I am Maureen Cavanaugh . The top story on midday edition, the famous double helix model of the structure of DNA is the one most of us are familiar with. Researchers have progressed far beyond that clunky representation in the efforts to figure out what is happening inside the human genome. A major step forward has been announced at Salk Institute. The breakthrough will help scientists see exactly how the genome is organized inside a living cell. Joining me is the associate professor for biological studies and the research our lab is the subject of the lead article in the latest addition of the journal science. Welcome to the program.Thank you.You are a cancer researcher, not a DNA site is. What questions were you trying to answer ?We were working on a virus to kill tumor cells. Certain genes are lost. They grow out of control. We found that we could turn off the jeans and it turned off the cancer cells but did it in a way that could not be explained by the textbook models and structures of DNA. The more we looked at it, I started reading textbooks and realized, these are cartoon models based on studying DNA in a test tube. They had never seen this in the cell. Those are the key structures of DNA that determine if the jeans can be accessed and used. The mystery has been that in the cell, there are two measures of DNA that has to be canned after -- can acted. There has to be compaction. That is why the DNA is not your destiny. One structure that determines if it can be accessed and used, it gets folded into structures but we have never seen what they are. For the first time, we can see the fine structures of DNA, 147 base pairs inside a single unit cell. It is like a journey to the center of the earth. It is an extraordinary vision of what is the structural code of the basis of life itself.The lab has produced a 3-D image of what is inside the cell.Right.Can you tell us how you went about doing that ?In previous work, we worked with Roger who passed away last year and also Mark Altman. We had probes to visualize proteins inside the cell. Based on network, we realized, I wonder if we could use a similar approach to visualize DNA. War who is a brilliant scientist,., what if we could find a DNA paint that could diffuse in the cell nuclear's. When you excite, you paint the DNA with a metal dusting that allows it to become visible in the microscope and with Mark's group who had developed ways of tilting the scan, it is a CT scan of the cell. That allowed us to reconstruct the 3-D structure of DNA as it bends and twist through the cell in the context in which a virus would see it. You get to take a journey and see the pixel -- physical structures for the first time. When we first saw the images, we were speechless.Dr. O'Shea, what you can see what is going on with the DNA, does it behave the way researchers thought it did ?Not at all. It was terrifying because we really had no horse in this race. We were coming from the point of view of cancer. I wanted to understand that structure. I thought it would look like it did enough textbooks. We were concerned. What was wrong. Then the more we looked at it, a textbook, it seems to be discreet structures but it would limit the different activities that you could have. It could only be a single stage. There was a huge variety of diversity across life. You need a bearable structure. It turns out that instead of folding, it is a spring necklace with beads so it can collapse and shape shift. That is why you can inherit the structures. That is why DNA is not your destiny. You inherit structures that are not encoded because it can collapse and remember that. That is the missing link to explain genotype to phenotype and why identical twins may actually have a slightly different structure. It is not all of the sequence. Now, we can see it.Bringing you back to the cancer, what is about being able to see the 3-D image that improves your ability to create drugs or treatments to fight cancer?That is the future. Life occurs in 3-D. Drugs bind two things. They see shapes. We know what the shapes are that we are trying to design drugs for. There are epigenetic drugs but they have been general because in diseases, you only want to turn on one gene if we know what this is shape and structure is, we can see it and we can rationally design drugs that change the structures. If you think about, the first diagnosis of cancer was in the 1800s. This is been a diagnostic test for cancers. It is pathologist looking at the nucleus. We can now see this. They are diagnostic. Structure determines functions. We have a single cell and we can see uniquely what the structures are that make the cancer different and you can personalize the drugs. That is looking to the future. It is quite mind blowing. That is where everything plays out.I am thinking with Dr. O'Shea, and associate pastor. The research our lab is the subject of the lead article in the latest edition of the journal science. Thank you so much.Thank you.
Salk and UC San Diego researchers have revealed for the first time the 3-D structure of DNA in living human cells. The discovery is expected to impact scientists ability to design drugs for hard to treat diseases.
Clodagh O'Shea is a cancer researcher and associate professor at the Salk Institute for Biological Studies. The research, out of her lab at Salk, is now the subject of the lead article in the latest edition of the journal Science.
To answer the question, "What is the fundamental structure of DNA?" O'Shea and her colleagues used a chemical dye to paint DNA inside a living cell with a metal polymer cast that when light is shined on it, the structure of the DNA can be viewed through an electron microscope.
When researchers first saw the reconstructed 3-D images of DNA chromatin at a 29,000x magnification, they thought they had made a mistake.
"When we first got the results, it wasn't like it was in the textbooks, which was kind of terrifying," O'Shea said. "Because we had no horse in the race — people had been working on this for decades — I simply wanted to know what (DNA chromatin) looked like. We then spent an awful long time wondering why it was wrong, why we were wrong. But then the more we looked and analyzed, we realized no, this really is what it looks like."
The discovery could lead scientists to develop more effective drugs, O'Shea said.
"What's amazing, is that what this dye does is paint the surface features of DNA chromatin and the nucleus and it's the surface features that potentially would be accessible to a drug so we have a surface map, right? So the question is, this is really looking to the future, but that's the kind of structure you need to design a drug," O'Shea said.
