Daily Archives: March 12, 2013

A six-sided structure formed by DNA strands. Researchers studied DNA structures such as this in an experiment at SLAC's Linac Coherent Light Source. Credit: Nadrian C. Seeman; Nature 461, 74-77, 2009

(Phys.org) The founding father of DNA nanotechnology a field that forges tiny geometric building blocks from DNA strands recently came to SLAC to get a new view of these creations using powerful X-ray laser pulses.

For decades, Nadrian C. "Ned" Seeman, a chemistry professor at New York University, has studied ways to assemble DNA strands into geometric shapes and 3-D crystals with applications in biology, biocomputing and nanorobotics.

He said the experiment conducted Feb. 7-11 at SLAC's Linac Coherent Light Source enabled his team for the first time to study the DNA structures using smaller crystals in solution at room temperature.

They want to find out whether they can analyze the structure of their samples more precisely in this natural state, as their previous work relied on larger, frozen samples and the freezing process can damage the DNA structures.

"I think we'll get some pretty exciting results," Seeman said during the last shift of the team's LCLS experiment. "I'm very excited by everything I have seen so far."

The DNA crystals were suspended in fluid and streamed across the path of the ultrabright, ultrashort LCLS X-ray laser pulses. Detectors captured images, known as diffraction patterns, produced as the X-ray light struck the crystals. The technique is known as X-ray nanocrystallography.

SLAC's Sebastien Boutet, an instrument scientist at the LCLS Coherent X-ray Imaging Department, said the DNA crystals used in the experiment measured up to about 2-5 microns, or 2-5 thousandths of a millimeter, in size. The crystals were largely triangular and were self-assembled from 3-D DNA objects, forming an ordered lattice. The first-of-its-kind experiment at LCLS involved "lots of trial and error to find the ideal way to prepare the samples," Boutet said.

The engineered structures exploit the natural chemical pairing of DNA to bond small strands of DNA together. The resulting structures can be used to build tiny mechanical boxes and programmable robots for targeting disease, for example.

Researchers can also use DNA engineering as a platform for studying other molecules, such as proteins, that are important to disease research and drug development but are difficult to crystallize, which makes them hard to visualize.

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X-ray laser explores new uses for DNA building blocks

Mar. 11, 2013 A team of USC scientists has identified a protein that can change DNA topology, making DNA twist up into a so-called "supercoil."

The finding provides new insight about the role of the protein -- known as mini-chromosome maintenance (MCM) -- in cancer cells, which have high levels of MCM.

Think about twisting one end of a rubber band while holding the other end still. After a few turns, it forms a neatly twisted rope. But if you keep on turning, the twisted band will twist back upon itself into an increasingly coiled-up knot. Similarly, a DNA molecule can be twisted and coiled to varying extents to form different "supercoiled" structures.

Chromosomal DNA forms different supercoiled structures to enable a number of important processes. It turns on or off some genes, while tuning up or down other genes. The study suggests that an overabundance of MCM in a cell may allow certain genes to be overexpressed, and tune down or turn off other important genes, causing the cell to grow out of control and become cancerous.

Chromosomal DNA structure is very important for regulating gene expression of a cell, and thus the physiological status of the cell. Changing DNA topology is one effective way of controlling chromosomal DNA structure. The discovery of MCM's ability to change DNA topology offers a totally new perspective to MCM's role in gene regulation and cancer," said Xiaojiang Chen, professor of molecular biology at the USC Dornsife College of Letters, Arts and Sciences, and corresponding author of the study.

Chen worked with fellow USC professor Susan Forsburg and USC graduate students Ian M. Slaymaker, Yang Fu and Nimna Ranatunga; as well as Daniel B. Toso and Z. Hong Zhou of UCLA and Aaron Brewster of UC Berkeley. Their study was published online by Nucleic Acids Research on Jan. 29.

Chen and his team found that MCM proteins form a filament that looks much like a wide tube, through which the DNA strand spirals its way along the inner tube wall. Inside of the tube is a wide spiral path that has a strong positive electrical charge.

"Such a striking feature is unusual," said Chen. Who is also a member of the USC Norris Cancer Center. "When you see that, you know it must have a special function." Indeed, it turns out that the positively charged spiral path attracts and binds to the DNA strand, which has a negatively charged phosphate backbone.

Holding the DNA tightly to the spiral path inside the helical filament tube causes the DNA double-helix to change structure, creating supercoils. Future research by the team will explore how the DNA topology changes caused by MCM impacts cancer cell formation as well as its utility in cancer therapy.

This research was funded by the National Institutes of Health, grant numbers GM080338, AI055926, GM071940 and GM059321.

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Protein abundant in cancerous cells causes DNA 'supercoiling'

Public release date: 11-Mar-2013 [ | E-mail | Share ]

Contact: Maria Hrynkiewicz maria@versita.com 48-660-476-421 Versita

Many Europeans are fretting these days over what they eat, and whether horse meat might have adulterated their pork chops. Food fraud has been dominating headlines globally - calling for new policies in law enforcement and more robust methods for successful food identification and authentication. As companies and manufacturers resort to fraudulent practices to extract more cash from the gullible public, it is estimated that up to 7% of the consumer supply chain contains hidden ingredients (i.e. not disclosed on the label). And while all too often policymakers seem oblivious to the problem, the growing awareness of plain criminal activity in food supply has stimulated an increase in published research on animal DNA testing, either for the identification of species or for the genetic linkage of a sample to a particular organism.

The conventional methodologies employed for the determination of species origin in meat products have predominantly applied molecular methods of immunochemical, electrophoretic and chromatographic analysis of proteins. For those cases where reliance on morphological characteristics is impractical or impossible, scientists offer now novel techniques allowing the identification of species specific DNA sequences. Among these is a technique that relies on the much debated DNA barcoding - developed by researchers from the Government Laboratory in Hong Kong who have come up with a method that permits DNA detection of the fraudulent substitution of commercial deer products, regardless of their physical state, so that identification by morphology (form) is not required.

Deer meat has come a long way as an alternative to pork and beef. But it has continued to catch up with consumers steadily if slowly over the last decade, mainly due to its nutritive and therapeutic values but also versatile serving methods. And while venison is low in fat and high in protein, iron, zinc, selenium, vitamin E and omega-3 fatty acids - adding up to one healthy meal in view of recent scams, it has become vital to provide tenable methods of effective deer meat verification.

The article published recently in DNA Barcodes (http://www.versita.com/dnabra), an open access journal by Versita, describes the protocol set up by Dr. W.M. Sin and Dr. Y.K. Tam - to examine whether DNA methods alone suffice to detect fraudulent substitution of commercial deer products or, whether any additional protocols are necessary to detect fraudulent substitution of cattle and water buffalo tendons (HK$50-80) for deer tendons (HK$280-640). The research confirmed that no other method proves as efficient and straightforward as the use of DNA barcodes, which are sufficient on their own to detect such substitution for deer in all tendon products, except for glue. Furthermore, the research findings permit DNA detection of fraudulent substitution of commercial deer products, regardless of their physical condition.

The attractiveness of this method lies in its utility. Commenting on the research, Prof. Jan Pawlowski, from the Department of Genetics & Evolution at University of Geneva, Switzerland, says: "The authors did an excellent work, offering a robust, solid and viable molecular tools to identify deer DNA even in highly processed products. This is a new example showing the importance of DNA barcoding for traceability of commercial products".

The method may well be embraced by law enforcement authorities and forensic scientists as an inexpensive alternative that only requires standard laboratory techniques for handling DNA. The move helps to combat the widespread mislabeling of deer, which results in cheaper meat being sold as a more expensive deer variety. It also opens a prospect for more in-depth research into other food supplies, and the roll-out of new technology that would allow a systematic use of barcoding. With the new food scandals unraveling on a daily basis, DNA barcodes have a great potential to prevent and combat wildlife crime.

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Full text available: http://www.degruyter.com/view/j/dna.2012.1.issue/dna-2013-0001/dna-2013-0001.xml?format=INT

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DNA barcoding alone sufficient to detect fraudulent deer products

San Francisco, March 12 (IANS) Scientists have shown that DNA length can help predict lifespan in patients with cardiac disease, says a new study.

Can the length of strands of DNA in patients with heart disease predict their life expectancy? Researchers from the Intermountain Heart Institute at Intermountain Medical Center in Salt Lake City, who studied the DNA of more that 3,500 patients with heart disease, say it can.

In the study, presented March 9 at the American College of Cardiology's Annual Scientific Session here, the researchers were able to predict survival rates among patients with heart disease based on the length of strands of DNA found on the ends of chromosomes known as telomeres -- the longer the patient's telomeres, the greater the chance of living a longer life.

Previous research has shown that telomere length can be used as a measure of age, but these expanded findings suggest that telomere length may also predict the life expectancy of patients with heart disease.

Telomeres protect the ends of chromosome from becoming damaged. As people get older, their telomeres get shorter until the cell is no longer able to divide.

Shortened telomeres are associated with age-related diseases such as heart disease or cancer, as well as exposure to oxidative damage from stress, smoking, air pollution, or conditions that accelerate biologic aging, reports Science Daily.

"Our research shows that if we statistically adjust for age, patients with longer telomeres live longer, suggesting that telomere length is more than just a measure of age, but may also indicate the probability for survival. Longer telomere length directly correlate with the likelihood for a longer life -- even for patients with heart disease," said John Carlquist, one of the researchers.

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DNA length linked to lifespan

In addition to building organisms and storing Shakespeares sonnets, DNA could also keep your favorite nerd-shirt from going up in flames.

Normally, cotton fabrics are highly flammable.But when scientists tried to set fire to cottoncoated with herring sperm DNA, the fabric refused to burn, the team reported in Journal of Materials Chemistry A.

DNA can be considered as a natural flame retardant and suppressant, said materials scientistGiulio Malucelli, whose lab at Italys Politecnico di Torino, Alessandria branch,tested the fire-retardant properties of DNA. It could work also on other synthetic fabrics, or thin or thick plastic films.

Malucellis lab tested whether the macromolecule could stop fires by using DNA extracted from herring sperm. The team dissolved the DNA in water, coated cotton fabrics with it, let them dry, and tried to light them up. The coating behaved similarly to ammonium polyphosphate, a flame retardant commonly used on polymeric materials such as polyurethanes (found in foams and Spandex) and polyolefins (found in flexible foams and electrical insulation).

DNAs chemical structure makes it ideal for the flame-stopping job. When heated, its phosphate-containing backbone produces phosphoric acid, which chemically removes water from cotton fibers while leaving behind a flame-resistant, carbon-rich residue. The nitrogen-containing bases release ammonia which dilutes flammable gases and inhibits combustion reactions and can act as blowing agents, which help turn the carbon-rich deposits into a slow-burning protective layer. Ultimately, these ingredients stop combustion by forming either a carbon-rich foam, or a protective, glassy carbon coating called char.

I was surprised, and then as I looked at the chemical structure of DNA, it started to become obvious why DNA works as a fire retardant,said Alexander Morgan, a flame retardant materials scientist at the University of Dayton Research Institute.You probably get a mix of the glassy carbon and carbon foam forming during burning of DNA on the fabric.

As a naturally occurring compound, DNA could conceivably be a good green alternative to conventional flame retardants, with a few modifications. First, the cost needs to come down, Morgan says, since its between three and five times more expensive than current chemicals. And the toxicological profile needs to be determined. Though its a natural substance, Morgan notes the possibility that other organisms including the wearer of DNA-coated attire could pick up foreign fragments as the DNA breaks down.

Malucelli thinks thats unlikely. To the best of our knowledge, DNA is not toxic at all, Malucelli said. Its application as flame retardant should not be harmful.

Perhaps most problematically, for the time being, you cant wash a DNA-coated nerd-shirt. The coating is not yet water resistant and will rinse off in the wash. So far, scientists havent yet worked out how to make the treatment more permanent. But Malucelli and his colleagues are investigating a chemical cross-linking strategy, which would bind individual DNA strands to the fabric and to each other, creating a giant, insoluble matrix.

This is a key open issue that has to be solved, he said.

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Can't Burn This: DNA Shows Surprising Flame-Retardant Properties