very very large haystack. I'm not sure the cost effectiveness of such a diagnostic would ever really work out. Far in the future, I'd guess such a image could be combined with a multi-lazer system (similar to two photon microscopy) to fry individual cells.
(Score: 0) by Anonymous Coward on Wednesday August 02 2017, @10:12PM
I can think of many ways to get at cancer if "in vivo karyotyping" tech was available. I honestly do not have a good idea of achieving that first step though, and really don't like interacting with the biomed community (where everyone feasts off the false hopes of laypeople), so I wait and horde them to myself.