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Scooped by Dr. Stefan Gruenwald!

Gene therapy restores sense of smell in mice

Gene therapy restores sense of smell in mice | Amazing Science |

A groups of researchers, lead by the University of Michigan, looked at mice with a mutation in their Ift88 gene, which meant they struggled to produce cilia and could not smell. The group created a virus which was capable of infecting cells with a working version of the Ift88 gene. This was injected into the nose on three consecutive days. This was able to restore the cilia and a sense of smell.

Prof Philip Beales from University College London was involved in the study. He told the BBC: "It is a proof of concept that has shown we can get that gene back into these cells, produce the right protein, produce cilia and function as expected. He said the mice were then able to use their sense of smell to seek out food. However, it is hoped a similar approach could be used for other symptoms of the disorders.

Dr James Battey, director of the US National Institute on Deafness and Other Communications Disorders which part funded the research said: "These results could lead to one of the first therapeutic options for treating people with congenital anosmia. "They also set the stage for therapeutic approaches to treating diseases that involve cilia dysfunction in other organ systems, many of which can be fatal if left untreated."

The study is published in Nature Medicine.

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Lucky star escapes black hole with minor damage

Lucky star escapes black hole with minor damage | Amazing Science |
Astronomers have gotten the closest look yet at what happens when a black hole takes a bite out of a star—and the star lives to tell the tale.

We may think of black holes as swallowing entire stars—or any other object that wanders too close to their immense gravity. But sometimes, a star that is almost captured by a black hole escapes with only a portion of its mass torn off. Such was the case for a star some 650 million light years away toward Ursa Major, the constellation that contains the "Big Dipper," where a supermassive black hole tore off a chunk of material from a star that got away.

Astronomers at The Ohio State University couldn't see the star itself with their All-Sky Automated Survey for Supernovae (ASAS-SN, pronounced "assassin"). But they did see the light that flared as the black hole "ate" the material that it managed to capture.

In a paper to appear in the Monthly Notices of the Royal Astronomical Society, they report that the star and the black hole are located in a galaxy outside of the newly dubbed Laniakea Supercluster, of which our home Milky Way Galaxy is a part.

If Laniakea is our galactic "city," this event—called a "tidal disruption event," or TDE— happened in our larger metropolitan area. Still, it's the closest TDE ever spotted, and it gives astronomers the best chance yet of learning more about how supermassive black holes form and grow.

ASAS-SN has so far spotted more than 60 bright and nearby supernovae; one of the program's other goals is to try to determine how often TDEs happen in the nearby universe. But study co-author Krzysztof Stanek, professor of astronomy at Ohio State, and his collaborators were surprised to find one in January 2014, just a few months after ASAS-SN's four telescopes in Hawaii began gathering data.

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Terrestrial Return Vehicle to provide parcel post for the ISS

Terrestrial Return Vehicle to provide parcel post for the ISS | Amazing Science |

So much attention is paid to how to get into space that we often forget that getting back can be just as difficult. For example, getting experiment samples back from the International Space Station (ISS) is a logistical nightmare. Intuitive Machines' Terrestrial Return Vehicle (TRV) system may change that by making sending small payloads back to Earth as easy as mailing a parcel.

Getting samples back from the ISS currently means hitching a ride on a returning cargo or crew ferry craft, but this happens only a few times a year with every ounce already spoken for. That may be okay for most items, but what about the ones that can't wait?

The Terrestrial Return Vehicle (TRV) is a commercial service being developed by Intuitive Machines and NASA as part of a project under the Center for the Advancement of Science in Space (CASIS), which is responsible for installing the TRV on the space station and non-flight systems. It's designed to return small samples on demand from the ISS on the same day, and is suitable for critical and perishable materials that can't wait for the next ship home.

The TRV system is designed to be stored in the habitable volume of the ISS until required. When loaded up with its cargo, the TRV is placed in the Japanese Experiment Module (JEM) airlock, where the Cyclops ejection mechanism and the JEM Robotic Manipulator System are used to deploy it. Once released from the ISS, the TRV's guidance and propulsion systems take over and execute a controlled reentry maneuver before the craft's airfoil is deployed and it touches down at its designated spaceport.

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New single-cell analysis: Tiny dual-channel quartz needle for nanoelectrospray ionization mass spectrometry

New single-cell analysis: Tiny dual-channel quartz needle for nanoelectrospray ionization mass spectrometry | Amazing Science |

By inserting this tiny dual-bore needle into a living single cell, researchers can send its contents to a mass spectrometer for analysis.

With a new mass spectrometry technique, researchers can survey the suite of small molecules inside a single cell by inserting a tiny probe. The method requires little sample preparation that would affect a cell’s chemistry and can analyze the contents of an individual cell in about three minutes (Anal. Chem. 2014, DOI: 10.1021/ac5029038).

Just as no two people are identical, no two cells are the same, says Zhibo Yang, a chemist at the University of Oklahoma who developed the new technique with his colleagues. Understanding biochemical differences between cells can help researchers pinpoint the hallmarks of cancer or neurological disease and investigate how individual cells respond to drugs. In 2012, the National Institutes of Health allotted $90 million to support research into this area through its Single Cell Analysis Program.

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Unusual Distribution of Organics Found in Titan’s Atmosphere

Unusual Distribution of Organics Found in Titan’s Atmosphere | Amazing Science |

A new mystery of Titan has been uncovered by astronomers using their latest asset in the high altitude desert of Chile. Using the now fully deployed Atacama Large Millimeter Array (ALMA) telescope in Chile, astronomers moved from observing comets to Titan. A single 3 minute observation revealed organic molecules that are askew in the atmosphere of Titan. The molecules in question should be smoothly distributed across the atmosphere but they are not.

The Cassini/Huygens spacecraft at the Saturn system has been revealing the oddities of Titan to us, with its lakes and rain clouds of methane and an atmosphere thicker than Earth’s. But the new observations by ALMA of Titan underscore how much more can be learned about Titan and also how incredible the ALMA array is.

The ALMA astronomers called it a “brief 3 minute snapshot of Titan.” They found zones of organic molecules offset from the Titan polar regions. The molecules observed were hydrogen isocyanide (HNC) and cyanoacetylene (HC3N). It is a complete surprise to the astrochemist Martin Cordiner, from NASA Goddard Space Flight Center in Greenbelt, Maryland. Cordiner is the lead author of the work published in the latest release of Astrophysical Journal Letters.

The NASA Goddard press release states, “At the highest altitudes, the gas pockets appeared to be shifted away from the poles. These off-pole locations are unexpected because the fast-moving winds in Titan’s middle atmosphere move in an east–west direction, forming zones similar to Jupiter’s bands, though much less pronounced. Within each zone, the atmospheric gases should, for the most part, be thoroughly mixed.”

When one hears there is a strange, skewed combination of organic compounds somewhere, the first thing to come to mind is life. However, the astrochemists in this study are not concluding that they found a signature of life. There are, in fact, other explanations that involve simpler forces of nature. The Sun and Saturn’s magnetic field delivers light and energized particles to Titan’s atmosphere. This energy causes the formation of complex organics in the Titan atmosphere. But how these two molecules – HNC and HC3N came to have a skewed distribution is, as the astrochemists said, “very intriguing.” Cordiner stated, “This is an unexpected and potentially groundbreaking discovery… a fascinating new problem.”

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Chamber of secrets: How cells organise themselves influences their ability to communicate

Chamber of secrets: How cells organise themselves influences their ability to communicate | Amazing Science |

Durdu, a PhD student in Darren Gilmour’s lab at EMBL, found this behaviour in specific groups of cells in the zebrafish: the cells that will develop into the animal’s ‘lateral line’, a series of ear-like organs along the fish’s flank that allow it to sense changes in water pressure. As a zebrafish develops, a mass of cells moves along the developing animal’s side. At the point where one of these organs should form, a group of cells at the rear assembles into a huddle and stops, eventually developing into the organ. The rest of the cells, meanwhile, have moved on, until another group stops to form another organ, and so on. The cells that group together and stop to form the future organ also change shape, going from flat, crawling cells to upright, tear-shaped cells that come together like cloves in a bulb of garlic. Durdu found that these ‘garlic cloves’ huddle around a shared space, or lumen, in which they trap a molecule cells use to communicate: FGF. 

“Normally, FGF acts as a long-range communication signal. In the lateral line, we find that most of this signal is normally just wafting over the cells’ heads,” says Gilmour. “But when cells get together and huddle they can trap and concentrate this signal in their shared lumen, and make a decision that the others can’t: they stop moving.”

The EMBL scientists found that, by enabling a group of cells to increase the concentration of FGF they are in contact with, the shared lumen plays a critical role in determining when and where the huddles stop moving. When the scientists increased the concentration of FGF, cell huddles came to a standstill more abruptly, forming organs that were closer together. And when they decreased the level of FGF, huddles continued to migrate for longer and formed organs that were further apart.

“All epithelial cells – and that’s the cells that make up most of the organs in our bodies – can do this, so you could imagine that this type of local chamber could be forming transiently in many different parts of the body, whenever cells need to self-organise and communicate,” Gilmour says.

When the scientists broke up cell huddles in their zebrafish embryos, FGF leaked out. When this happens the cells in a group are no longer able to communicate efficiently, leading the scientists to wonder if this influence of organisation on communication could play a role in wound repair. When our skin is scratched, cells that were standing upright ‘lie down’ and start crawling – in essence, local huddles break up and cells change their behaviour. Another situation where cells may be huddling to communicate within a group, Gilmour and Durdu posit, is in organoids – self-assembled organ-like structures grown in the lab, which start by forming a common lumen.

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Tiny Creatures Come to Life in Nikon's 'Small Worlds' Photo Contest

Tiny Creatures Come to Life in Nikon's 'Small Worlds' Photo Contest | Amazing Science |

Without access to a microscope or a sophisticated zoom lens, most people don't get to see plant pores and cricket tongues up close. But the entrants in the 2014 Nikon Small World photography contest offer an intimate look at tiny realms rarely seen outside of a lab. The judges of the annual contest will reveal their top picks on Oct. 30, but the following images are a sample of the submissions. More information can be found on the contest website.

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Noncovalent, Self-Assembled, Robust, Porous Material That Adsorbs Greenhouse Gas

Noncovalent, Self-Assembled, Robust, Porous Material That Adsorbs Greenhouse Gas | Amazing Science |

Researchers from the Department of Chemistry at the University of Houston have created noncovalent organic frameworks, a new type of porous material that overcomes some barriers in the development of porous material technologies.  The new wonder material is highly processable, self-assembled, possessing of a superstructure with large, 16 angstrom pores (Figure above).  The material has a high affinity for hydrocarbons suggesting applications for use as an energy storage substrate.  In addition, the material also captures CFCs and fluorocarbons, both potent greenhouse gas species.  The capture capacity is up to 75% of the original weight.

The field of porous materials has experienced two other, prior twin advances in the area of metal-organic and covalent organic frameworks though they are plagued by the problem of low processability as the extended crystalline structure makes them impossible to dissolve without decomposition.

Remarkably, the building block of the noncovalent porous material is a single molecule trispyrazole, which stack and self-assemble into a large, porous, crystal-like configuration.  The author characterizes the pores as “infinite one-dimensional channels protruding throughout the crystal along the crystallographic c axis”.  The interior “lining” of the channels is arrayed with fluorines.

The entire super structure is stabilized by noncovalent hydrogen bonds and “pi-pi” stacking – hallmarks of a “supramolecular” material.  H-bonds and pi-interactions  are considered “weak” associations between molecules, but by virtue of the sheer number and surface area of interactions, the material turns out to be thermally very stable (up to 250 degrees C) and resistant to solvents, acids and bases.  Engineers interested in manipulating the material would find most interesting that its solubility in DMSO can be tuned by temperature.

Of great interest in porous materials is measurement of the “effective surface area” in the pores, for a given weight of the porous material.  A common measure of the surface area is the Brunauer–Emmett–Teller surface area.  Using nitrogen adsorption measurements the surface area was determined to be 1,159 m2 g−1.  For comparison activated charcoal used in water filters has a surface area of about 500 m2 g−1.  The high surface area is the reason for the high capture weight proportion (75%).

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RCas9: A Programmable RNA Editing Tool Based on CRISPR-CAS

RCas9: A Programmable RNA Editing Tool Based on CRISPR-CAS | Amazing Science |

A powerful scientific tool for editing the DNA instructions in a genome can now also be applied to RNA, the molecule that translates DNA's genetic instructions into the production of proteins. A team of researchers with Berkeley Lab and the University of California (UC) Berkeley has demonstrated a means by which the CRISPR/Cas9 protein complex can be programmed to recognize and cleave RNA at sequence-specific target sites. This finding has the potential to transform the study of RNA function by paving the way for direct RNA transcript detection, analysis and manipulation.

A team led by Jennifer Doudna, biochemist and leading authority on the CRISPR/Cas9 complex, showed how the Cas9 enzyme can work with short DNA sequences known as "PAM," for protospacer adjacent motif, to identify and bind with specific site of single-stranded RNA (ssRNA). They are designating this RNA-targeting CRISPR/Cas9 complex as RCas9.

In recent years, the CRISPR/Cas complex has emerged as one of the most effective tools for doing this. CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, is a central part of the bacterial immune system and handles sequence recognition. Cas9 - Cas stands for CRISPR-assisted - is an RNA-guided enzyme that handles the sniping of DNA strands at the specified sequence site. Together, CRISPR and Cas9 can be used to precisely edit the DNA instructions in a targeted genome for making desired types of proteins. The DNA is cut at a specific location so that old DNA instructions can be removed and/or new instructions inserted. Until now, it was thought that Cas9 could not be used on the RNA molecules that transcribe those DNA instructions into the desired proteins.

"Just as Cas9 can be used to cut or bind DNA in a sequence-specific manner, RCas9 can cut or bind RNA in a sequence-specific manner," says Mitchell O'Connell, a member of Doudna's research group and the lead author of a paper in Nature that describes this research titled "Programmable RNA recognition and cleavage by CRISPR/Cas9." Doudna is the corresponding author. Other co-authors are Benjamin Oakes, Samuel Sternberg, Alexandra East Seletsky and Matias Kaplan.

In an earlier study, Doudna and her group showed that the genome editing ability of Cas9 is made possible by presence of PAM, which marks where cutting is to commence and activates the enzyme's strand-cleaving activity. In this latest study, Doudna, Mitchell and their collaborators show that PAMmers, in a similar manner, can also stimulate site-specific endonucleolytic cleavage of ssRNA targets. They used Cas9 enzymes from the bacterium Streptococcus pyogenes to perform a variety of in vitro cleavage experiments using a panel of RNA and DNA targets.

"While RNA interference has proven useful for manipulating gene regulation in certain organisms, there has been a strong motivation to develop an orthogonal nucleic-acid-based RNA-recognition system such as RCas9," Doudna says. "The molecular basis for RNA recognition by RCas9 is now clear and requires only the design and synthesis of a matching guide RNA and complementary PAMmer."

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Using monoclonal antibodies produced in plants to fight off a lethal virus like Ebola

Using monoclonal antibodies produced in plants to fight off a lethal virus like Ebola | Amazing Science |

Kevin Whaley, the CEO at Mapp Bio isn't much given to publicly discussing ZMapp, the remarkable new treatment for Ebola, at all. At a time when every public biotech company with a preclinical program for Ebola is clamoring for attention, Whaley has given precious few interviews. And when he has talked about ZMapp, he's been careful to say that the company doesn't know whether it works and has lots more work to do. If anything, the air of mystery has only heightened the lurid 24/7 cable news attention given to ZMapp, which could help revolutionize the way in which outbreaks are treated in years to come.

ZMapp is a cocktail therapy made up of antibodies that Mapp's small team of 9 has assembled into a single treatment. For a vaccine, investigators would work on delivering antibodies that would prime the human immune system to fight off a lethal virus like Ebola. But for people who are already infected, facing about a 50% mortality rate, this new approach has the potential to provide a powerful and immediate response.

ZMapp includes antibodies that were generated in mouse models exposed to an Ebola protein, then "humanized" to prevent rejection, transferred to tobacco plants through a benign plant virus--or vector--and grown in the genetically engineered tobacco leaves, which are harvested to produce the therapy. The cocktail includes antibodies licensed from Defyrus and USAMRIID, all drawn by the notion that a cocktail therapy would prove to be a patient's best shot at survival. That combination of antibodies in the cocktail represents the culmination of 10 years of work, and it was only arrived at in January.

The NIH unintentionally helped get the media frenzy started when they supplied a few doses to treat two Western Ebola victims, who appear to have responded very well and are now recovering. In a matter of weeks, Mapp nailed another impressive primate study, saving all the infected animals from a likely death. The U.S. government followed up with a contract worth up to $42 million to speed up work on production. The helter-skelter development effort was pointed down the path to a quick approval as Mapp's slow-motion progress of recent years collided with the fact that only one Ebola treatment was in the clinic, and that one had been under a clinical hold at the FDA before regulators immediately cleared it for production.

Enormous logistical issues remain. In addition to the clinical program that's needed to fully test the safety and efficacy of the treatment in humans, the treatment would need to be made in large quantities in order to combat the worst outbreak health officials have seen since Ebola first appeared in 1976. Currently, only one biologic is approved for manufacturing in plants, and that is Protalix's ($PLXGaucher'sdrug, which is made in plant cells. Kentucky BioProcessing currently makes ZMapp, using vector technology from Icon Genetics. But even with a huge effort, KBP would need months to scale up production.

South African officials say they have been approached about building a facility, which would take time, while Protalix has had to walk back some statements implying that they could adapt their manufacturing process to churn out ZMapp.

ZMapp™ is the result of a collaboration between Mapp Biopharmaceutical, Inc. and  LeafBio (San Diego, CA), Defyrus Inc (Toronto, Canada), the U.S. government and the Public Health Agency of Canada (PHAC). ZMapp™ is composed of three “humanized” monoclonal antibodies manufactured in plants, specifically Nicotiana. It is an optimized cocktail combining the best components of MB-003 (Mapp) and ZMAb (Defyrus/PHAC).

ZMappTM was first identified as a drug candidate in January 2014 and has not yet  been evaluated for safety in humans. As such, very little of the drug is currently available. Any decision to use an experimental drug in a patient would be a decision made by the treating physician under the regulatory guidelines of the FDA.

Mapp and its partners are cooperating with appropriate government agencies to increase production as quickly as possible. Two partnerships were crucial to us in the development of the plant system for ZMappTM: Icon Genetics AG (Halle, Germany) and Kentucky BioProcessing (KBP,
Owensboro, KY). Icon pioneered vectors for engineering Nicotiana to produce biopharmaceuticals. KBP specializes in GMP manufacturing of therapeutic proteins in Nicotiana.

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6 mKelvin: The drive to create the coldest cubic meter in the universe

6 mKelvin: The drive to create the coldest cubic meter in the universe | Amazing Science |

An international team of scientists recently set a world record by cooling a copper vessel with a volume of a cubic meter down to a temperature of 6 milliKelvins—or -273.144 degrees Celsius. It was the first experiment to chill an object so large this close to absolute zero.

The collaboration, called CUORE (Cryogenic Underground Observatory for Rare Events), involves 130 scientists from the United States, Italy, China, Spain, France, and other countries. It is based at the underground Gran Sasso National Laboratory of the Instituto Nazionale di Fisica Nucleare, in Italy.

"This is a major technological achievement," said Karsten Heeger, a professor of physics at Yale and director of Yale's Arthur W. Wright Laboratory. CUORE is part of the new experimental program in neutrinos and dark matter pursued at the Wright Lab.

Yale physicists are building and testing instrumentation that will be used at temperatures of 10mK in the experiment's cryostat, which is the chilled chamber. Reina Maruyama, an assistant professor of physics, is one of the original proponents for the US involvement in CUORE and is a coordinator of its data analysis

"In collaboration with the University of Wisconsin, we have developed a detector calibration system that will deploy radioactive sources into the coldest region of the cryostat and characterize our detectors," Heeger said.

Once the CUORE experiment is fully operational, it will study important properties of neutrinos, the fundamental, subatomic particles that are created by radioactive decay and do not carry an electrical charge.

Specifically, the experiment will look at a rare process called neutrinoless double-beta decay. The detection of this process would let researchers demonstrate, for the first time, that neutrinos and antineutrinos are the same—thereby offering a possible explanation for the abundance of matter, rather than anti-matter, in the universe.

The experiment uses heat-sensitive detectors that operate in extremely cold temperatures. "It poses a unique challenge," Heeger said. "We are trying to detect a minuscule amount of heat from nuclear decay, but need to know this very precisely. The detector calibration will tell us if we see the heat from double-beta decay or environmental backgrounds."

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Tarantula toxin is used to report electrical activity inside live cells

Tarantula toxin is used to report electrical activity inside live cells | Amazing Science |

Crucial experiments to develop a novel probe of cellular electrical activity were conducted in the Neurobiology course at the Marine Biological Laboratory (MBL) in 2013. Now, that optical probe, which combines a tarantula toxin with a fluorescent compound, is introduced in a paper in the Proceedings of the National Academy of Sciences.

The lead authors of the paper are Drew C. Tilley of UC-Davis and the late Kenneth Eum, a Ph.D. candidate at UC-Davis and teaching assistant in the MBL Neurobiology course. The probe takes advantage of the potent ability of tarantula toxin to bind to electrically active cells, such as neurons, while the cells are in a resting state. The team discovered that a trace amount of toxin combined with a fluorescent compound would bind to a specific subset of voltage-activated proteins (Kv2-type potassium ion channels) in live cells. The probe lights up cell surfaces with this ion channel, and the fluorescent signal dims when the channel is activated by electrical signals.

This is the first time that researchers have been able to visually observe these ion channels "turning on" without first genetically modifying them. All that is required is a means to detect probe location, suggesting that related probes could potentially one day be used to map neural activity in the human brain.

"This is a demonstration, a prototype probe. But the promise is that we could use it to measure the activity state of the electrical system in an organism that has not been genetically compromised," says senior author Jon Sack, an assistant professor in the departments of Physiology and Membrane Biology at UC-Davis. Sack is a faculty member in the MBL Neurobiology course.

Since the probe binds selectively to one of the many different kinds of ion channels, it can help scientists disentangle the function of those specific channels in neuronal signaling. This can, in turn, lead to the identification of drug targets for neurological diseases and disorders.

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Bio-Inspired ‘Nano-Cocoons’ Offer Targeted Drug Delivery Against Cancer Cells

Bio-Inspired ‘Nano-Cocoons’ Offer Targeted Drug Delivery Against Cancer Cells | Amazing Science |

Biomedical engineering researchers have developed a drug delivery system consisting of nanoscale “cocoons” made of DNA that target cancer cells and trick the cells into absorbing the cocoon before unleashing anticancer drugs. The work was done by researchers at North Carolina State University and the University of North Carolina at Chapel Hill.

“This drug delivery system is DNA-based, which means it is biocompatible and less toxic to patients than systems that use synthetic materials,” says Dr. Zhen Gu, senior author of a paper on the work and an assistant professor in the joint biomedical engineering program at NC State and UNC Chapel Hill.

“This technique also specifically targets cancer cells, can carry a large drug load and releases the drugs very quickly once inside the cancer cell,” Gu says. “In addition, because we used self-assembling DNA techniques, it is relatively easy to manufacture,” says Wujin Sun, lead author of the paper and a Ph.D. student in Gu’s lab.

Each nano-cocoon is made of a single strand of DNA that self-assembles into what looks like a cocoon, or ball of yarn, that measures 150 nanometers across. The core of the nano-cocoon contains the anticancer drug doxorubicin (DOX) and a protein called DNase. The DNase, an enzyme that would normally cut up the DNA cocoon, is coated in a thin polymer that traps the DNase like a sword in a sheath.

The surface of the nano-cocoon is studded with folic acid ligands. When the nano-cocoon encounters a cancer cell, the ligands bind the nano-cocoon to receptors on the surface of the cell – causing the cell to suck in the nano-cocoon.

Once inside the cancer cell, the cell’s acidic environment destroys the polymer sheath containing the DNase. Freed from its sheath, the DNase rapidly slices through the DNA cocoon, spilling DOX into the cancer cell and killing it.

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Paper-based synthetic gene networks could enable rapid detection of Ebola and other viruses

Paper-based synthetic gene networks could enable rapid detection of Ebola and other viruses | Amazing Science |

Synthetic gene networks hold great potential for broad biotechnology and medical applications, but so far they have been limited to the lab. A study published by Cell Press October 23rd in the journal Cell reveals a new method for using engineered gene circuits beyond the lab, allowing researchers to safely activate the cell-free, paper-based system by simply adding water. The low-cost, easy-to-use platform could enable the rapid detection of different strains of deadly viruses such as Ebola.

"Our paper-based system could not only make tools currently only available in laboratory readily fieldable, but also improve the development of new tools and the accessibility of these molecular tools to educational programs for the next generation of practitioners," says senior study author James Collins of the Wyss Institute for Biological Inspired Engineering at Harvard University.

The field of synthetic biology aims to re-engineer the molecular components of the cell to harness the power of biology. To accomplish this goal, researchers have designed synthetic gene networks that can control the activity of genes and recognize nucleic acids and small molecules. However, this technology has been restricted to the lab, in part because of biosafety concerns associated with cell-based systems and because the reactions involved have not been practical for field use.

Collins and his team overcame these hurdles by developing a cell-free, paper-based system suitable for use outside the lab. To test the clinical relevance of their method, the researchers developed sensors capable of detecting RNA molecules made from genes that allow bacteria to survive antibiotics, as well as RNA molecules encoding proteins from two different strains of the highly deadly Ebola virus. When freeze-dried onto paper, the sensors quickly detected the presence of these RNA molecules, demonstrating the usefulness of the approach for diagnostic purposes.

"Considering the projected cost, reaction time, ease of use, and no requirement for laboratory infrastructure, we envision paper-based synthetic gene networks significantly expanding the role of synthetic biology in the clinic, global health, industry, research, and education," Collins says.

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Integrating laser diode and ultrasound transducer array to build compact medical imaging device

Integrating laser diode and ultrasound transducer array to build compact medical imaging device | Amazing Science |

Scientists at the MIRA research institute, in collaboration with various companies, have developed a prototype of a handy device that combines echoscopy (ultrasound) with photoacoustics. Combining these two medical imaging technologies in a compact device is designed, among other things, to enable the amount of inflammation in rheumatic patients' joints to be measured more simply and precisely. The researchers expect that the technology will eventually also be able to play a role in detecting the severity of burns, skin cancer and furring of the arteries. The prototype is presented in the scientific journal Optics Express.

Echoscopy and photoacoustics are complementary medical imaging technologies. Photoacoustics involves sending brief laser pulses into the patient's body. When the laser light hits a blood vessel, for example, it is locally converted into heat, which causes a minor rise in pressure. This propagates through the body like a sound wave and can then be measured on the skin. Echoscopy involves sending ultrasound waves into the body: different tissues reflect them in different ways, and they too can then be detected on the skin. Whereas echoscopy provides an image of structures, photoacoustics can provide an image containing more functional information, such as the presence of blood.

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High-speed evolution in the lab: Geneticists evaluate cost-effective pool genome analysis

High-speed evolution in the lab: Geneticists evaluate cost-effective pool genome analysis | Amazing Science |

Life implies change. And this holds true for genes as well. Organisms require a flexible genome in order to adapt to changes in the local environment. Christian Schlötterer and his team from the Institute for Population Genetics at the University of Veterinary Medicine, Vienna study the genomes of entire populations. The scientists want to know why individuals differ from each other and how these differences are encoded in the DNA. In two review papers published in the journals Nature Reviews Genetics and Heredity, they discuss why DNA sequencing of entire groups can be an efficient and cost-effective way to answer these questions.   

DNA analysis has become increasingly efficient and cost-effective since the human genome was first fully sequenced in the year 2001. Sequencing a complete genome, however, still costs around US$1,000. Sequencing the genetic code of hundreds of individuals would therefore be very expensive and time-consuming. In particular for non-human studies, researchers very quickly hit the limit of financial feasibility.  

The solution to this problem is pool sequencing (Pool-Seq). Schlötterer and his team sequence entire groups of fruit flies (Drosophila melanogaster) at once instead of carrying out many individual sequencing reactions. While the resulting genetic information cannot be attributed to a single individual, the complete data set still provides important genetic information about the entire population.

In order to understand how organisms react to changes in the local environment, the genomes of entire populations can be analysed using Pool-Seq, before and after changed conditions. To do so, the researchers use the method of evolve and resequence (E&R). Schlötterer received an ERC Advanced Grant for this approach in 2012. E&R is a method in which the DNA of a group of individuals is sequenced.  After exposing the descendents of this group for several generations to a certain stress, such as high temperature, extreme cold or UV radiation, and the evolved group is then sequenced again. A comparison of the two data sets uncovers genes that have changed in response to the selective stress. The approach makes it possible, for example, to filter out the genes that are involved in a darker pigmentation in response to UV radiation. 

“Using this principle, we can perform evolution experiments at high speed. We are using this method to address a broad range of questions, ranging from the identification of genes which influence aging, or genes protecting against diseases and finally to understand the genetic changes which reduce the impact of climate change,” Schlötterer explains.

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Siberian thighbone data adjust time of human and Neanderthal interbreeding to around 50,000 years ago

Siberian thighbone data adjust time of human and Neanderthal interbreeding to around 50,000 years ago | Amazing Science |

New research on a 45,000-year-old Siberian thighbone has narrowed the window of time when humans and Neanderthals interbred to between 50,000 and 60,000 years ago, and has shown that modern humans reached northern Eurasia substantially earlier than some scientists thought.

Qiaomei Fu, a postdoctoral fellow at Harvard Medical School (HMS) and first author of a paper describing the research, said the sample had a long history before making its way into her hands.

The bone was found eroding out of a Siberian riverbank, but no one knows precisely where. The bone changed hands several times before finding its way to the Max Planck Institute for Evolutionary Anthropology in Germany, where Fu was working with professors Janet Kelso and Svante Pääbo. Fu put the finishing touches on the research after she started in the laboratory of David Reich, HMS genetics professor.

Carbon dating and molecular analysis filled in many of the blanks about the sample. Testing determined that the sample was from an individual who lived 45,000 years ago on a diet that included plants or plant eaters and fish or other aquatic life.

Reich and Fu said the sample was remarkable because of the extraordinary preservation of its DNA, which allowed Fu, using the latest techniques for ancient DNA analysis, to extract a high-quality genome sequence. The sequence, Reich said, is significantly higher in quality than most genome sequences of present-day people generated for analysis of disease risk.

The sequence revealed that the bone came from a modern human, a man whose remains are the oldest ever found and carbon-dated outside of Africa and the Middle East. Comparison to diverse humans around the world today showed that the man was a member of one of the most ancient non-African populations.

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Extremely high-resolution MRI: New MRI method detects single hydrogen atom

Extremely high-resolution MRI: New MRI method detects single hydrogen atom | Amazing Science |

For the first time, researchers have succeeded to detect a single hydrogen atom using magnetic resonance imaging, which signifies a huge increase in the technology's spatial resolution. In the future, single-atom MRI could be used to shed new light on protein structures.

Conventional magnetic resonance imaging (MRI), well-known from its use in hospitals, can typically resolve details of up to one tenth of a millimeter, for example in cross-sectional images of the human body. Together with colleagues at the University of Leipzig, researchers of ETH Zurich are working on massively increasing the resolution of the technique, with the goal of eventually imaging at the level of single molecules – demanding an over one million times finer resolution. By detecting the signal from a single hydrogen atom, they have now reached an important milestone toward such single-atom MRI.

The research team led by Christian Degen, Professor at the Laboratory for Solid State Physics, developed a different and vastly more sensitive measurement technique for MRI signals. In standard hospital instruments, the magnetisation of the atomic nuclei in the human body is inductively measured using an electromagnetic coil. "MRI is nowadays a mature technology and its spatial resolution has remained largely the same over the last ten years. Physical constraints preclude increasing the resolution much further," explains Degen. In their experiments, the ETH researchers measured the MRI signal with a novel diamond sensor chip using an optical readout in a fluorescence microscope.

The sensor consisted of an impurity in diamond known as the nitrogen-vacancy centre. In this case, two carbon atoms are missing in the otherwise regular diamond lattice, while one of them is replaced by a nitrogen atom. The nitrogen-vacancy centre is both fluorescent and magnetic, making it suitable for extremely precise magnetic field measurements.

For their experiment, the researchers prepared an approximately 2x2 millimeter piece of diamond such that nitrogen-vacancy centers formed only a few nanometers below the surface. By an optical measurement of the magnetisation, they were in several cases able to confirm the presence of other magnetic atomic nuclei in the immediate vicinity. "Quantum mechanics then provides an elegant proof of whether one has detected an individual nucleus, or rather a cluster of several hydrogen atoms," states Degen. The researchers also used the measured data to localize the hydrogen nuclei with respect to the nitrogen-vacancy centre with an accuracy of better than one angstrom

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What does the next generation telescope need to detect life?

What does the next generation telescope need to detect life? | Amazing Science |

Almost 2,000 extrasolar planets have been discovered to date and this number is constantly increasing. Yet, we still know little about these alien worlds, especially their atmospheres. The atmospheres of terrestrial exoplanets could betray the presence of life on the planet, sparking NASA's interest in acquiring the spectra that appears as starlight shines through these planetary atmospheres.

A paper by Timothy Brandt and David Spiegel, exo-planetary scientists at the Institute for Advanced Study, Princeton, details what is needed in a next generation telescope for it to be capable of detecting signatures of life in the atmospheres of alien planets. The paper has been published in the September issue of the journal Proceedings of the National Academy of Sciences.

Astronomers employ several different methods to study the atmospheres of gas giants that orbit close to their host stars. One such method involves comparing the spectrum of a star when a planet is transiting across the surface to a spectrum when the planet is out of transit. By comparing the spectra, it is possible to see which elements exist in the planet's atmosphere.

Methods like this still can't be used for terrestrial planets, as the height of the atmosphere engulfing a rocky planet is miniscule compared to that of a gas giant. Earth-like planets also orbit their stars at a larger distance, making it even more difficult to observe their atmospheres.

Observations of terrestrial planet atmospheres will require a specialized space mission that will use a coronograph to block out the blinding light of the star. While the James Webb Space Telescope, due to launch in 2018, will be capable of detecting elements in planetary atmospheres, it will still be limited to more massive planets.

"Our paper is an attempt to better define the requirements for a mission capable of detecting oxygen and water," says Brandt. "This is NASA's target, assuming technology developments in coronagraphy and adaptive optics permit it."

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New 'smart' material improves removal of arsenic from drinking water

New 'smart' material improves removal of arsenic from drinking water | Amazing Science |

Scientists have created a new material that can remove double the amount of arsenic from water than the leading material for water treatment. Arsenic is a toxic element found naturally in groundwater. Long-term exposure over a number of years to elevated concentrations of arsenate, the chemical form of arsenic in water, is associated with debilitating, and potentially fatal, illnesses including cancer, heart and lung disease, gastrointestinal problems and neurological disorders.

Arsenic-contaminated drinking water has been identified in many countries across the globe, including Bangladesh, Chile, Mexico, Argentina, Australia, USA and parts of the UK. Recent estimates suggest that more than 200 million people are unknowingly exposed to unsafe levels of arsenic in their drinking water.  

In a new study published inChemistry - A European Journal, scientists at Imperial College London have designed, tested and patented a new zinc-based material that can selectively bind to arsenate with strong affinity. The scientists hope this material could ultimately be used to improve quality of domestic water filters and reduce the amount of arsenic that people are exposed to, in areas with known or suspected high arsenic content.

In 2006 the World Health Organization issued guidelines defining safe concentration levels of arsenic as 10 parts per billion but several countries affected by arsenic-contaminated groundwater have legal concentration limits above this guideline and recent evidence suggests that long-term exposure to smaller concentrations can be harmful.

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Brain barrier opened for first time to treat cancer

Brain barrier opened for first time to treat cancer | Amazing Science |

For the first time, doctors have opened and closed the brain's protector – the blood-brain barrier – on demand. The breakthrough will allow drugs to reach diseased areas of the brain that are otherwise out of bounds. Ultimately, it could make it easier to treat conditions such as Alzheimer's and brain cancer.

The blood-brain barrier (BBB) is a sheath of cells that wraps around blood vessels (in black) throughout the brain. It protects precious brain tissue from toxins in the bloodstream, but it is a major obstacle for treating brain disorders because it also blocks the passage of drugs.

Several teams have opened the barrier in animals to sneak drugs through. Now Michael Canney at Paris-based medical start-up CarThera, and his colleagues have managed it in people using an ultrasound brain implant and an injection of microbubbles.

When ultrasound waves meet microbubbles in the blood, they make the bubbles vibrate. This pushes apart the cells of the BBB.

With surgeon Alexandre Carpentier at Pitié-Salpêtrière Hospital in Paris, Canney tested the approach in people with a recurrence of glioblastoma, the most aggressive type of brain tumour. People with this cancer have surgery to remove the tumours and then chemotherapy drugs, such as Carboplatin, are used to try to kill any remaining tumour cells. Tumours make the BBB leaky, allowing in a tiny amount of chemo drugs: if more could get through, their impact would be greater, says Canney.

The team tested the idea on four patients by implanting an ultrasound transducer through a hole already made in their skulls during tumour-removal surgery. They were then given an injection of microbubbles and had the transducer switched on for 2 minutes. This sent low-intensity pulses of ultrasound into a region of the brain just 10 millimetres by 4 mm. Canney reckons this makes the BBB in this region more permeable for about 6 hours. In this time window, each person received normal chemotherapy.

Warwick Raverty's curator insight, October 22, 2014 7:48 PM

Hope at last for people with inoperable brain tumours!

Nicole Masureik's curator insight, October 23, 2014 2:41 AM

What an amazing advance! This could open doors for all sorts of things. However, there is so much about the functioning of the brain that we don't understand, that we will need to watch the long term effects carefully.

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Bacteria Make Drug-Like Molecules in Humans: Over 14,000 biosynthetic Gene Clusters for Small Molecules Identified

Bacteria Make Drug-Like Molecules in Humans: Over 14,000 biosynthetic Gene Clusters for Small Molecules Identified | Amazing Science |

Small molecules encoded by biosynthetic gene clusters are widely used in the clinic and constitute much of the chemical language of interspecies interactions. In a recent study, researchers used a systematic approach to identify more than 3,000 small-molecule biosynthetic gene clusters in the genomes of human-associated bacteria. As reported in Cell, they discovered that biosynthetic gene clusters for thiopeptides—a class of antibiotics—are widely distributed in the genomes of the human microbiota.

“This study shows for the first time that our microbiota—the good microbes that live with humans—produce drug-like molecules to protect us from pathogens,” said lead study author Mohamed Donia of the University of California, San Francisco (UCSF). “For a long time, scientists used to go to remote and exotic places to find bacteria that produce novel chemical entities with drug-like properties. Who knew we could find similar ones in our own bodies?”

Donia and his collaborators used an algorithm they recently developed to systematically analyze about 2,400 reference genomes of the human microbiota from various body sites. They detected more than 14,000 biosynthetic gene clusters for a broad range of small-molecule classes. Reasoning that the products of these gene clusters are most likely to mediate conserved microbe-host and microbe-microbe interactions, they set out to identify the subset of gene clusters commonly found in healthy individuals by analyzing 752 metagenomic samples from the National Institutes of Health Human Microbiome Project.

Remarkably, nearly all of these gene clusters had never before been studied or even described, illustrating how little is known about their small-molecule products. “We need to study every single one of these molecules and understand what they are doing,” Donia said. “We have published the list of the small molecule-encoding genes that we identified, and we are reaching out to the scientific community to help us characterize them.”

Thiopeptides are perhaps the most interesting of these molecules because they have potent antibacterial activity against Gram-positive species. Currently, one semisynthetic member of this class is undergoing clinical trials for treating bacterial infections. But according to the authors, no thiopeptide biosynthetic gene cluster or small-molecule product from the human microbiome had ever been experimentally characterized. Surprisingly, their analysis revealed thiopeptide-like biosynthetic gene clusters in isolates from every human body site.

Donia and his collaborators went on to purify and solve the structure of a thiopeptide named lactocillin, which showed potent antibacterial activity against a range of Gram-positive vaginal pathogens. By analyzing human metatranscriptomic sequencing data, they showed that lactocillin and other thiopeptide biosynthetic gene clusters were expressed in vivo, suggesting a potential role in mediating microbe-microbe interactions.

Shang Zhuo's curator insight, October 25, 2014 9:04 AM

We can find antibiotics from our own body! It is really fascinating news. Perhaps the microbiota in our gut is a good source of bioactive molecules but is ignored by scientists for a long time.

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Geneticist George Church: A Future Without Limits

Geneticist George Church: A Future Without Limits | Amazing Science |

In the future, George Church believes, almost everything will be better because of genetics. If you have a medical problem, your doctor will be able to customize a treatment based on your specific DNA pattern. When you fill up your car, you won't be draining the world's dwindling supply of crude oil, because the fuel will come from microbes that have been genetically altered to produce biofuel. When you visit the zoo, you'll be able to take your children to the woolly mammoth or passenger pigeon exhibits, because these animals will no longer be extinct. You'll be able to do these things, that is, if the future turns out the way Church envisions it—and he's doing everything he can to see that it does.

In 2005 he launched the Personal Genome Project, with the goal of sequencing and sharing the DNA of 100,000 volunteers. With an open-source database of that size, he believes, researchers everywhere will be able to meaningfully pursue the critical task of correlating genetic patterns with physical traits, illnesses, and exposure to environmental factors to find new cures for diseases and to gain basic insights into what makes each of us the way we are. Church, tagged as subject hu43860C, was first in line for testing. Since then, more than 13,000 people in the U.S., Canada, and the U.K. have volunteered to join him, helping to establish what he playfully calls the Facebook of DNA.

Church has made a career of defying the impossible. Propelled by the dizzying speed of technological advancement since then, the Personal Genome Project is just one of Church's many attempts to overcome obstacles standing between him and the future.

"It's not for everyone," he says. "But I see a trend here. Openness has changed since many of us were young. People didn't use to talk about sexuality or cancer in polite society. This is the Facebook generation." If individuals were told which diseases or medical conditions they were genetically predisposed to, they could adjust their behavior accordingly, he reasoned. Although universal testing still isn't practical today, the cost of sequencing an individual genome has dropped dramatically in recent years, from about $7 million in 2007 to as little as $1,000 today.

"It's all too easy to dismiss the future," he says. "People confuse what's impossible today with what's impossible tomorrow.", especially through the emerging discipline of "synthetic" biology. The basic idea behind synthetic biology, he explained, was that natural organisms could be reprogrammed to do things they wouldn't normally do, things that might be useful to people. In pursuit of this, researchers had learned not only how to read the genetic code of organisms but also how to write new code and insert it into organisms. Besides making plastic, microbes altered in this way had produced carpet fibers, treated wastewater, generated electricity, manufactured jet fuel, created hemoglobin, and fabricated new drugs. But this was only the tip of the iceberg, Church wrote. The same technique could also be used on people.

"Every cell in our body, whether it's a bacterial cell or a human cell, has a genome," he says. "You can extract that genome—it's kind of like a linear tape—and you can read it by a variety of methods. Similarly, like a string of letters that you can read, you can also change it. You can write, you can edit it, and then you can put it back in the cell."

This April, the Broad Institute, where Church holds a faculty appointment, was awarded a patent for a new method of genome editing called CRISPR (clustered regularly interspersed short palindromic repeats), which Church says is one of the most effective tools ever developed for synthetic biology. By studying the way that certain bacteria defend themselves against viruses, researchers figured out how to precisely cut DNA at any location on the genome and insert new material there to alter its function. Last month, researchers at MIT announced they had used CRISPR to cure mice of a rare liver disease that also afflicts humans. At the same time, researchers at Virginia Tech said they were experimenting on plants with CRISPR to control salt tolerance, improve crop yield, and create resistance to pathogens.

The possibilities for CRISPR technology seem almost limitless, Church says. If researchers have stored a genetic sequence in a computer, they can order a robot to produce a piece of DNA from the data. That piece can then be put into a cell to change the genome. Church believes that CRISPR is so promising that last year he co-founded a genome-editing company, Editas, to develop drugs for currently incurable diseases.

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First 3D map of the cosmic web at a distance of 10.8 billion light years from Earth

First 3D map of the cosmic web at a distance of 10.8 billion light years from Earth | Amazing Science |

A team led by astronomers from the Max Planck Institute for Astronomy has created the first three-dimensional map of the 'adolescent' Universe, just 3 billion years after the Big Bang. This map, built from data collected from the W. M. Keck Observatory, is millions of light-years across and provides a tantalizing glimpse of large structures in the 'cosmic web' – the backbone of cosmic structure.

On the largest scales, matter in the Universe is arranged in a vast network of filamentary structures known as the 'cosmic web', its tangled strands spanning hundreds of millions of light-years. Dark matter, which emits no light, forms the backbone of this web, which is also suffused with primordial hydrogen gas left over from the Big Bang. Galaxies like our own Milky Way are embedded inside this web, but fill only a tiny fraction of its volume.

Now a team of astronomers led by Khee-Gan Lee, a post-doc at the Max Planck Institute for Astronomy, has created a map of hydrogen absorption revealing a three-dimensional section of the universe 11 billions light years away – the first time the cosmic web has been mapped at such a vast distance. Since observing to such immense distances is also looking back in time, the map reveals the early stages of cosmic structure formation when the Universe was only a quarter of its current age, during an era when the galaxies were undergoing a major 'growth spurt'.

The map was created by using faint background galaxies as light sources, against which gas could be seen by the characteristic absorption features of hydrogen. The wavelengths of each hydrogen feature showed the presence of gas at a specific distance from us. Combining all of the measurements across the entire field of view allowed the team a tantalizing glimpse of giant filamentary structures extending across millions of light-years, and paves the way for more extensive studies that will reveal not only the structure of the cosmic web, but also details of its function – the ways that pristine gas is funneled along the web into galaxies, providing the raw material for the formation of galaxies, stars, and planets.

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First large DNA crystals generated which could create revolutionary nanodevices

First large DNA crystals generated which could create revolutionary nanodevices | Amazing Science |

DNA has garnered attention for its potential as a programmable material platform that could spawn entire new and revolutionary nanodevices in computer science, microscopy, biology, and more. Researchers have been working to master the ability to coax DNA molecules to self assemble into the precise shapes and sizes needed in order to fully realize these nanotechnology dreams.

For the last 20 years, scientists have tried to design large DNA crystals with precisely prescribed depth and complex features — a design quest just fulfilled by a team at Harvard's Wyss Institute for Biologically Inspired Engineering. The team built 32 DNA crystals with precisely–defined depth and an assortment of sophisticated three–dimensional (3D) features, an advance reported in Nature Chemistry.

The team used their "DNA–brick self–assembly" method, which was first unveiled in a 2012 Science publication when they created more than 100 3D complex nanostructures about the size of viruses. The newly–achieved periodic crystal structures are more than 1000 times larger than those discrete DNA brick structures, sizing up closer to a speck of dust, which is actually quite large in the world of DNA nanotechnology.

"We are very pleased that our DNA brick approach has solved this challenge," said senior author and Wyss Institute Core Faculty member Peng Yin, Ph.D., who is also an Associate Professor of Systems Biology at Harvard Medical School, "and we were actually surprised by how well it works."

Scientists have struggled to crystallize complex 3D DNA nanostructures using more conventional self–assembly methods. The risk of error tends to increase with the complexity of the structural repeating units and the size of the DNA crystal to be assembled.

The DNA brick method uses short, synthetic strands of DNA that work like interlocking Lego® bricks to build complex structures. Structures are first designed using a computer model of a molecular cube, which becomes a master canvas. Each brick is added or removed independently from the 3D master canvas to arrive at the desired shape — and then the design is put into action: the DNA strands that would match up to achieve the desired structure are mixed together and self assemble to achieve the designed crystal structures.

"Therein lies the key distinguishing feature of our design strategy–its modularity," said co–lead author Yonggang Ke, Ph.D., formerly a Wyss Institute Postdoctoral Fellow and now an assistant professor at the Georgia Institute of Technology and Emory University. "The ability to simply add or remove pieces from the master canvas makes it easy to create virtually any design."

The modularity also makes it relatively easy to precisely define the crystal depth. "This is the first time anyone has demonstrated the ability to rationally design crystal depth with nanometer precision, up to 80 nm in this study," Ke said. In contrast, previous two–dimensional DNA lattices are typically single–layer structures with only 2 nm depth.

"DNA crystals are attractive for nanotechnology applications because they are comprised of repeating structural units that provide an ideal template for scalable design features", said co–lead author graduate student Luvena Ong.

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