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Genetic Scientists Eliminate Schizophrenia Symptoms in Mice by Targeting Neuregulin-1 (NRG1)

Genetic Scientists Eliminate Schizophrenia Symptoms in Mice by Targeting Neuregulin-1 (NRG1) | Amazing Science | Scoop.it

Geneticists writing in the journal Neuron reversed schizophrenia-like symptoms in adult mice by restoring normal expression to the gene Neuregulin-1 (NRG1).

 

Targeting expression of NRG1, which makes a protein important for brain development, may hold promise for treating at least some patients with the brain disorder. Like patients with schizophrenia, adult mice biogenetically-engineered to have higher NRG1 levels showed reduced activity of the brain messenger chemicals glutamate and γ-aminobutyric acid (GABA). The mice also showed behaviors related to aspects of the human illness.

“They genetically engineered mice so they could turn up levels of NRG1 to mimic high levels found in some patients then return levels to normal,” explained senior author Dr Lin Mei from the Medical College of Georgia at Georgia Regents University.

 

“They found that when elevated, mice were hyperactive, couldn’t remember what they had just learned and couldn’t ignore distracting background or white noise. When they returned NRG1levels to normal in adult mice, the schizophrenia-like symptoms went away.”

 

While schizophrenia is generally considered a developmental disease that surfaces in early adulthood, the team found that even when they kept NRG1 levels normal until adulthood, mice still exhibited schizophrenia-like symptoms once higher levels were expressed. Without intervention, they developed symptoms at about the same age humans do.

 

“This shows that high levels of NRG1 are a cause of schizophrenia, at least in mice, because when you turn them down, the behavior deficit disappears,” Dr Mei said. “Our data certainly suggests that we can treat this cause by bringing down excessive levels of NRG1 or blocking its pathologic effects.”

 

“Schizophrenia is a spectrum disorder with multiple causes – most of which are unknown – that tends to run in families, and high NRG1 levels have been found in only a minority of patients. To reduce NRG1 levels in those individuals likely would require development of small molecules that could, for example, block the gene’s signaling pathways,” Dr Mei said.

 

“Current therapies treat symptoms and generally focus on reducing the activity of two neurotransmitters since the bottom line is excessive communication between neurons.”

 

The good news is it’s relatively easy to measure NRG1 since blood levels appear to correlate well with brain levels. To genetically alter the mice, the scientists put a copy of the NRG1 gene into mouse DNA then, to make sure they could control the levels, they put in front of the DNA a binding protein for doxycycline, a stable analogue for the antibiotic tetracycline, which is infamous for staining the teeth of fetuses and babies. The mice are born expressing high levels of NRG1 and giving the antibiotic restores normal levels.

 

“If you don’t feed the mice tetracycline, the NRG1 levels are always high. Endogenous levels of the gene are not affected. High-levels of NRG1 appear to activate the kinase LIMK1, impairing release of the neurotransmitter glutamate and normal behavior. The LIMK1 connection identifies another target for intervention,” Dr Mei concluded.

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RNA Interference: Nanocoatings on bandages could deliver RNAs to shut off disease-related genes

RNA Interference: Nanocoatings on bandages could deliver RNAs to shut off disease-related genes | Amazing Science | Scoop.it

Medical researchers think specially tailored RNA sequences could turn off genes in patients’ cells to encourage wound healing or to kill tumor cells. Now researchers have developed a nanocoating for bandages that could deliver these fragile gene-silencing RNAs right where they’re needed (ACS Nano 2013, DOI:10.1021/nn401011n). The team hopes to produce a bandage that shuts down genes standing in the way of healing in chronic wounds.

 

Small interfering RNAs, or siRNAs, derail expression of specific genes in cells by binding to other RNA molecules that contain the code for those genes. Biologists have developed siRNAs that target disease-related genes. But for these siRNAs to reach the clinic, researchers must find a way to deliver the molecules safely to the right cells. Unfortunately, free oligonucleotides like siRNAs don’t fare well inside the body or cells as enzymes and acids quickly chop them up, says Paula T. Hammond, a chemical engineer at Massachusetts Institute of Technology.

 

Other groups have tackled this delivery challenge by attaching siRNAs to chemical carriers that protect the oligonucleotides as they travel through the bloodstream. The pharmaceutical company Sanofi-Aventis asked Hammond to design a vehicle that would work at the site of a wound or tumor, releasing the siRNAs over a long period of time. The company hoped that putting the biomolecules right where they’re needed, without them having to survive a trip through the bloodstream, would increase the efficacy of the treatment.

 

Hammond and her colleagues produced an siRNA-containing nanocoating that could be applied to a wide range of medical materials, such as bandages or biodegradable polymers doctors could implant during surgery to prevent an excised tumor from coming back. As the coating slowly dissolves, it releases siRNA molecules tethered to protective nanoparticles.

 

The thin films consist of two different materials: a peptide called protamine sulfate and calcium phosphate nanoparticles decorated with the therapeutic siRNAs. Other researchers have shown that similar nanoparticles help the nucleotides evade destruction once they’re taken up by cells (J. Controlled Release 2010, DOI: 10.1016/j.jconrel.2009.11.008).

 

The team alternately dips whatever they want to coat in water solutions of the two materials. The RNA and nanoparticles are negatively charged, and the peptides are positively charged. The two substances cling together due to electrostatic force, producing a film when the water dries.

 

To test their delivery method, the researchers coated woven nylon bandages with 80-nm-thick films and applied the bandages to layers of human and animal cells in culture. In one experiment, a bandage loaded with 19 µg of siRNA per square centimeter released two-thirds of its load over 10 days. Other bandages made using siRNAs targeting the gene for fluorescent green protein almost completely shut down the protein’s production in cells expressing the gene. Hammond says the group is now testing bandages that knock down MMP9, a collagen-destroying protein associated with slow healing in chronic wounds.

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DNA-guided assembly yields novel ribbon-like nanostructures

DNA-guided assembly yields novel ribbon-like nanostructures | Amazing Science | Scoop.it

Scientists at the U.S. Department of Energy's Brookhaven National Laboratory have discovered that DNA "linker" strands coax nano-sized rods to line up in way unlike any other spontaneous arrangement of rod-shaped objects. The arrangement -- with the rods forming "rungs" on ladder-like ribbons linked by multiple DNA strands -- results from the collective interactions of the flexible DNA tethers and may be unique to the nanoscale.


"This is a completely new mechanism of self-assembly that does not have direct analogs in the realm of molecular or microscale systems," said Brookhaven physicist Oleg Gang, lead author on the paper, who conducted the bulk of the research at the Lab's Center for Functional Nanomaterials.

 

Broad classes of rod-like objects, ranging from molecules to viruses, often exhibit typical liquid-crystal-like behavior, where the rods align with a directional dependence, sometimes with the aligned crystals forming two-dimensional planes over a given area. Rod shaped objects with strong directionality and attractive forces between their ends-resulting, for example, from polarized charge distribution-may also sometimes line up end-to-end forming linear one-dimensional chains.


Using synthetic DNA as a form of molecular glue to guide nanoparticle assembly has been a central approach of Gang's research at the CFN. His previous work has shown that strands of this molecule-better known for carrying the genetic code of living things-can pull nanoparticles together when strands bearing complementary sequences of nucleotide bases (known by the letters A, T, G, and C) are used as tethers, or inhibit binding when unmatched strands are used. Carefully controlling those attractive and inhibitory forces can lead to fine-tuned nanoscale engineering.

 

In the current study, the scientists used gold nanorods and single strands of DNA to explore arrangements made with complementary tethers attached to adjacent rods. They also examined the effects of using linker strands of varying lengths to serve as the tethering glue.

 

After mixing the various combinations, they studied the resulting arrangements using ultraviolet-visible spectroscopy at the CFN, and also with small-angle x-ray scattering at Brookhaven's National Synchrotron Light Source (NSLS,http://www.bnl.gov/ps/nsls/about-NSLS.asp). They also used techniques to "freeze" the action at various points during assembly and observed those static phases using scanning electron microscopy to get a better understanding of how the process progressed over time.

 

The various analysis methods confirmed the side-by-side arrangement of the nanorods arrayed like rungs on a ladder-like ribbon during the early stages of assembly, followed later by stacking of the ribbons and finally larger-scale three-dimensional aggregation due to the formation of DNA bridges between the ribbons.

 

This staged assembly process, called hierarchical, is reminiscent of self-assembly in many biological systems, for example, the linking of amino acids into chains followed by the subsequent folding of these chains to form functional proteins.

 

The stepwise nature of the assembly suggested to the team that the process could be stopped at the intermediate stages. Using "blocker" strands of DNA to bind up the remaining free tethers on the linear ribbon-like structures, they demonstrated their ability to prevent the later-stage interactions that form aggregate structures.

 

"Stopping the assembly process at the ladder-like ribbon stage could potentially be applied for the fabrication of linear structures with engineered properties," Gang said. "For example by controlling plasmonic or fluorescent properties-the materials' responses to light-we might be able to make nanoscale light concentrators or light guides, and be able to switch them on demand."


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Engineered spider protein used for anti-venom vaccine against ‘brown recluse’

Engineered spider protein used for anti-venom vaccine against ‘brown recluse’ | Amazing Science | Scoop.it
New approach to act as model for the development of non-toxic vaccines against Loxosceles spider venoms, say researchers in the journal Vaccine.

 

Researchers have engineered a spider protein that could be the start of a new generation of anti-venom vaccines with the potential to save thousands of lives worldwide. “In Brazil we see thousands of cases of people being bitten by spiders, and the bites can have very serious side-effects,” said Dr. Carlos Chávez-Olórtegui of Federal University Minas Gerais in Brazil, the corresponding author of the study.

 

“Existing anti-venoms are made of the pure toxins and can be harmful to people who take them,” he said. “We wanted to develop a new way of protecting people from the effects of Reaper spider bites, without them having to suffer from side effects.”

 

Loxosceles spiders, commonly known as reaper or recluse spiders, are found all over the world and produce harmful venoms. The toxic bite of these spiders causes skin around the bite to die and can lead to more serious effects like kidney failure and hemorrhaging. These Loxosceles spiders are most prevalent in Brazil, where they cause almost 7,000 cases of spider bites every year.

 

According to a World Health Organization report, a review of current antivenom production methods indicates that the majority of antivenoms are still produced by traditional technology using animals. The production method involves injecting the venom into animals and removing the resulting antibodies to use in the anti-venom serum for humans. These antibodies enable the human immune system to prepare to neutralize venom from bites. Although this method is somewhat effective, it is problematic as the animals required to produce the antibodies do suffer from the effects of the venom.In an attempt to improve these conditions Dr. Chávez-Olortegui and his team of researchers identified a protein that can be engineered in the lab, omitting the need to use real spider venom. It is made up of three proteins rather than the whole venom toxin, so it is not harmful to the immunized animal that produces the antibodies for use in the human serum. It is also more effective than existing approaches and easier to produce than preparing crude venom from spiders.

 

The researchers tested the lab-engineered protein on rabbits and showed an immune response similar to the way they respond to the whole toxin, previously experienced in the old method. The protein was effective for venom of two sub-species of Loxosceles spiders, which have similar toxins. The rabbits were protected from skin damage at the site of the venom injection and from hemorrhaging.

 

The authors concluded that this engineered protein may be a promising candidate for vaccination against Loxosceles spider bites in the future.

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Bioteeth From Stemcells Will Regrow Complete Tooth, Superior to Implants

Bioteeth From Stemcells Will Regrow Complete Tooth, Superior to Implants | Amazing Science | Scoop.it

Replacing missing teeth with new bioengineered teeth, grown from stem cells generated from a person's own gum cells, is a new method that will be vastly superior to the currently used implant technology.

 

New research, published in the Journal of Dental Research and led by Professor Paul Sharpe, an expert in craniofacial development and stem cell biology at King's College London's Dental Institute, describes advances in the development of this method by sourcing the required cells from a patient's own gum.

 

Research towards producing bioengineered teeth, also called bioteeth, aims to grow new and natural teeth by employing stem cell technology which generates immature teeth (teeth primordia) that mimic those in the embryo. These can be transplanted as small cell pellets into the adult jaw to develop into functional teeth, the researchers say.

 

Remarkably, despite the very different environments, embryonic teeth primordia can develop normally in the adult mouth. Embryonic tooth primordia cells can readily form immature teeth following dissociation into single cell populations and subsequent recombination, but such cell sources are impractical to use in a general therapy.

 

"What is required is the identification of adult sources of human epithelialand mesenchymal [stem] cells that can be obtained in sufficient numbers to make biotooth formation a viable alternative to dental implants," said Sharpe.

 

This challenge was now solved by the researchers, who sucessfully isolated adult human gum (gingival) tissue from patients at the Dental Institute at King's College London, grew more of it in the lab, and then combined it with the cells of mice that form teeth (mesenchyme cells). By transplanting this combination of cells into mice, the researchers were able to grow hybrid human/mouse teeth containing dentine and enamel, as well as viable roots.

 

"Epithelial cells derived from adult human gum tissue are capable of responding to tooth inducing signals from embryonic tooth mesenchyme in an appropriate way to contribute to tooth crown and root formation and give rise to relevant differentiated cell types, following in vitro culture," said Sharpe.

 

"These easily accessible epithelial cells are thus a realistic source for consideration in human biotooth formation. The next major challenge is to identify a way to culture adult human mesenchymal cells to be tooth-inducing, as at the moment we can only make embryonic mesenchymal cells do this."

 

Current implant-based methods of whole tooth replacement fail to reproduce a natural root structure and as a consequence of the friction from eating and other jaw movement, loss of jaw bone can occur around the implant.

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Jennifer Frezza 's curator insight, December 8, 2013 6:28 PM

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Scientists have crossed two strains of avian flu virus to create one that can be transmitted through the air

Scientists have crossed two strains of avian flu virus to create one that can be transmitted through the air | Amazing Science | Scoop.it

As the world is transfixed by a new H7N9 bird flu virus spreading through China, a study reminds us that a different avian influenza — H5N1 — still poses a pandemic threat.

 

A team of scientists in China has created hybrid viruses by mixing genes from H5N1 and the H1N1 strain behind the 2009 swine flu pandemic, and showed that some of the hybrids can spread through the air between guinea pigs.

 

Flu hybrids can arise naturally when two viral strains infect the same cell and exchange genes. This process, known as reassortment, produced the strains responsible for at least three past flu pandemics, including the one in 2009.

 

There is no evidence that H5N1 and H1N1 have reassorted naturally yet, but they have many opportunities to do so. The viruses overlap both in their geographical range and in the species they infect, and although H5N1 tends mostly to swap genes in its own lineage, the pandemic H1N1 strain seems to be particularly prone to reassortment.

 

“If these mammalian-transmissible H5N1 viruses are generated in nature, a pandemic will be highly likely,” says Hualan Chen, a virologist at the Harbin Veterinary Research Institute of the Chinese Academy of Sciences, who led the study.

 

“It's remarkable work and clearly shows how the continued circulation of H5N1 strains in Asia and Egypt continues to pose a very real threat for human and animal health,” says Jeremy Farrar, director of the Oxford University Clinical Research Unit in Ho Chi Minh City, Vietnam.

 

Chen's results are likely to reignite the controversy that plagued the flu community last year, when two groups found that H5N1 could go airborne if it carried certain mutations in a gene that produced a protein called haemagglutinin (HA). Following heated debate over biosecurity issues raised by the work, the flu community instigated a voluntary year-long moratorium on research that would produce further transmissible strains. Chen’s experiments were all finished before the hiatus came into effect, but more work of this nature can be expected now that the moratorium has been lifted.

 

“I do believe such research is critical to our understanding of influenza,” says Farrar. “But such work, anywhere in the world, needs to be tightly regulated and conducted in the most secure facilities, which are registered and certified to a common international standard.”

 

Virologists have created H5N1 reassortants before. One study found that H5N1 did not produce transmissible hybrids when it reassorts with a flu strain called H3N2. But in 2011, Stacey Schultz-Cherry, a virologist at St. Jude Children's Research Hospital in Memphis, Tennessee, showed that pandemic H1N1 becomes more virulent if it carries the HA gene from H5N1.

 

Chen’s team mixed and matched seven gene segments from H5N1 and H1N1 in every possible combination, to create 127 reassortant viruses, all with H5N1’s HA gene. Some of these hybrids could spread through the air between guinea pigs in adjacent cages, as long as they carried either or both of two genes from H1N1 called PA and NS. Two further genes from H1N1, NA and M, promoted airborne transmission to a lesser extent, and another, the NP gene, did so in combination with PA.

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WIRED: Bioengineers Build Open Source Language for Programming Cells

WIRED: Bioengineers Build Open Source Language for Programming Cells | Amazing Science | Scoop.it

Drew Endy wants to build a programming language for the body.

Endy is the co-director of the International Open Facility Advancing Biotechnology — BIOFAB, for short — where he’s part of a team that’s developing a language that will use genetic data to actually program biological cells. That may seem like the stuff of science fiction, but the project is already underway, and the team intends to open source the language, so that other scientists can use it and modify it and perfect it.

 

The effort is part of a sweeping movement to grab hold of our genetic data and directly improve the way our bodies behave — a process known as bioengineering. With the Supreme Court exploring whether genes can be patented, the bioengineering world is at crossroads, but scientists like Endy continue to push this technology forward.

 

Genes contain information that defines the way our cells function, and some parts of the genome express themselves in much the same way across different types of cells and organisms. This would allow Endy and his team to build a language scientists could use to carefully engineer gene expression – what they call “the layer between the genome and all the dynamic processes of life.”

 

The BIOFAB project is still in the early stages. Endy and the team are creating the most basic of building blocks — the “grammar” for the language. Their latest achievement, recently reported in the journalScience, has been to create a way of controlling and amplifying the signals sent from the genome to the cell. Endy compares this process to an old fashioned telegraph.

 

“If you want to send a telegraph from San Francisco to Los Angeles, the signals would get degraded along the wire,” he says. “At some point, you have to have a relay system that would detect the signals before they completely went to noise and then amplify them back up to keep sending them along their way.”

 

And, yes, the idea is to build a system that works across different types of cells. In the 90s, the computing world sought to create a common programming platform for building applications across disparate systems — a platform called the Java virtual machine. Endy hopes to duplicate the Java VM in the biological world.

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Cancer cells, stem cells and muscle cells may owe their unique identities to powerful gene-regulating structures called super-enhancers

Cancer cells, stem cells and muscle cells may owe their unique identities to powerful gene-regulating structures called super-enhancers | Amazing Science | Scoop.it
Long chunks of DNA improve efficiency of gene activators.

 

Different cell types in the body contain the same genetic information but have different genes activated. Short stretches of DNA in the genome called enhancers act like switches for these genes, flipping them 'on' when certain proteins attach to them. Two studies published in Cell now show that enhancers become even more powerful when many of them join together. Richard Young, a cancer researcher at the Whitehead Institute in Cambridge, Massachusetts, and senior author of both papers, has dubbed these giant groupings super-enhancers.

 

In the study led by Jakob Lovén at the Whitehead Institute the team looked at cancer cells that owe their out-of-control growth to a notorious gene named MYC. They found that super-enhancers had formed within the cells near the MYC gene, and that the structures catalysed high production of MYC protein. They also found that the super-enhancers could easily be perturbed, causing MYC protein levels to plummet. The Whitehead Institute's Warren Whyte and his colleagues then went on to show that ordinary, healthy cells also seem to depend on super-enhancers.

 

Young says that the fragility of the super-enhancers means that scientists may have a fruitful new way to study cancers. Rather than designing drugs that block MYC — a technique that has thus far been unsuccessful — he suggests that investigators try to hinder the super-enhancer complex that brings MYC to power. Young’s teams discovered super-enhancers while pursuing a conundrum. Back in 2011, scientists had reported that blocking a protein called Brd4 in mice with leukaemia would cause the amounts of Myc protein in cancer cells to diminish sharply and stop the cancer cells from proliferating. But Brd4 is known to help activate enhancers in both healthy and cancerous cells, so how could the Brd4 inhibitors be leaving normal cells unscathed? “I thought, maybe BRD4 does something special to MYC that it does not do to other genes,” says Young.

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Three-dimensional graphene foam as a biocompatible and conductive scaffold for neural stem cells

Three-dimensional graphene foam as a biocompatible and conductive scaffold for neural stem cells | Amazing Science | Scoop.it

Neural stem cell (NSC) based therapy provides a promising approach for neural regeneration. For the success of NSC clinical application, a scaffold is required to provide three-dimensional (3D) cell growth microenvironments and appropriate synergistic cell guidance cues. A team of scientists reports now the first utilization of graphene foam, a 3D porous structure, as a novel scaffold for NSCs in vitro. It was found that three-dimensional graphene foams (3D-GFs) can not only support NSC growth, but also keep cell at an active proliferation state with upregulation of Ki67 expression than that of two-dimensional graphene films. Meanwhile, phenotypic analysis indicated that 3D-GFs can enhance the NSC differentiation towards astrocytes and especially neurons. Furthermore, a good electrical coupling of 3D-GFs with differentiated NSCs for efficient electrical stimulation was observed. These findings implicate 3D-GFs could offer a powerful platform for NSC research, neural tissue engineering and neural prostheses.

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Three-dimensional #graphene foam as a biocompatible and conductive scaffold for neural stem cells

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Nanoscribe: 3D Scaffolds for Biomimetics for Cell Biology

Nanoscribe: 3D Scaffolds for Biomimetics for Cell Biology | Amazing Science | Scoop.it

3D polymer scaffolds for cells: Biocompatible 3D microstructures act as artificial extracellular matrices for cells to mimic a natural but reproducible environment. Other applications are the fabrication of micro-needles, stents and so on for medical purposes.

 

Shown are a series of structures fabricated by means of the direct laser writing technique with Photonic Professional systems. Typical topics of interest which are under investigation are the study of cell migration or stem cell differentiation. The 3D tailored environment acts as an artificial extracellular matrix, i.e., a scaffold for the cells. Pictures: F. Klein, B. Richter J. Fischer, T. Striebel und M. Bastmeyer; Karlsruher Institut für Technologie (KIT). 

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Biological transistor (transcriptor) enables computing within living cells

Biological transistor (transcriptor) enables computing within living cells | Amazing Science | Scoop.it

ENIAC, the first modern computer developed in the 1940s, used vacuum tubes and electricity. Today, computers use transistors made from highly engineered semiconducting materials to carry out their logical operations. And now a team of Stanford University bioengineers has taken computing beyond mechanics and electronics into the living realm of biology. In a paper to be published March 28 in Science, the team details a biological transistor made from genetic material — DNA and RNA — in place of gears or electrons. The team calls its biological transistor the “transcriptor.”

 

“Transcriptors are the key component behind amplifying genetic logic — akin to the transistor and electronics,” said Jerome Bonnet, PhD, a postdoctoral scholar in bioengineering and the paper’s lead author. The creation of the transcriptor allows engineers to compute inside living cells to record, for instance, when cells have been exposed to certain external stimuli or environmental factors, or even to turn on and off cell reproduction as needed. “Biological computers can be used to study and reprogram living systems, monitor environments and improve cellular therapeutics,” said Drew Endy, PhD, assistant professor of bioengineering and the paper’s senior author.

In electronics, a transistor controls the flow of electrons along a circuit. Similarly, in biologics, a transcriptor controls the flow of a specific protein, RNA polymerase, as it travels along a strand of DNA.

 

“We have repurposed a group of natural proteins, called integrases, to realize digital control over the flow of RNA polymerase along DNA, which in turn allowed us to engineer amplifying genetic logic,” said Endy. Using transcriptors, the team has created what are known in electrical engineering as logic gates that can derive true-false answers to virtually any biochemical question that might be posed within a cell. They refer to their transcriptor-based logic gates as “Boolean Integrase Logic,” or “BIL gates” for short. Transcriptor-based gates alone do not constitute a computer, but they are the third and final component of a biological computer that could operate within individual living cells.

 

Despite their outward differences, all modern computers, from ENIAC to Apple, share three basic functions: storing, transmitting and performing logical operations on information.

 

Last year, Endy and his team made news in delivering the other two core components of a fully functional genetic computer. The first was a type of rewritable digital data storage within DNA. They also developed a mechanism for transmitting genetic information from cell to cell, a sort of biological Internet.

 

“The potential applications are limited only by the imagination of the researcher,” said co-author Monica Ortiz, a PhD candidate in bioengineering who demonstrated autonomous cell-to-cell communication of DNA encoding various BIL gates.

 

To create transcriptors and logic gates, the team used carefully calibrated combinations of enzymes — the integrases mentioned earlier — that control the flow of RNA polymerase along strands of DNA. If this were electronics, DNA is the wire and RNA polymerase is the electron.

 

“The choice of enzymes is important,” Bonnet said. “We have been careful to select enzymes that function in bacteria, fungi, plants and animals, so that bio-computers can be engineered within a variety of organisms.”

 

On the technical side, the transcriptor achieves a key similarity between the biological transistor and its semiconducting cousin: signal amplification. 

With transcriptors, a very small change in the expression of an integrase can create a very large change in the expression of any two other genes.

 

To understand the importance of amplification, consider that the transistor was first conceived as a way to replace expensive, inefficient and unreliable vacuum tubes in the amplification of telephone signals for transcontinental phone calls. Electrical signals traveling along wires get weaker the farther they travel, but if you put an amplifier every so often along the way, you can relay the signal across a great distance. The same would hold in biological systems as signals get transmitted among a group of cells.

 

“It is a concept similar to transistor radios,” said Pakpoom Subsoontorn, a PhD candidate in bioengineering and co-author of the study who developed theoretical models to predict the behavior of BIL gates. “Relatively weak radio waves traveling through the air can get amplified into sound.”

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Origami sphere: DNA folding takes a fresh direction

Origami sphere: DNA folding takes a fresh direction | Amazing Science | Scoop.it

The intricate art of DNA origami has been given a fresh twist. Researchers at Arizona State University in Tempe have managed to coerce a single strand of DNA to fold back on itself to form an array of two- and three-dimensional nanostructures.

 

DNA origami involves using scaffolding to guide a single strand of DNA as it folds up to form a shape. The Arizona team, led by Hao Yan, managed to create more intricate shapes than have been possible so far, by using scaffolding made up of cross-like structures of two DNA strands nearly at right angles to each other.

 

Similar cross-shaped structures, called Holliday junctions, are not new. But it had been thought impossible to link them together to make a stable scaffold because the charge of the DNA molecules was always mismatched.

 

Yan and his team overcame this problem by tweaking the way they assembled their scaffold so that the junctions became slightly ‘twisted’. The result was that junctions could link together to form a waffle-like gridiron structure that is “surprisingly very stable”, Yan says.

Using this, the team was able to guide the formation of not only two-dimensional DNA structures but also three-dimensional spheres and screw-like shapes. The scaffold and the various structures it can produce are published in Science today.

 

Yan hopes that DNA origami can now become more useful, perhaps building three-dimensional ‘cages’ to hold drugs and so deliver them to the specific place they are needed in the body.

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De-Extinction: Can Cloning Bring Extinct Species Back to Life?

De-Extinction: Can Cloning Bring Extinct Species Back to Life? | Amazing Science | Scoop.it

At some point in the next decade, if advances in biotechnology continue on their current path, clones of extinct species such as the passenger pigeon, Tasmanian tiger and wooly mammoth could once again live among us. But cloning lost species—or “de-extinction” as some scientists call it—presents us with myriad ethical, legal and regulatory questions that must be answered, such as which (if any) species should be brought back and whether or not such creatures could be allowed to return to the wild. Such questions are set to be addressed at the TEDx DeExtinction conference, a day-long event in Washington, D.C., organized by Stewart Brand’s Revive & Restore project. Brand previewed the topics for discussion last week at the TED2013 conference in Long Beach, Calif.

 

Scientists are actively working on methods and procedures for bringing extinct species back to life, says Ryan Phelan, executive director of Revive & Restore and co-organizer of the TEDx event. “The technology is moving fast. What Stewart and I are trying to do with this meeting is for the first time to allow the public to start thinking about this. We’re going to hear from people who take it quite seriously. De-extinction is going to happen, and the questions are how does it get applied, when does it get used, what are the criteria which are going to be set?”

 

Cloning extinct species has been tried before—with moderate success. An extinct Pyrenean ibex, or bucardo, (Capra pyrenaica pyrenaica) was born to a surrogate mother goat in 2009, nine years after the last member of its species was killed by a falling tree. The cloned animal lived for just seven minutes. Revive & Restore itself has launched a project to try to resurrect the passenger pigeon, which went extinct in 1914.

 

More: http://www.wired.com/wiredscience/2013/03/passenger-pigeon-de-extinction/

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Peter Phillips's curator insight, March 15, 2013 4:28 PM

The release of the Monash University team's progress emplanting DNA from an extinct gastric brooder frog is an example of this... and also of how competetive research is... they decided to publish in a newspaper... traditionally a shortcut to fame when many people are about to discover the same thing. Good luck to all however, who work to maintain and reinstate the diversity of life on our planet, and congratulations for the dogged detective work!

Eduardo Carriazo's curator insight, May 15, 2014 9:14 AM

I chose this article because it has good information and if I was someone studying this I would use this source. I also choose this article because it changed my mind about de - extinction. If you can do it, you should do it.

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Russian scientists find frozen blood in mammoth carcass, boosting their chances of cloning

Russian scientists find frozen blood in mammoth carcass, boosting their chances of cloning | Amazing Science | Scoop.it

Russian scientists claimed Wednesday they have discovered blood in the carcass of a woolly mammoth, adding that the rare find could boost their chances of cloning the prehistoric animal. An expedition led by Russian scientists earlier this month uncovered the well-preserved carcass of a female mammoth on a remote island in the Arctic Ocean.

 

Semyon Grigoryev, the head of the expedition, said the animal died at the age of around 60 some 10,000 to 15,000 years ago, and that it was the first time that an old female had been found.

 

But what was more surprising was that the carcass was so well preserved that it still had blood and muscle tissue. "When we broke the ice beneath her stomach, the blood flowed out from there, it was very dark," Grigoryev, who is a scientist at the Yakutsk-based Northeastern Federal University, told AFP.

 

"This is the most astonishing case in my entire life. How was it possible for it to remain in liquid form? And the muscle tissue is also red, the colour of fresh meat," he added. Grigoryev said that the lower part of the carcass was very well preserved as it ended up in a pool of water that later froze over. The upper part of the body including the back and the head are believed to have been eaten by predators, he added.

 

"The forelegs and the stomach are well preserved, while the hind part has become a skeleton." The discovery, Grigoryev said, gives new hope to researchers in their quest to bring the woolly mammoth back to life.

 

"This find gives us a really good chance of finding live cells which can help us implement this project to clone a mammoth," he said. "Previous mammoths just have not had such well-preserved tissue."

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Ahmed Atef's comment, May 31, 2013 5:47 AM
i can do this cloning ;)
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41 of 43 patients with HIV stay healthy for over 11 years after initial gene therapy, T-cells perpetuate & persist

41 of 43 patients with HIV stay healthy for over 11 years after initial gene therapy, T-cells perpetuate & persist | Amazing Science | Scoop.it

HIV patients treated with genetically modified T cells remain healthy up to 11 years after initial therapy, researchers from the Perelman School of Medicine at the University of Pennsylvania report in the new issue of Science Translational Medicine. The results provide a framework for the use of this type of gene therapy as a powerful weapon in the treatment of HIV, cancer, and a wide variety of other diseases.

 

"We have 43 patients and they are all healthy," says senior author Carl June, MD, a professor of Pathology and Laboratory Medicine at Penn Medicine. "And out of those, 41 patients show long term persistence of the modified T cells in their bodies."

 

Early gene therapy studies raised concern that gene transfer to cells via retroviruses might lead to leukemia in a substantial proportion of patients, due to mutations that may arise in genes when new DNA is inserted. The new long-term data, however, allay that concern in T cells, further buoying the hope generated by work June's team published in 2011 showing the eradication of tumors in patients with chronic lymphocytic leukemia using a similar strategy.

 

"If you have a safe way to modify cells in patients with HIV, you can potentially develop curative approaches," June says. "Patients now have to take medicine for their whole lives to keep their virus under control, but there are a number of gene therapy approaches that might be curative." A lifetime of anti-HIV drug therapy, by contrast, is expensive and can be accompanied by significant side effects.

 

They also note that the approach the Penn Medicine team studied may allow patients with cancers and other diseases to avoid the complications and mortality risks associated with more conventional treatments, since patients treated with the modified T cells did not require drugs to weaken their own immune systems in order for the modified cells to proliferate in their bodies after infusion, as is customary for cancer patients who receive stem cell transplants.

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Human stem cells cloned for the first time

Human stem cells cloned for the first time | Amazing Science | Scoop.it

An international team of scientists announced today that for the first time ever, they were able to create new human stem cells by cloning older, fully mature human cells. The process cannot be used to create full human clones, as the scientists involved were quick to point out, but it does allow for cells to be grown to fit specific functions within an individual's body — resulting in new, patient-specific liver cells or heart cells that actually pulse on their own, for example.

 

Eventually, scientists hope to refine the process to the point it could be used to help treat disease and even create whole custom organs, but that is likely to be several years away at the earliest. "While there is much work to be done in developing safe and effective stem cell treatments, we believe this is a significant step forward in developing the cells that could be used in regenerative medicine," said Shoukhrat Mitalipov, the leader of the research team and a senior scientist at the Oregon National Primate Research Center (ONPRC), in a news release.

 

The research team was led by scientists at the Oregon Health & Science University, who used a technique similar to the one that created Dolly the sheep, the first mammal cloned from adult cells, back in 1996. In a basic sense, this method involves taking an adult cell from a patient's body, sucking out the central portion containing DNA (the nucleus), then injecting this material into an empty egg cell donated by another human volunteer. The genetic material from the adult cell tells the empty egg cell what type it should mature into.

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Privacy protections needed? The genome hacker shows how individuals can be identified from 'anonymous' DNA

Privacy protections needed? The genome hacker shows how individuals can be identified from 'anonymous' DNA | Amazing Science | Scoop.it

Late at night, a video camera captures a man striding up to the locked door of the information-technology department of a major Israeli bank. At this hour, access can be granted only by a fingerprint reader — but instead of using the machine, the man pushes a button on the intercom to ring the receptionist's phone. As it rings, he holds his mobile phone up to the intercom and presses the number 8. The sound of the keypad tone is enough to unlock the door. As he opens it, the man looks back to the camera with a shrug: that was easy.

 

Yaniv Erlich — the star of this 2006 video — considers this one of his favourite hacks. Technically a “penetration exercise” conducted to expose the bank's vulnerabilities, it was one of several projects that Erlich worked on during a two-year stint with a security firm based near Tel Aviv. Since then, the 33-year-old computational biologist has been bringing his hacker ethos to biology. Now at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, he is using genome data in new ways, and in the process exposing vulnerabilities in databases that hold sensitive information on thousands of individuals around the world.

 

In a study published in January, Erlich's lab showed that it is possible to discover the identities of people who participate in genetic research studies by cross-referencing their data with publicly available information. Previous studies had shown that people listed in anonymous genetic data stores could be unmasked by matching their data to a sample of their DNA. But Erlich showed that all it requires is an Internet connection.

 

Erlich's work has exposed a pressing ethical quandary. As researchers increasingly combine patient data with other types of information — everything from social-media posts to entries on genealogy websites — protecting anonymity becomes next to impossible. Studying these linked data has its benefits, but it may also reveal genetic and medical information that researchers had promised to keep private — and that, if made public, might hurt people's employability, insurability or even personal relationships.

 

Such revelations may make the scientific community uncomfortable and undermine the public's trust in medical research. But Erlich and his colleagues see their work as a way to alert the world about flawed systems, keep researchers honest and ultimately strengthen science. In March, for instance, the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, claimed that the genome sequence that it had published for the HeLa cell line would not reveal anything about Henrietta Lacks — the source of the cells — or her descendants. Erlich issued a tart response: “Nice lie EMBL!” he tweeted. The sequence was later pulled from public databases, and the EMBL admitted that it would indeed be possible to glean information about the Lacks family from it, even though much of the HeLa genetic data had already been published as part of other studies.

 

“Most scientists would not go anywhere close to these questions, out of a sense of what it might mean for the field, or for them personally,” says David Page, director of the Whitehead Institute, who has advised Erlich about his research. “But this is not about publicity-seeking — this is about fearlessness, and a kind of interest in how all the parts of the Universe fit together that mark all of Yaniv's work.”

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Muscles in old mice made young again

Muscles in old mice made young again | Amazing Science | Scoop.it

Researchers have identified for the first time a key factor responsible for declining muscle repair during aging, and discovered that a common drug halts the process in mice.

 

A dormant reservoir of stem cells is present inside every muscle, ready to be activated by exercise and injury to repair any damage. When needed, these cells divide into hundreds of new muscle fibers that repair the muscle. At the end of the repairing process some of the cells also replenish the pool of dormant stem cells so that the muscle retains the ability to repair itself again and again.

 

The researchers carried out a study on old mice and found the number of dormant stem cells present in the pool reduces with age, which could explain the decline in the muscle’s ability to repair and regenerate as it gets older.

When these old muscles were screened the team found high levels of FGF2, a protein that has the ability to stimulate cells to divide. While encouraging stem cells to divide and repair muscle is a normal and crucial process, they found that FGF2 could also awaken the dormant pool of stem cells even when they were not needed. The continued activation of dormant stem cells meant the pool was depleted over time, so when the muscle really needed stem cells to repair itself the muscle was unable to respond properly.

 

Researchers then attempted to inhibit FGF2 in old muscles to prevent the stem cell pool from being kick-started into action unnecessarily. By administering a common FGF2 inhibitor drug they were able to inhibit the decline in the number of muscle stem cells in the mice.

 

“Preventing or reversing muscle wasting in old age in humans is still a way off, but this study has for the first time revealed a process which could be responsible for age-related muscle wasting, which is extremely exciting,” says Albert Basson, Senior Lecturer from the department of craniofacial development and stem cell biology at the King’s College London Dental Institute.

 

“The finding opens up the possibility that one day we could develop treatments to make old muscles young again. If we could do this, we may be able to enable people to live more mobile, independent lives as they age.”

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Escherichia coli bacteria produce diesel on demand

Escherichia coli bacteria produce diesel on demand | Amazing Science | Scoop.it

A team from the University of Exeter, with support from Shell, has developed a method to make bacteria produce diesel on demand. While the technology still faces many significant commercialisation challenges, the diesel, produced by special strains of E. coli bacteria, is almost identical to conventional diesel fuel and so does not need to be blended with petroleum products as is often required by biodiesels derived from plant oils. This also means that the diesel can be used with current supplies in existing infrastructure because engines, pipelines and tankers do not need to be modified. Biofuels with these characteristics are being termed 'drop-ins'.

Professor John Love from Biosciences at the University of Exeter said: "Producing a commercial biofuel that can be used without needing to modify vehicles has been the goal of this project from the outset. Replacing conventional diesel with a carbon neutral biofuel in commercial volumes would be a tremendous step towards meeting our target of an 80% reduction in greenhouse gas emissions by 2050. Global demand for energy is rising and a fuel that is independent of both global oil price fluctuations and political instability is an increasingly attractive prospect."

 

E. coli bacteria naturally turn sugars into fat to build their cell membranes. Synthetic fuel oil molecules can be created by harnessing this natural oil production process. Large scale manufacturing using E. coli as the catalyst is already commonplace in the pharmaceutical industry and, although the biodiesel is currently produced in tiny quantities in the laboratory, work will continue to see if this may be a viable commercial pathway to 'drop in' fuels.


Rob Lee from Shell Projects & Technology said: "We are proud of the work being done by Exeter in using advanced biotechnologies to create the specific hydrocarbon molecules that we know will continue to be in high demand in the future. While the technology still faces several hurdles to commercialisation, by exploring this new method of creating biofuel, along with other intelligent technologies, we hope they could help us to meet the challenges of limiting the rise in carbon dioxide emissions while responding to the growing global requirement for transport fuel."

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Nanoparticle disguised as blood cell fights bacterial infections

Nanoparticle disguised as blood cell fights bacterial infections | Amazing Science | Scoop.it

A nanoparticle wrapped in a red blood cell membrane can remove toxins from the body and could be used to fight bacterial infections, according to research published today in Nature Nanotechnology.

 

The results demonstrate that the nanoparticles could be used to neutralize toxins produced by many bacteria, including some that are antibiotic-resistant, and could counteract the toxicity of venom from a snake or scorpion attack, says Liangfang Zhang, a professor of nanoengineering at the University of California, San Diego. Zhang led the research.

 

The “nanosponges” work by targeting so-called pore-forming toxins, which kill cells by poking holes in them. One of the most common classes of protein toxins in nature, pore-forming toxins are secreted by many types of bacteria, includingStaphylococcus aureus, of which antibiotic-resistant strains, called MRSA, are endemic in hospitals worldwide and cause tens of thousands of deaths annually. They are also present in many types of animal venom.

 

There are a range of existing therapies designed to target the molecular structure of pore-forming toxins and disable their cell-killing functions. But they must be customized for different diseases and conditions, and there are over 80 families of these harmful proteins, each with a different structure. Using the new nanosponge therapy, says Zhang, “we can neutralize every single one, regardless of their molecular structure.”

 

Zhang and his colleagues wrapped real red blood cell membranes around biocompatible polymeric nanoparticles. A single red blood cell supplies enough membrane material to produce over 3,000 nanosponges, each around 85 nanometers (a nanometer is a billionth of a meter) in diameter. Since red blood cells are a primary target of pore-forming toxins, the nanosponges act as decoys once in the bloodstream, absorbing the damaging proteins and neutralizing their toxicity. And because they are so small, the nanosponges will vastly outnumber the real red blood cells in the system, says Zhang. This means they have a much higher chance of interacting with and absorbing toxins, and thus can divert the toxins away from their natural targets.

 

In animal tests, the researchers showed that the new therapy greatly increased the survival rate of mice given a lethal dose of one of the most potent pore-forming toxins. Liver biopsies several days following the injection revealed no damage, indicating that the nanosponges, along with the sequestered toxins, were safely digested after accumulating in the liver.

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MIT and Harvard engineers create graphene electronics with DNA-based lithography

MIT and Harvard engineers create graphene electronics with DNA-based lithography | Amazing Science | Scoop.it

Chemical and molecular engineers at at MIT and Harvard have successfully used templates made of DNA to cheaply and easily pattern graphene into nanoscale structures that could eventually be fashioned into electronic circuits.

 

Graphene, as you are surely aware by now, is a material with almost magical properties. It is the strongest and most electrically conductive material known to humankind. Semiconductor masters, such as Intel and TSMC, would absolutely love to use graphene to fashion computer chips are capable of operating at hundreds of gigahertz while consuming tiny amounts of power. Unfortunately, though, graphene is much more difficult and expensive to work with than silicon — and, in its base state, it isn’t a semiconductor. The DNA patterning performed by MIT and Harvard seeks to rectify both of these issues, by making graphene easy to work with, and thus easy to turn it into a semiconductor for use in computer chips.

 

Late last year, Harvard’s Wyss Institute announced that it had discovered a technique forbuilding intricately detailed DNA nanostructures out of DNA “Lego bricks.” These bricks are specially crafted strands of DNA that join together with other DNA bricks at a 90-degree angle. By joining enough of these bricks together, a three-dimensional 25-nanometer cube emerges. By altering which DNA bricks are available during this process, the Wyss Institute was capable of forming 102 distinct 3D shapes, as seen in the image and video below.

 

The MIT and Harvard researchers are essentially taking these shapes and binding them to a graphene surface with a molecule called aminopyrine. Once bound, the DNA is coated with a layer of silver, and then a layer of gold to stabilize it. The gold-covered DNA is then used as a mask for plasma lithography, where oxygen plasma burns away the graphene that isn’t covered. Finally, the DNA mask is washed away with sodium cyanide, leaving a piece of graphene that is an almost-perfect copy of the DNA template.

 

So far, the researchers have used this process — dubbed metallized DNA nanolithography— to create X and Y junctions, rings, and ribbons out of graphene. Nanoribbons, which are simply very narrow strips of graphene, are of particular interest because they have a bandgap — a feature that graphene doesn’t normally possess. A bandgap means that these nanoribbons have semiconductive properties, which means they might one day be used in computer chips. Graphene rings are also of interest, because they can be fashioned into quantum interference transistors — a new and not-well-understood transistor that connects three terminals to a ring, with the transistor’s gate being controlled by the flow of electrons around the ring.

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Quality control opens path to synthetic biology's Ikea - Next industrial revolution could be biological

Quality control opens path to synthetic biology's Ikea - Next industrial revolution could be biological | Amazing Science | Scoop.it

Think living machines that produce energy from landfill waste, biological sensors that detect dirty water or bacterial production lines that churn out drugs.

 

These are just some of the applications that synthetic biology – applying engineering principles to biological parts – could make possible. That goal is looking more likely now that, for the first time, researchers have established a set of rules that could allow parts to be assembled with industrial rigour. Libraries of these standardised high-quality parts will let engineers pick components knowing how they will behave.

 

The behaviour of all living matter is governed by gene expression, the process by which biological materials such as proteins are made. So synthetic biology's "parts" are the DNA sequences that contain certain manufacturing instructions. When these parts are stuck together, the genes are expressed and the required protein is made.

 

Researchers have been building one-off biological machines by combining several of these parts for years. But, because there is little quality control, producing them on an industrial scale has so far been impossible. To change this, Drew Endy, co-director of the BIOFAB facility in California, and his colleagues have developed a mathematical framework to show how each part interacts with others and whether this results in the right amount of the right product being made. The work involved physically testing out hundreds of combinations of common biological components and using the results to create a scoring system, effectively establishing a standard of excellence that should let engineers build their most reliable devices yet (Nucleic Acids Research, doi.org/kw7).

 

The team found that bundling parts together according to their specific function gave more reliable results than considering them separately. This is how nature does it, says Endy, but the dogma had been that all parts should be clearly separated and assembled in a more modular way, which was the principle used to set up the BioBricks registry, an existing library of parts, in 2003. It was a case of "let's change our religion on how you assemble things", says Endy.

 

This realisation enabled the team to design hundreds of combinations of DNA segments from the Escherichia coli genome – one of the most commonly used source of parts – to build up a library of parts with a reliability of around 93 per cent.

 

"It's really great to have honest metrics for the performance of parts," saysChristopher Voigt at the Massachusetts Institute of Technology, who four years ago developed components that worked about 50 per cent of the time. It should help remove the element of trial and error that synthetic biologists have so far had to live with. "It's normally done in an ad-hoc way," says Voigt. "You just drop in the part and hope you get what you want."

 

For the BIOFAB group, whose aim is to mass-produce their standardised parts and ship them to researchers around the world, this is just the start. The scoring system should apply to a wide range of organisms and there are many more families of parts that need to be catalogued, such as those from other commonly used bacteria like salmonella and Rhodobacter. "It's a slow, hard slog but it's essential," says Voigt.

 

One thing is for sure: biology is undergoing developments that parallel the industrial revolution, says Richard Kitney at Imperial College London. Only recently, for example, it might have taken 10 bioengineers more than 10 years to build something that produced a single drug. This is akin to the cottage industries of the 18th century in the UK, Kitney says, where master craftsmen like George Hepplewhite would labour to create one-off pieces of furniture.

"But we went from Hepplewhite to Ikea," he says. "That's what we're trying to achieve in synthetic biology."

 
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Crystal-free crystallography: tiny molecular sponges hold molecules in place for imaging

Crystal-free crystallography: tiny molecular sponges hold molecules in place for imaging | Amazing Science | Scoop.it

Crystallography, the technique that revealed DNA's double helix and the shapes of thousands of other molecules is getting an upgrade.

A method described in Nature  makes X-ray crystallography of small molecules simpler, faster and more sensitive, largely doing away with the laborious task of coaxing molecules to form crystals. Instead, porous scaffolding holds molecules in the orderly arrangement needed to discern their structure with X-rays.

 

"You could call it crystal-free crystallography," says Jon Clardy, a biological chemist at Harvard Medical School.

 

X-ray crystallography is one of the most important techniques in science, because it is one of only a few ways to directly determine the shape of large molecules. It does this by blasting molecules with X-rays and measuring how their rays are diffracted. Transforming these reflections into molecular models isn’t simple. But cajoling many molecules to crystallize is tedious and time-consuming — like getting a puppy to sit still for a photograph — and, Clardy says, the biggest bottle-neck in X-ray crystallography.


“Some crystallize easily, some crystallize hardly and some are impossible to crystallize, if they are liquid compounds,” says Makoto Fujita, a chemist at the University of Tokyo who led the work along with colleague Yasuhide Inokuma.


The team grew materials called metal-organic frameworks, which had large, regularly spaced cavities. These materials acted as 'crystalline sponges', mopping up tiny quantities of small molecules after a short incubation period and holding them in an ordered arrangement within a cage-like scaffold. The sponges were then subjected to X-ray diffraction.

 

In a blind test, the researchers used their technique to correctly determine the shape of several small molecules, the structures of which were already known. More impressively, the method allowed the authors to determine the structure of miyakosyne A, a chemical made in very small quantities by a species of sea sponge. The molecule has evaded crystallization because its sinewy shape causes it to flop around.

 

“It’s a remarkable achievement,” says Clardy. He thinks the technique will help researchers to mine marine life, soil bacteria and other organisms for compounds that might have uses in, for example, cancer drugs, because it is often difficult to determine the shape of these molecules from the small quantities found in nature. “I think this could be — to use an overused word — transformational,” Clardy says.

 

In its current form, the new technique isn’t applicable to proteins, because the pockets in the crystalline sponge are not big enough. But Fujita says his team is trying to make sponges with larger pockets. “Our next grand challenge is to apply this method to protein crystallography,” he says.


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Engineered artificial human livers for drug testing and discovery

Engineered artificial human livers for drug testing and discovery | Amazing Science | Scoop.it

Institute of Bioengineering and Nanotechnology (IBN) researchers have engineered an artificial human liver that mimics the natural tissue environment closely.

 

The development makes it possible for companies to predict the toxicity of new drugs earlier, potentially speeding up the drug development process and reducing the cost of manufacturing

 

 


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Engineered immune cells battle acute leukemia into retreat

Engineered immune cells battle acute leukemia into retreat | Amazing Science | Scoop.it

Modified T cells seek out and destroy blood cancer.

 

Genetically engineered immune cells can drive an aggressive type of leukemia into retreat, a small clinical trial suggests. The results of the trial — done in five patients with acute lymphoblastic leukemia and represent the latest success for a 'fringe' therapy in which a type of immune cell called T cells are extracted from a patient, genetically modified, and then reinfused back. In this case, the T cells were engineered to express a receptor for a protein on other immune cells, known as B cells, found in both healthy and cancerous tissue.


When reintroduced into the patients, the tricked T cells quickly homed in on their targets. “All of our patients very rapidly cleared the tumor,” says Michel Sadelain, a researcher at the Memorial Sloan-Kettering Cancer Center in New York and an author of the study. The treatment “worked much faster than we thought”.

The technique has already shown promise against chronic leukemia, but there were doubts about whether it could take on the faster-growing acute lymphoblastic leukemia, a tenacious disease that kills more than 60% of those afflicted.  

Carl June, an immunologist at the University of Pennsylvania in Philadelphia and a pioneer in engineering T cells to fight cancer, says that he is surprised that the method worked so well against such a swift-growing cancer. The next step, he says, is to move the technique out of the ‘boutique’ academic cancer centres that developed it and into multicentre clinical trials.

 

Oncologist Renier Brentjens, also at Memorial Sloan-Kettering Cancer Center, remembers the day that he had to tell one of the patients in the trial that the weeks of high-dose chemotherapy the 58-year-old man had endured had not worked after all. “It was painful to have that conversation,” says Brentjens. “He tells me now it was the worst news he has ever heard in his life.”

 

Another month in the hospital on intensive chemotherapy drugs did nothing to help. By the time the man started the trial, 70% of his bone marrow was tumour. Brentjens, Sadelain and their colleagues then extracted T cells from the patient and engineered them to express a ‘chimeric antigen receptor’, or CAR, that would target cells expressing a protein called CD19. Because CD19 is found on both healthy and cancerous B cells, the engineered T cells were unable to discriminate between the two. However, patients can live without B cells.


By two weeks after the procedure, the patient was showing signs of improvement. The treatment had driven his cancer into remission — as it did for the other four patients in the trial — so he became eligible for a bone-marrow transplant. A hundred days later, he is doing well, says Brentjens. Four of the five patients were well enough to receive transplants; the remaining patient relapsed and was ineligible.

 

Pharmaceutical firms have tended to be wary of the CAR technique because it is technically challenging, must be personalized to the patient and faces an untested path to regulatory approval, says Steven Rosenberg, head of the tumour immunology section at the National Cancer Institute in Bethesda, Maryland.

 

But this seems to be changing. Rosenberg points to a collaboration formed in August last year between June's group and the drug giant Novartis, as well as the launch of several small CAR-focused biotechnology firms. And Sadelein says that he is an investigator on a trial with the Dana-Farber Cancer Institute in Boston, Massachusetts, to test whether the technique can be exported to other treatment centers, among other outcomes.

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Elias Açaf's comment, June 1, 2013 10:17 AM
so interesting !