Amazing Science
832.3K views | +139 today
Follow
Amazing Science
Amazing science facts - 3D_printing • aging • AI • anthropology • art • astronomy • bigdata • bioinformatics • biology • biotech • chemistry • computers • cosmology • education • environment • evolution • future • genetics • genomics • geosciences • green_energy • history • language • map • material_science • math • med • medicine • microscopy • nanotech • neuroscience • paleontology • photography • photonics • physics • postings • robotics • science • technology • video
Your new post is loading...
Scooped by Dr. Stefan Gruenwald
Scoop.it!

Why Crispr-Cas9 Gene-Editing Technology Has Scientists Excited

Why Crispr-Cas9 Gene-Editing Technology Has Scientists Excited | Amazing Science | Scoop.it
Researchers are exploring the idea of treating disease by replacing the defective gene causing the trouble


A new technology for “editing” defective genes has raised hopes for a future generation of medicines treating intractable diseases like cancer, cystic fibrosis and sickle-cell anemia. Such drugs could home in on a specific gene causing a disease, then snip it out and, if necessary, replace it with a healthy segment of DNA. Drugs of this type wouldn’t hit the mass market for years, if ever; pharmaceutical firms are only now exploring how to make drugs using the gene-editing technology, called Crispr-Cas9. But the approach offers tremendous potential for developing new treatments for diseases caused by a mutated gene.


“What if you could go right to the root cause of that disease and repair the broken gene? That’s what people are excited about,” says Katrine Bosley, chief executive of privately held Editas Medicine. Its projects include developing a gene-editing drug treating one type of Leber congenital amaurosis, a rare disease that causes blindness in children.


Crispr-Cas9 isn’t the only technology capable of editing genes, but researchers consider it easier to use than other methods, says Dana Carroll, a professor of biochemistry at the University of Utah School of Medicine, who helped pioneer another gene-editing approach called zinc finger nucleases.


Among other efforts under way using Crispr-Cas9 technology, privately held Intellia Therapeutics Inc., in partnership with Novartis AG, is probing how to create a gene-editing drug that could harness the immune system to fight certain blood cancers. The two companies are also exploring the treatment of hereditary blood disorders like sickle-cell anemia and beta thalassemia.


Intellia CEO Nessan Bermingham says drugs based on Crispr-Cas9 promise to complement the pills and biotech drugs currently available, targeting diseases that aren’t well treated by existing therapies. “This is a new tool to target and treat disease,” he says. Industry and academic laboratories are also using the technology for more immediate effect: to genetically engineer mice and other animals so that they have humanlike diseases that researchers can then readily study.


Using Crispr-Cas9 to make the animal models is “much quicker, easier than the other methods that have been available,” says Tim Harris, senior vice president of precision medicine at Biogen Inc. The company is using the technology to study amyotrophic lateral sclerosis, or Lou Gehrig’s disease, which has lacked good animal models.


Crispr-Cas9 attracted notoriety in April, when Chinese scientists reported trying to repair the genes that cause beta thalassemia in 86 human embryos obtained from a fertilization clinic. The work raised fears that gene editing could be used to tweak babies in many ways before they were born.


more...
Rescooped by Dr. Stefan Gruenwald from Medical Science
Scoop.it!

New Candidate Brings us One Step Closer to an HIV Vaccine

New Candidate Brings us One Step Closer to an HIV Vaccine | Amazing Science | Scoop.it

Despite more than 30 years of intense research, a cure or vaccine for HIV still continues to elude us. But scientists are not quitting, and slowly but surely they seem to be making promising progress in this field. For example, two new mouse studies have just come out that demonstrate that a novel vaccine candidate is able to prompt the beginnings of an immune reaction needed to prevent infection. While the results are not the “breakthrough” everyone is looking for, they are certainly a stride in the right direction.


Vaccines can be made in a variety of different ways, for example by inactivating whole pathogens or isolating particular components of them, both with the ultimate goal of stimulating a defense response from the immune system, readying it for any future assaults. But the problem with pesky HIV is that it mutates remarkably rapidly, changing its components so that they become unrecognizable by the immune system. This means that should a vaccine be successful in inducing the production of protective antibodies, they usually have such a narrow window of activity that they are effectively useless.


But there are some antibodies that are different, called broadly neutralizing antibodies (bNAbs), and scientists have high hopes that these may hold the key to producing a successful HIV vaccine. As the name suggests, rather than being specific to just one target, these antibodies are able to recognize and inhibit a range of HIV variants, or strains, and thus are much more therapeutically useful. Although a subset of HIV-positive individuals produce these antibodies, scientists have so far failed to induce their production via vaccination.


Many researchers believe the key to achieving this is by presenting the body with multiple targets, or antigens, that differ slightly, training the immune system to recognize and hone in on the more conserved elements of HIV that are found in different strains. One particular molecule that scientists are interested in is an antigen called eOD-GT8, which was engineered by researchers, headed by William Schief, at The Scripps Research Institute.


Rather than attempting to directly elicit bNAbs, this antigen is designed to stimulate the production of precursor antibodies that will eventually mature into bNAbs following prolonged exposure to the virus, The Scientist explains. So by starting off with these immature antibodies, scientists hypothesize it may be possible to encourage them to develop into bNAbs over time by gradually exposing the immune system to slightly different HIV antigens, forcing the antibodies to mutate in order to recognize more conserved regions of the virus.


When testing this molecule out in mice genetically engineered to produce antibodies similar to those found in humans, the researchers found that it was indeed able to elicit these first-line antibodies. Additionally, they found it also created a pool of antibody-producing “memory” B cells that the researchers believe could be boosted through exposure to different antigens, sort of like receiving booster shots. These findings have been reported in Science.


Via Steven Krohn
more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

First working synthetic immune organ with controllable antibodies

First working synthetic immune organ with controllable antibodies | Amazing Science | Scoop.it

Cornell University engineers have created a functional, synthetic immune organoid (a lab-grown ball of cells with some of the features of a normal organ) that produces antibodies. The engineered organ has implications for everything from rapid production of immune therapies to new frontiers in cancer or infectious disease research. The first-of-its-kind immune organoid was created in the lab of Ankur Singh, assistant professor of mechanical and aerospace engineering, who applies engineering principles to the study and manipulation of the human immune system.


The synthetic organ is bio-inspired by secondary immune organs like the lymph node or spleen. It is made from a hydrogel (a soft, nanocomposite gelatin-like biomaterial), reinforced with silicate nanoparticles to keep the structure from melting at body temperature. This biomaterial is also seeded with B cells. It mimics the body’s normal anatomical microenvironment of lymphoid tissue, which produces lymphocytes and antibodies in the lymph nodes, thymus, tonsils, and spleen.


Like a real organ, the organoid converts B cells — which make antibodies that respond to infectious invaders — into germinal centers, which are clusters of B cells that activate, mature and mutate their antibody genes when the body is under attack. Germinal centers are a sign of infection and are not present in healthy immune organs.


The engineers have demonstrated how they can control this immune response in the organ and tune how quickly the B cells proliferate, get activated and change their antibody types. According to their paper, their 3-D organ outperforms existing 2-D lab cultures and can produce activated B cells up to 100 times faster.


According to Singh, the organoid could lead to increased understanding of B cell functions, an area of study that typically relies on animal models to observe how the cells develop and mature, and could also be used to study specific infections and how the body produces antibodies to fight those infections — from Ebola to HIV. “You can use our system to force the production of immunotherapeutics at much faster rates,” he said. Such a system also could be used to test toxic chemicals and environmental factors that contribute to infections or organ malfunctions.


The process of B cells becoming germinal centers is not well understood, and in fact, when the body makes mistakes in the genetic rearrangement related to this process, blood cancer can result. “In the long run, we anticipate that the ability to drive immune reaction ex vivo [outside the body] at controllable rates grants us the ability to reproduce immunological events with tunable parameters for better mechanistic understanding of B cell development and generation of B cell tumors, as well as screening and translation of new classes of drugs,” Singh said.

more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

First baby ever born from ovary frozen in mother's childhood

First baby ever born from ovary frozen in mother's childhood | Amazing Science | Scoop.it

A woman in Belgium is the first in the world to give birth to a baby using transplanted ovarian tissue frozen when she was still a child, doctors say. The 27-year-old had an ovary removed at age 13, just before she began invasive treatment for sickle cell anaemia.


Her remaining ovary failed following the treatment, meaning she would have been unlikely to conceive without the transplant. Experts hope that this procedure could eventually help other young patients. The woman gave birth to a healthy boy in November 2014, and details of the case were published on Wednesday in the journal Human Reproduction.

The woman, who has asked to remain anonymous, was diagnosed with sickle cell anaemia at the age of five. She emigrated from the Republic of Congo to Belgium where doctors decided her disease was so severe that she needed a bone marrow transplant using her brother's matching tissue.
more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

Biochemists devise new technique for blueprinting cell membrane proteins

Biochemists devise new technique for blueprinting cell membrane proteins | Amazing Science | Scoop.it
Biochemists from Trinity College Dublin have devised a new technique that will make the difficult but critical job of blueprinting certain proteins considerably faster, easier and cheaper.


The breakthrough will make a big splash in the field of drug discovery and development, where precise protein structure blueprints can help researchers understand how individual proteins work. Critically, these blueprints can show weaknesses that allow drug developers to draw up specific battle plans in the fight against diseases and infections.

Professor of Membrane Structural and Functional Biology at Trinity, Martin Caffrey, is the senior author of the research, which has just been published in the international peer-reviewed journal Acta Crystallographica D.


He said: "This is a truly exciting development. We have demonstrated the method on a variety of cell membrane proteins, some of which act as transporters. It will work with existing equipment at a host of facilities worldwide, and it is very simple to implement."


Over 50% of drugs on the market target cell membrane proteins, which are vital for the everyday functioning of complex cellular processes. They act as transporters to ensure that specific molecules enter and leave our cells, as signal interpreters important in decoding messages and initiating responses, and as agents that speed up appropriate responses.


The major challenge facing researchers is the production of large membrane protein crystals, which are used to determine the precise 3-D structural blueprints. That challenge has now been lessened thanks to the Trinity biochemists' advent - the in meso in situ serial crystallography (IMISX) method.


Beforehand, researchers needed to harvest protein crystals and cool them at inhospitable temperatures in a complex set of events that was damaging, inefficient and prone to error. The IMISX method allows researchers to determine structural blueprints as and where the crystals grow.


Professor Caffrey added: "The best part of this is that these proteins are as close to being 'live' and yet packaged in the crystals we need to determine their structure as they could ever be. As a result, this breakthrough is likely to supplant existing protocols and will make the early stages of drug development considerably more efficient."

more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

Muscles engineered to be photosensitive could lead to treatments for paralysis

Muscles engineered to be photosensitive could lead to treatments for paralysis | Amazing Science | Scoop.it

Scientists have genetically engineered muscles to move in response to pulses of light. The technique, demonstrated on vocal cords removed from mice, is reported on 2 June in Nature Communications1. Researchers say that it could probe how muscles function — and might eventually help to treat people who have a paralysis that interferes with speech and breathing.  The work relies on a method called optogenetics, which can make cells that usually respond to electrical signals also react to light. The approach alters mammalian cells by inserting a gene for a protein such as channelrhodopsin, which in its natural setting allows blue-green algae to swim towards or away from light.


Optogenetics was first used in 2005 to modify neurons2, and has since become a standard tool to study the brain and nervous system. Applications outside neuroscience, however, are less common. The latest study is fascinating, says Julio Vergara, a physiologist at the University of California, Los Angeles, who studies how electrical signals cause muscles to contract. “It shows the potential use of this very powerful technique for very important medical problems,” he says.


The study's authors had previously used optogenetics to engineer heart muscle in mice3 — light caused parts of the heart to beat out of sync, simulating arrhythmias. The latest research extends this to muscles that move under conscious command.


“Skeletal muscles follow different rules than the heart,” says Philipp Sasse, a co-author of the study and a physiologist at the University of Bonn in Germany. “Each fibre in a skeletal muscle can contract separately, which allows controlling movements as well as muscle strength very precisely.”

more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

Immunotherapy shows promise in fighting cancer

Immunotherapy shows promise in fighting cancer | Amazing Science | Scoop.it

Researchers meeting in Chicago are hailing what they believe may be a potent new weapon in the fight against cancer: the body's own immune system.


An international study found that a combination of two drugs that helped allow the immune system to fight the cancer -- ipilimumab and nivolumab -- stopped the deadly skin cancer melanoma from advancing for nearly a year in 58% of the cases. Melanoma, though a skin cancer, can spread to the lungs, liver, bone, lymph nodes and brain.


Other studies have shown promise in treating lung cancer. The research is being presented in Chicago at the annual conference of the American Society of Clinical Oncology and published inThe New England Journal of Medicine.


Those involved in the fight against cancer are divided as to just how excited to get over the promise of immunotherapy in battling cancer.


"Immunotherapy drugs have already revolutionized melanoma treatment, and now we're seeing how they might be even more powerful when they're combined," said Dr. Steven O'Day, an expert with the American Society of Clinical Oncology.


"But the results also warrant caution -- the nivolumab and ipilimumab combination used in this study came with greater side effects, which might offset its benefits for some patients. Physicians and patients will need to weigh these considerations carefully," O'Day said.


In the study, 36% of the patients receiving the two-drug combination had to stop the therapy due to side effects. Both drugs are made by Bristol-Myers Squibb, the sponsors of the study. And Nell Barrie, a spokeswoman for Cancer Research UK, while calling the results "encouraging" and "promising," told CNN that much remains to be learned and the new drugs would not replace any of the existing cancer treatments.


Surgery, she said, would remain vital. So, too, would chemotherapy and radiotherapy, she said. She noted that researchers had yet to study the long-term survival rates for immunotherapy. And the side effects can include inflammation of the stomach and bowel serious enough to require hospitalization, she said.


But Dr. James Larkin, the lead author of the melanoma study, called the results a game changer. "We've seen these drugs working in a wide range of cancers, and I think we are at the beginning of a new era in treating cancer," Larkin said.

more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

Rapid dynamic reprogramming of matter

Rapid dynamic reprogramming of matter | Amazing Science | Scoop.it

Engineering switchable reconfigurations in DNA-controlled nanoparticle arrays could lead to dynamic energy-harvesting or responsive optical materials


The rapid development of self-assembly approaches has enabled the creation of materials with desired organization of nanoscale components. However, achieving dynamic control, wherein the system can be transformed on demand into multiple entirely different states, is typically absent in atomic and molecular systems and has remained elusive in designed nanoparticle systems. Here, we demonstrate with in situ small-angle X-ray scattering that, by using DNA strands as inputs, the structure of a three-dimensional lattice of DNA-coated nanoparticles can be switched from an initial ‘mother phase into one of multiple ‘daughter phases. The introduction of different types of reprogramming DNA strands modifies the DNA shells of the nanoparticles within the superlattice, thereby shifting interparticle interactions to drive the transformation into a particular daughter phase. Moreover, we mapped quantitatively with free-energy calculations the selective reprogramming of interactions onto the observed daughter phases.


Scientists at the U.S. Department of Energy’s Brookhaven National Laboratory have developed the capability of creating dynamic nanomaterials — ones whose structure and associated properties can be switched, on-demand. In a paper appearing in Nature Materials, they describe a way to selectively rearrange nanoparticles in three-dimensional arrays to produce different configurations, or “phases,” from the same nano-components.


“One of the goals in nanoparticle self-assembly has been to create structures by design,” said Oleg Gang, who led the work at Brookhaven’s Center for Functional Nanomaterials (CFN), a DOE Office of Science User Facility. “Until now, most of the structures we’ve built have been static.” KurzweilAI covered that development in a previous article, “Creating complex structures using DNA origami and nanoparticles.”


The new advance in nanoscale engineering builds on that previous work in developing ways to get nanoparticles to self-assemble into complex composite arrays, including linking them together with tethers constructed of complementary strands of synthetic DNA.


“We know that properties of materials built from nanoparticles are strongly dependent on their arrangements,” said Gang. “Previously, we’ve even been able to manipulate optical properties by shortening or lengthening the DNA tethers. But that approach does not permit us to achieve a global reorganization of the entire structure once it’s already built.”

more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

Phase III Virotherapy uses modified herpes virus to attack melanoma cells

Phase III Virotherapy uses modified herpes virus to attack melanoma cells | Amazing Science | Scoop.it

Patients with aggressive skin cancer - melanoma - have been treated successfully using a drug based on the herpes virus, in a trial that could pave the way for a new generation of cancer treatments. The findings mark the first positive phase 3 trial results for cancer “virotherapy”, where one disease is harnessed and used to attack another. If approved, the drug, called T-VEC, could be more widely available for cancer patients by next year, scientists predicted.


Crucially, the therapy has the potential to overcome cancer even when the disease has spread to organs throughout the body, offering hope in future to patients who have been faced with the bleakest prognosis. Kevin Harrington, professor of biological cancer therapies at the Institute of Cancer Research London, who led the work, said: “This is the big promise of this treatment. It’s the first time a virotherapy has been shown to be successful in a phase 3 trial.”


In the trial, involving more than 400 patients with aggressive melanoma, one in four patients responded to the treatment, and 16% were still in remission after six months. About 10% of the patients treated had “complete remission”, with no detectable cancer remaining - considered a cure if the patient is still cancer-free five years after diagnosis.


The results are especially encouraging, Harrington said, because all the patients had inoperable, relapsed or metastatic melanoma with no conventional treatment options available to them. “They had disease that ranged from dozens to hundreds of deposits of melanoma on a limb all the way to patients where cancer had spread to the lungs and liver,” he said.

more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

Germ Line Engineering with CRISPR Leads to Designer Human Embryos

Germ Line Engineering with CRISPR Leads to Designer Human Embryos | Amazing Science | Scoop.it

How easy would it be to edit a human embryo using CRISPR? Very easy, experts say. “Any scientist with molecular biology skills and knowledge of how to work with embryos is going to be able to do this,” says Jennifer Doudna, a biologist at the University of California, Berkeley, who in 2012 co-discovered how to use CRISPR to edit genes.


To find out how it could be done, I visited the lab of Guoping Feng, a biologist at MIT’s McGovern Institute for Brain Research, where a colony of marmoset monkeys is being established with the aim of using CRISPR to create accurate models of human brain diseases. To create the models, Feng will edit the DNA of embryos and then transfer them into female marmosets to produce live monkeys. One gene Feng hopes to alter in the animals is SHANK3. The gene is involved in how neurons communicate; when it’s damaged in children, it is known to cause autism.


Feng said that before CRISPR, it was not possible to introduce precise changes into a primate’s DNA. With CRISPR, the technique should be relatively straightforward. The CRISPR system includes a gene-snipping enzyme and a guide molecule that can be programmed to target unique combinations of the DNA letters, A, G, C, and T; get these ingredients into a cell and they will cut and modify the genome at the targeted sites.


But CRISPR is not perfect—and it would be a very haphazard way to edit human embryos, as Feng’s efforts to create gene-edited marmosets show. To employ the CRISPR system in the monkeys, his students simply inject the chemicals into a fertilized egg, which is known as a zygote—the stage just before it starts dividing.


Feng said the efficiency with which CRISPR can delete or disable a gene in a zygote is about 40 percent, whereas making specific edits, or swapping DNA letters, works less frequently—more like 20 percent of the time. Like a person, a monkey has two copies of most genes, one from each parent. Sometimes both copies get edited, but sometimes just one does, or neither. Only about half the embryos will lead to live births, and of those that do, many could contain a mixture of cells with edited DNA and without. If you add up the odds, you find you’d need to edit 20 embryos to get a live monkey with the version you want.


That’s not an insurmountable problem for Feng, since the MIT breeding colony will give him access to many monkey eggs and he’ll be able to generate many embryos. However, it would present obvious problems in humans. Putting the ingredients of CRISPR into a human embryo would be scientifically trivial. But it wouldn’t be practical for much just yet. This is one reason that many scientists view such an experiment (whether or not it has really occurred in China) with scorn, seeing it more as a provocative bid to grab attention than as real science. Rudolf Jaenisch, an MIT biologist who works across the street from Feng and who in the 1970s created the first gene-modified mice, calls attempts to edit human embryos “totally premature.” He says he hopes these papers will be rejected and not published. “It’s just a sensational thing that will stir things up,” says Jaenisch. “We know it’s possible, but is it of practical use? I kind of doubt it.”


Among other problems, CRISPR can introduce off-target effects or change bits of the genome far from where scientists had intended. Any human embryo altered with CRISPR today would carry the risk that its genome had been changed in unexpected ways. But, Feng said, such problems may eventually be ironed out, and edited people will be born. “To me, it’s possible in the long run to dramatically improve health, lower costs. It’s a kind of prevention,” he said. “It’s hard to predict the future, but correcting disease risks is definitely a possibility and should be supported. I think it will be a reality.”


Elsewhere in the Boston area, scientists are exploring a different approach to engineering the germ line, one that is technically more demanding but probably more powerful. This strategy combines CRISPR with unfolding discoveries related to stem cells. Scientists at several centers, including Church’s, think they will soon be able to use stem cells to produce eggs and sperm in the laboratory. Unlike embryos, stem cells can be grown and multiplied. Thus they could offer a vastly improved way to create edited offspring with CRISPR. The recipe goes like this: First, edit the genes of the stem cells. Second, turn them into an egg or sperm. Third, produce an offspring.


Some investors got an early view of the technique on December 17, at the Benjamin Hotel in Manhattan, during commercial presentations by OvaScience. The company, which was founded four years ago, aims to commercialize the scientific work of David Sinclair, who is based at Harvard, and Jonathan Tilly, an expert on egg stem cells and the chairman of the biology department at Northeastern University (see “10 Emerging Technologies: Egg Stem Cells,”May/June 2012). It made the presentations as part of a successful effort to raise $132 million in new capital during January.


During the meeting, Sinclair, a velvet-voiced Australian whom Time last year named one of the “100 Most Influential People in the World,” took the podium and provided Wall Street with a peek at what he called “truly world-changing” developments. People would look back at this moment in time and recognize it as a new chapter in “how humans control their bodies,” he said, because it would let parents determine “when and how they have children and how healthy those children are actually going to be.”


The company has not perfected its stem-cell technology—it has not reported that the eggs it grows in the lab are viable—but Sinclair predicted that functional eggs were “a when, and not an if.” Once the technology works, he said, infertile women will be able to produce hundreds of eggs, and maybe hundreds of embryos. Using DNA sequencing to analyze their genes, they could pick among them for the healthiest ones.

more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

New algorithm for 3D structures from 2D images will speed up protein structure discovery 100,000 fold

New algorithm for 3D structures from 2D images will speed up protein structure discovery 100,000 fold | Amazing Science | Scoop.it

One of the great challenges in molecular biology is to determine the three-dimensional structure of large biomolecules such as proteins. But this is a famously difficult and time-consuming task. The standard technique is x-ray crystallography, which involves analyzing the x-ray diffraction pattern from a crystal of the molecule under investigation. That works well for molecules that form crystals easily.


But many proteins, perhaps most, do not form crystals easily. And even when they do, they often take on unnatural configurations that do not resemble their natural shape. So finding another reliable way of determining the 3-D structure of large biomolecules would be a huge breakthrough. Today, Marcus Brubaker and a couple of pals at the University of Toronto in Canada say they have found a way to dramatically improve a 3-D imaging technique that has never quite matched the utility of x-ray crystallography.


The new technique is based on an imaging process called electron cryomicroscopy. This begins with a purified solution of the target molecule that is frozen into a thin film just a single molecule thick. This film is then photographed using a process known as transmission electron microscopy—it is bombarded with electrons and those that pass through are recorded. Essentially, this produces two-dimensional “shadowgrams” of the molecules in the film. Researchers then pick out each shadowgram and use them to work out the three-dimensional structure of the target molecule.


This process is hard for a number of reasons. First, there is a huge amount of noise in each image so even the two-dimensional shadow is hard to make out. Second, there is no way of knowing the orientation of the molecule when the shadow was taken so determining the 3-D shape is a huge undertaking.


The standard approach to solving this problem is little more than guesswork. Dream up a potential 3-D structure for the molecule and then rotate it to see if it can generate all of the shadowgrams in the dataset. If not, change the structure, test it, and so on.


Obviously, this is a time-consuming process. The current state-of-the-art algorithm running on 300 cores takes two weeks to find the 3-D structure of a single molecule from a dataset of 200,000 images.

more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

DNA 'cage' holding a payload of drugs set to begin clinical trial soon

DNA 'cage' holding a payload of drugs set to begin clinical trial soon | Amazing Science | Scoop.it

Ido Bachelet, who was previously at Harvard’s Wyss Institute in Boston, Massachusetts and Israel’s Bar-Ilan University, intends to treat a patient who has been given six months to live. The patient is set to receive an injection of DNA nanocages designed to interact with and destroy leukemia cells without damaging healthy tissue. Speaking in December, he said: ‘Judging from what we saw in our tests, within a month that person is going to recover.


DNA nanocages can be programmed to independently recognize target cells and deliver payloads, such as cancer drugs, to these cells. 

George Church, who is involved in the research at the Wyss Institute explained the idea of the microscopic robots is to make a ‘cage’ that protects a fragile or toxic payload and ‘only releases it at the right moment.’


These nanostructures are built upon a single strand of DNA which is combined with short synthetic strands of DNA designed by the experts.  When mixed together, they self-assemble into a desired shape, which in this case looks a little like a barrel.


Dr Bachelet said: 'The nanorobot we designed actually looks like an open-ended barrel, or clamshell that has two halves linked together by flexible DNA hinges and the entire structure is held shut by latches that are DNA double helixes.’


A complementary piece of DNA is attached to a payload, which enables it to bind to the inside of the biological barrel. The double helixes stay closed until specific molecules or proteins on the surface of cancer cells act as a 'key' to open the ‘barrel’ so the payload can be deployed.


'The nanorobot is capable of recognizing a small population of target cells within a large healthy population,’ Dr Bachelet continued.

‘While all cells share the same drug target that we want to attack, only those target cells that express the proper set of keys open the nanorobot and therefore only they will be attacked by the nanorobot and by the drug.’


The team has tested its technique in animals as well as cell cultures and said the ‘nanorobot attacked these [targets] with almost zero collateral damage.’ The method has many advantages over invasive surgery and blasts of drugs, which can be ‘as painful and damaging to the body as the disease itself,’ the team added.

more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

Lipid-nanoparticle-encapsulated siRNAs cure monkeys infected with West African Ebola strain

Lipid-nanoparticle-encapsulated siRNAs cure monkeys infected with West African Ebola strain | Amazing Science | Scoop.it
An experimental drug has cured monkeys infected with the strain of the Ebola virus present in West Africa, US-based scientists say.


An experimental drug has cured monkeys infected with the Ebola virus, US-based scientists have said. The treatment, known as TKM-Ebola-Guinea, targets the Makona strain of the virus, which caused the current deadly outbreak in West Africa. All three monkeys receiving the treatment were healthy when the trial ended after 28 days; three untreated monkeys died within nine days. Scientists cautioned that the drug's efficacy has not been proven in humans. At present, there are no treatments or vaccines for Ebola that have been proven to work in humans.


University of Texas scientist Thomas Geisbert, who was the senior author of the study published in the journal Nature, said: "This is the first study to show post-exposure protection... against the new Makona outbreak strain of Ebola-Zaire virus." Results from human trials with the drug are expected in the second half of this year.


The current outbreak of Ebola virus in West Africa is unprecedented, causing more cases and fatalities than all previous outbreaks combined, and has yet to be controlled1. Several post-exposure interventions have been employed under compassionate use to treat patients repatriated to Europe and the United States2. However, the in vivo efficacy of these interventions against the new outbreak strain of Ebola virus is unknown.


In the current study, the scientists show that lipid-nanoparticle-encapsulated short interfering RNAs (siRNAs) rapidly adapted to target the Makona outbreak strain of Ebola virus are able to protect 100% of rhesus monkeys against lethal challenge when treatment was initiated at 3 days after exposure while animals were viremic and clinically ill.


Although all infected animals showed evidence of advanced disease including abnormal hematology, blood chemistry and coagulopathy, siRNA-treated animals had milder clinical features and fully recovered, while the untreated control animals succumbed to the disease. These results represent the first successful demonstration of therapeutic anti-Ebola virus efficacy against the new outbreak strain in non-human primates and highlight the rapid development of lipid-nanoparticle-delivered siRNA as a countermeasure against this highly lethal human disease.

more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

Expanding the DNA alphabet: ‘extra’ DNA base (5-formylcytosine) found to be stable in mammals

Expanding the DNA alphabet: ‘extra’ DNA base (5-formylcytosine) found to be stable in mammals | Amazing Science | Scoop.it
A rare DNA base, previously thought to be a temporary modification, has been shown to be stable in mammalian DNA, suggesting that it plays a key role in cellular function.


Researchers from the University of Cambridge and the Babraham Institute have found that a naturally occurring modified DNA base appears to be stably incorporated in the DNA of many mammalian tissues, possibly representing an expansion of the functional DNA alphabet.


The new study, published in the journal Nature Chemical Biology, has found that this rare ‘extra’ base, known as 5-formylcytosine (5fC) is stable in living mouse tissues. While its exact function is yet to be determined, 5fC’s physical position in the genome makes it likely that it plays a key role in gene activity.


“This modification to DNA is found in very specific positions in the genome – the places which regulate genes,” said the paper’s lead author Dr Martin Bachman, who conducted the research while at Cambridge’s Department of Chemistry. “In addition, it’s been found in every tissue in the body – albeit in very low levels.”


“If 5fC is present in the DNA of all tissues, it is probably there for a reason,” said Professor Shankar Balasubramanian of the Department of Chemistry and the Cancer Research UK Cambridge Institute, who led the research. “It had been thought this modification was solely a short-lived intermediate, but the fact that we’ve demonstrated it can be stable in living tissue shows that it could regulate gene expression and potentially signal other events in cells.”


Since the structure of DNA was discovered more than 60 years ago, it’s been known that there are four DNA bases: G, C, A and T (Guanine, Cytosine, Adenine and Thymine). The way these bases are ordered determines the makeup of the genome. In addition to G, C, A and T, there are also small chemical modifications, or epigenetic marks, which affect how the DNA sequence is interpreted and control how certain genes are switched on or off. The study of these marks and how they affect gene activity is known as epigenetics.


5fC is one of these marks, and is formed when enzymes called TET enzymes add oxygen to methylated DNA – a DNA molecule with smaller molecules of methyl attached to the cytosine base. First discovered in 2011, it had been thought that 5fC was a ‘transitional’ state of the cytosine base which was then being removed from DNA by dedicated repair enzymes. However, this new research has found that 5fC can actually be stable in living tissue, making it likely that it plays a key role in the genome.


Using high-resolution mass spectrometry, the researchers examined levels of 5fC in living adult and embryonic mouse tissues, as well as in mouse embryonic stem cells – the body’s master cells which can become almost any cell type in the body.


They found that 5fC is present in all tissues, but is very rare, making it difficult to detect. Even in the brain, where it is most common, 5fC is only present at around 10 parts per million or less. In other tissues throughout the body, it is present at between one and five parts per million.


The researchers applied a method consisting of feeding cells and living mice with an amino acid called L-methionine, enriched for naturally occurring stable isotopes of carbon and hydrogen, and measuring the uptake of these isotopes to 5fC in DNA. The lack of uptake in the non-dividing adult brain tissue pointed to the fact that 5fC can be a stable modification: if it was a transient molecule, this uptake of isotopes would be high.


The researchers believe that 5fC might alter the way DNA is recognised by proteins. “Unmodified DNA interacts with a specific set of proteins, and the presence of 5fC could change these interactions either directly or indirectly by changing the shape of the DNA duplex,” said Bachman. “A different shape means that a DNA molecule could then attract different proteins and transcription factors, which could in turn change the way that genes are expressed.”

more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

Three-dimensional Nanowire Structures for Ultra-Fast Separation of DNA, Protein and RNA

Three-dimensional Nanowire Structures for Ultra-Fast Separation of DNA, Protein and RNA | Amazing Science | Scoop.it

Separation and analysis of biomolecules represent crucial processes for biological and biomedical engineering development. However, separation resolution and speed for biomolecules analysis still require improvements. To achieve separation and analysis of biomolecules in a short time, the use of highly-ordered nanostructures fabricated by top-down or bottom-up approaches have been proposed. Here, a group of scientists reported on the use of three-dimensional (3D) nanowire structures embedded in microchannels fabricated by a bottom-up approach for ultrafast separation of small biomolecules, such as DNA, protein, and RNA molecules. The 3D nanowire structures could analyze a mixture of DNA molecules (50–1000 bp) within 50 s, a mixture of protein molecules (20–340 kDa) within 5 s, and a mixture of RNA molecules (100–1000 bases) within 25 s. The researchers observed the electrophoretic mobility difference of biomolecules as a function of molecular size in the 3D nanowire structures. Since the present methodology allows users to control the pore size of sieving materials by varying the number of cycles for nanowire growth, the 3D nanowire structures have a good potential for use as alternatives for other sieving materials. The presented method allows researchers to control the pore size between nanowires by varying the number of nanowire growth cycles and to select the pore size of the nanowires based on the analytical range of the target biomolecules.

more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

Transplantability of a circadian clock to a noncircadian organism

Transplantability of a circadian clock to a noncircadian organism | Amazing Science | Scoop.it

Circadian oscillators are post-translationally regulated and affect gene expression in autotrophic cyanobacteria. Oscillations are controlled by phosphorylation of the KaiC protein, which is modulated by the KaiA and KaiB proteins. However, it remains unclear how time information is transmitted to transcriptional output. A group of researchers now show reconstruction of the KaiABC oscillator in the noncircadian bacterium Escherichia coli. This orthogonal system shows circadian oscillations in KaiC phosphorylation and in a synthetic transcriptional reporter. Coexpression of KaiABC with additional native cyanobacterial components demonstrates a minimally sufficient set of proteins for transcriptional output from a native cyanobacterial promoter in E. coli. Together, these results demonstrate that a circadian oscillator is transplantable to a heterologous organism for reductive study as well as wide-ranging applications.

more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

Researchers targeting the host rather than the flu virus have success with new treatment tested in mice

Researchers targeting the host rather than the flu virus have success with new treatment tested in mice | Amazing Science | Scoop.it

The flu kills hundreds of thousands of people around the world every year, yet there is essentially only one class of drugs to fight the ever-changing virus. Cases of flu resistant to this class of drugs have already been reported and researchers worry a completely new strain of flu could evolve, leading to a pandemic like the one in 1918 that killed approximately 50 million people.


Many researchers are trying to develop new drugs to defeat the flu virus. But researchers at St. Michael’s Hospital had a completely different idea. People who die from the flu actually die from respiratory failure, when the lung’s tiny blood vessels start leaking fluid into the lung’s air sacs. Dr. Warren Lee, a researcher with the hospital’s Keenan Research Centre for Biomedical Sciences, wondered what would happen if someone developed a treatment that would prevent those blood vessels from leaking?


Working with mice, Dr. Lee tested a new drug developed by researchers at Sunnybrook Hospital that acts on the endothelial cells that line the blood vessels.


Their work, published today in the journal Scientific Reports, found that: The drug, Vasculotide, was effective against multiple strains of influenza, including the 2009 swine flu pandemic strain. Without the drug, 100 per cent of the mice died within one week. With the drug, more than 80 per cent survived.


In addition:

  • The drug worked even if it was administered days after the infection began. Traditional antiviral drugs such as Tamiflu must be started immediately.
  • The drug worked alone and in combination with antivirals.
  • It worked without compromising the body’s ability to mount an immune response to the virus.


Dr. Lee, a critical care physician and cell biologist, said that while this research was conducted in mice, he found the results exciting since the drug was effective in two different strains of mice and three different strains of flu. He said that since the mechanism of blood vessels leaking into lungs is common throughout animals, he was optimistic the drug could be effective in animals other than mice, including humans. St. Michael’s and Sunnybrook have jointly applied for a U.S. patent for the drug.

more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

CRISPR, a powerful gene-editing technology is the biggest game changer to hit biology since PCR

CRISPR, a powerful gene-editing technology is the biggest game changer to hit biology since PCR | Amazing Science | Scoop.it

Three years ago, Bruce Conklin came across a method that made him change the course of his lab. Conklin, a geneticist at the Gladstone Institutes in San Francisco, California, had been trying to work out how variations in DNA affect various human diseases, but his tools were cumbersome. When he worked with cells from patients, it was hard to know which sequences were important for disease and which were just background noise. And engineering a mutation into cells was expensive and laborious work. “It was a student's entire thesis to change one gene,” he says.


Then, in 2012, he read about a newly published technique1 called CRISPR that would allow researchers to quickly change the DNA of nearly any organism — including humans. Soon after, Conklin abandoned his previous approach to modelling disease and adopted this new one. His lab is now feverishly altering genes associated with various heart conditions. “CRISPR is turning everything on its head,” he says.


The sentiment is widely shared: CRISPR is causing a major upheaval in biomedical research. Unlike other gene-editing methods, it is cheap, quick and easy to use, and it has swept through labs around the world as a result. Researchers hope to use it to adjust human genes to eliminate diseases, create hardier plants, wipe out pathogens and much more besides. “I've seen two huge developments since I've been in science: CRISPR and PCR,” says John Schimenti, a geneticist at Cornell University in Ithaca, New York. Like PCR, the gene-amplification method that revolutionized genetic engineering after its invention in 1985, “CRISPR is impacting the life sciences in so many ways,” he says.


But although CRISPR has much to offer, some scientists are worried that the field's breakneck pace leaves little time for addressing the ethical and safety concerns such experiments can raise. The problem was thrust into the spotlight in April, when news broke that scientists had used CRISPR to engineer human embryos (see Nature 520, 593–595; 2015). The embryos they used were unable to result in a live birth, but the report2 has generated heated debate over whether and how CRISPR should be used to make heritable changes to the human genome. And there are other concerns. Some scientists want to see more studies that probe whether the technique generates stray and potentially risky genome edits; others worry that edited organisms could disrupt entire ecosystems.


“This power is so easily accessible by labs — you don't need a very expensive piece of equipment and people don't need to get many years of training to do this,” says Stanley Qi, a systems biologist at Stanford University in California. “We should think carefully about how we are going to use that power.”


Biologists have long been able to edit genomes with molecular tools. About ten years ago, they became excited by enzymes called zinc finger nucleases that promised to do this accurately and efficiently. But zinc fingers, which cost US$5,000 or more to order, were not widely adopted because they are difficult to engineer and expensive, says James Haber, a molecular biologist at Brandeis University in Waltham, Massachusetts. CRISPR works differently: it relies on an enzyme called Cas9 that uses a guide RNA molecule to home in on its target DNA, then edits the DNA to disrupt genes or insert desired sequences. Researchers often need to order only the RNA fragment; the other components can be bought off the shelf. Total cost: as little as $30. “That effectively democratized the technology so that everyone is using it,” says Haber. “It's a huge revolution.”


CRISPR methodology is quickly eclipsing zinc finger nucleases and other editing tools (see 'The rise of CRISPR'). For some, that means abandoning techniques they had taken years to perfect. “I'm depressed,” says Bill Skarnes, a geneticist at the Wellcome Trust Sanger Institute in Hinxton, UK, “but I'm also excited.” Skarnes had spent much of his career using a technology introduced in the mid-1980s: inserting DNA into embryonic stem cells and then using those cells to generate genetically modified mice. The technique became a laboratory workhorse, but it was also time-consuming and costly. CRISPR takes a fraction of the time, and Skarnes adopted the technique two years ago.


Researchers have traditionally relied heavily on model organisms such as mice and fruit flies, partly because they were the only species that came with a good tool kit for genetic manipulation. Now CRISPR is making it possible to edit genes in many more organisms. In April, for example, researchers at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, reported using CRISPR to study Candida albicans, a fungus that is particularly deadly in people with weakened immune systems, but had been difficult to genetically manipulate in the lab3. Jennifer Doudna, a CRISPR pioneer at the University of California, Berkeley, is keeping a list of CRISPR-altered creatures. So far, she has three dozen entries, including disease-causing parasites called trypanosomes and yeasts used to make biofuels.


more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

DNA methylation test makes it easier to pinpoint identical twin responsible for a crime

DNA methylation test makes it easier to pinpoint identical twin responsible for a crime | Amazing Science | Scoop.it
You can run, but you can't hide: A new DNA test makes it easier to differentiate between identical twins in forensic cases.


Although short tandem repeat profiling is extremely powerful in identifying individuals from crime scene stains, it is unable to differentiate between monozygotic (MZ) twins. Efforts to address this include mutation analysis through whole genome sequencing and through DNA methylation studies. Methylation of DNA is affected by environmental factors; thus, as MZ twins age, their DNA methylation patterns change. This can be characterized by bisulfite treatment followed by pyrosequencing. However, this can be time-consuming and expensive; thus, it is unlikely to be widely used by investigators. If the sequences are different, then in theory the melting temperature should be different. Thus, the aim of a recent study was to assess whether high-resolution melt curve analysis can be used to differentiate between MZ twins. Five sets of MZ twins provided buccal swabs that underwent extraction, quantification, bisulfite treatment, polymerase chain reaction amplification and high-resolution melting curve analysis targeting two markers, Alu-E2F3 and Alu-SP. Significant differences were observed between all MZ twins targeting Alu-E2F3 and in four of five MZ twins targeting Alu-SP (P < 0.05). Thus, it has been demonstrated that bisulfite treatment followed by high-resolution melting curve analysis could be used to differentiate between MZ twins.

more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

Engineered E. coli turn into tiny factories for producing new forms of common antibiotic

Engineered E. coli turn into tiny factories for producing new forms of common antibiotic | Amazing Science | Scoop.it

Like a dairy farmer tending to a herd of cows to produce milk, researchers are tending to colonies of the bacteria Escherichia coli (E. coli) to produce new forms of antibiotics — including three that show promise in fighting drug-resistant bacteria. The research, published in the journal Science Advances, was led by Blaine A. Pfeifer, an associate professor of chemical and biological engineering in the University at Buffalo School of Engineering and Applied Sciences. His team included first author Guojian Zhang, Yi Li and Lei Fang, all in the Department of Chemical and Biological Engineering.


For more than a decade, Pfeifer has been studying how to engineer E. coli to generate new varieties of erythromycin, a popular antibiotic. In the new study, he and colleagues report that they have done this successfully, harnessing E. coli to synthesize dozens of new forms of the drug that have a slightly different structure from existing versions.


Three of these new varieties of erythromycin successfully killed bacteria of the species Bacillus subtilis that were resistant to the original form of erythromycin used clinically.


“We’re focused on trying to come up with new antibiotics that can overcome antibiotic resistance, and we see this as an important step forward,” said Pfeifer, PhD.


“We have not only created new analogs of erythromycin, but also developed a platform for using E. coli to produce the drug,” he said. “This opens the door for additional engineering possibilities in the future and it could lead to even more new forms of the drug.”

more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

Nearly indestructible virus yields tool to treat diseases

Nearly indestructible virus yields tool to treat diseases | Amazing Science | Scoop.it

By unlocking the secrets of a bizarre virus that survives in nearly boiling acid, scientists at the University of Virginia School of Medicine have found a blueprint for battling human disease using DNA clad in near-indestructible armor. "What's interesting and unusual is being able to see how proteins and DNA can be put together in a way that's absolutely stable under the harshest conditions imaginable," said Edward H. Egelman, PhD, of the UVA Department of Biochemistry and Molecular Genetics. "We've discovered what appears to be a basic mechanism of resistance - to heat, to desiccation, to ultraviolet radiation. And knowing that, then, we can go in many different directions, including developing ways to package DNA for gene therapy."


The virus SIRV2 belongs to a common crenarchaeal virus family, the Rudiviridae. It was first discovered in 1998 in the hot acidic sulfurous springs of Iceland. According to previous studies, SIRV2 infects Sulfolobus islandicus, a single-celled microorganism that grows optimally at 80 degrees Celsius and at pH 3. The virus has a very stable rod-shaped viral capsule, about 900 nm long and 23 nm in width.


Now, Dr Prangishvili, Dr Egelman and their colleagues have used cryo-electron microscopy to generate a 3D reconstruction of the SIRV2 virion, which revealed a previously unknown form of virion organization.

The team identified surprising similarities between SIRV2 and the spores bacteria form to survive in inhospitable environments.


“Some of these spores are responsible for very, very horrific diseases that are hard to treat, like anthrax. So we show in this study that this virus actually functions in a similar way to some of the proteins present in bacterial spores,” said Dr Egeleman, who is the senior author on the paper published in the journal Science“Understanding how these bacterial spores work gives us potentially new abilities to destroy them,” he said.


Dr Egeleman and co-authors also found that SIRV2 survives the inhospitable conditions by forcing its DNA into what is called A-form, a structural state identified by pioneering DNA researcher Rosalind Franklin more than a half-century ago.


“This is, I think, going to highlight once again the contributions she made, because many people have felt that this A-form of DNA is only found in the laboratory under very non-biological conditions, when DNA is dehydrated or dry. Instead, it appears to be a general mechanism in biology for protecting DNA,” Dr Egelman said.

more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

Mammoth genomes provide recipe for creating Arctic elephants

Mammoth genomes provide recipe for creating Arctic elephants | Amazing Science | Scoop.it
Unlike their elephant cousins, woolly mammoths were creatures of the cold, with long hairy coats, thick layers of fat and small ears that kept heat loss to a minimum. For the first time, scientists have comprehensively catalogued the hundreds of genetic mutations that gave rise to these differences. 

The research reveals how woolly mammoths (Mammuthus primigenius) evolved from the ancestor they share with Asian elephants (Elephas maximus). It could even serve as a recipe for engineering elephants that are able to survive in Siberia.

“These are genes we would need to alter in an elephant genome to create an animal that was mostly an elephant, but actually able to survive somewhere cold,” says Beth Shapiro, an evolutionary geneticist at the University of California, Santa Cruz who was not involved in the latest research. As fanciful as it sounds, such an effort is at a very early stage in a research lab in Boston, Massachusetts.


In the latest study, Vincent Lynch, an evolutionary geneticist at the University of Chicago, Illinois, and his team describe how they sequenced the genomes of three Asian elephants and two woolly mammoths (one died 20,000 years ago, another 60,000 years ago) to a very high quality. They found about 1.4 million DNA letters that differ between mammoths and elephants, which altered the sequence of more than 1,600 protein-coding genes. The study was posted on the biology preprint server bioRxiv.org on 23 April1.


The mammoth genomes also contained extra copies of a gene that controls the production of fat cells and variations in genes linked to insulin signaling, which are in turn linked to diabetes and diabetes prevention. And several of the genes that differ between mammoths and elephants are involved in sensing heat and transmitting that information to the brain.


The team ‘resurrected’ the mammoth version of one of the heat-sensing genes, which encodes a protein called TRPV3 that is expressed in skin and also regulates hair growth. They spliced the gene sequence into the genomes of human cells in the lab and exposed them to different temperatures, revealing that the mammoth TRPV3 protein is less responsive to heat than the elephant version is. The result chimes with a previous finding that mice with a deactivated version of TRPV3 are more likely to spend time in colder parts of their cage compared with normal rodents, and boast wavier hair.


The next step, says Lynch, is to insert the same gene into elephant cells that have been chemically programmed to behave like embryonic cells, and so can be turned into a variety of cell types. Such induced pluripotent stem (iPS) cells could then be used to examine expression of mammoth proteins in different tissues. Lynch's team also plans to test the effects of other mammoth mutations in iPS cells.


Similar work is already being carried out in the lab of George Church, a geneticist at Harvard Medical School in Boston. Using a technology known as CRISPR/Cas9 that allows genes to be easily edited, his team claims to have engineered elephant cells that contain the mammoth version of 14 genes potentially involved in cold tolerance — although the team has not yet tested how this affects the elephant cells. Church plans to do these experiments in “organoids” created from elephant iPS cells.


The work, says Church, is a preamble to editing an entire woolly mammoth genome — and perhaps even resurrecting the woolly mammoth, or at least giving an Asian elephant enough mammoth genes to survive in the Arctic. The second option would be easier to do because it would require fewer mutations than the first option. A 16-square-kilometre reserve in north Siberia, known as Pleistocene Park, has even been proposed as a potential home for such a population of cold-tolerant elephants.


However, whether anyone would want to do such a thing is a different question, says Lynch, and Shapiro agrees. In her book, she outlines the innumerable hurdles that stand in the way of breeding genetically modified ‘woolly elephants’ — from the ethics of applying reproductive technologies to an endangered species to the fact that the field of elephant reproductive biology is still immature.


more...
No comment yet.
Scooped by Dr. Stefan Gruenwald
Scoop.it!

Crime scene discovery – DNA methylation can tell DNA of identical twins apart

Crime scene discovery – DNA methylation can tell DNA of identical twins apart | Amazing Science | Scoop.it

SINCE its first use in the 1980s – a breakthrough dramatised in recent ITV series Code of a Killer– DNA profiling has been a vital tool for forensic investigators.  Now researchers at the University of Huddersfield have solved one of its few limitations by successfully testing a technique for distinguishing between the DNA – or genetic fingerprint – of identical twins.


The probability of a DNA match between two unrelated individuals is about one in a billion.  For two full siblings, the probability drops to one-in-10,000.  But identical twins present exactly the same DNA profile as each other and this has created legal conundrums when it was not possible to tell which of the pair was guilty or innocent of a crime.  This has led to prosecutions being dropped, rather than run the risk of convicting the wrong twin.


Now Dr Graham Williams (pictured right) and his Forensic Genetics Research Group at the University of Huddersfield have developed a solution to the problem and published their findings in the journal Analytical BiochemistryPrevious methods have been proposed for distinguishing the DNA of twins.  One is termed “mutation analysis”, where the whole genome of both twins is sequenced to identify mutations that might have occurred to one of them.


“If such a mutation is identified at a particular location in the twin, then that same particular mutation can be specifically searched for in the crime scene sample.  However, this is very expensive and time-consuming and is unlikely to be paid for by cash-strapped police forces,” according to Dr Williams, who has shown that a cheaper, quicker technique is available.


It is based on the concept of DNA methylation, which is effectively the molecular mechanism that turns various genes on and off. As twins get older, the degree of difference between them grows as they are subjected to increasingly different environments.  For example, one might take up smoking, or one might have a job outdoors and the other a desk job.  This will cause changes in the methylation status of the DNA.


In order to carry our speedy, inexpensive analysis of this, Dr Williams and his team propose a technique named “high resolution melt curve analysis” (HRMA). “What HRMA does is to subject the DNA to increasingly high temperatures until the hydrogen bonds break, known as the melting temperature.  The more hydrogen bonds that are present in the DNA, the higher the temperature required to melt them,” explains Dr Williams.


“Consequently, if one DNA sequence is more methylated than the other, then the melting temperatures of the two samples will differ – a difference that can be measured, and which will establish the difference between two identical twins.”


more...
Taylah Mancey's curator insight, March 24, 2016 3:09 AM

Where i see myself working after completeing my degree, in a lab doing forensic science.

Scooped by Dr. Stefan Gruenwald
Scoop.it!

Chinese scientists admitted to tweaking the genes of human embryos for the first time in history

Chinese scientists admitted to tweaking the genes of human embryos for the first time in history | Amazing Science | Scoop.it

A group of Chinese scientists just reported that they modified the genome of human embryos, something that has never been done in the history of the world, according to a report in Nature News


A recent biotech discovery - one that has been called the biggest biotech discovery of the century - showed how scientists might be able to modify a human genome when that genome was still just in an embryo.


This could change not only the genetic material of a person, but could also change the DNA they pass on, removing "bad" genetic codes (and potentially adding "good" ones) and taking an active hand in evolution.


Concerned scientists published an argument that no one should edit the human genome in this way until we better understood the consequences after a report uncovered rumours that Chinese scientists were already working on using this technology.


But this new paper, published April 18 in the journal Protein and Cell by a Chinese group led by gene-function researcher Junjiu Huang of Sun Yat-sen University, shows that work has already been done, and Nature News spoke to a Chinese source that said at least four different groups are "pursuing gene editing in human embryos."


Specifically, the team tried to modify a gene in a non-viable embryo that would have been responsible for a deadly blood disorder. But they noted in the study that they encountered serious challenges, suggesting there are still significant hurdles before clinical use becomes a reality.


CRISPR, the technology that makes all this possible, can find bad sections of DNA and cut them and even replace them with DNA that doesn't code for deadly diseases, but it can also make unwanted substitutions. Its level of accuracy is still very low.


Huang's group successfully introduced the DNA they wanted in only "a fraction" of the 28 embryos that had been "successfully spliced" (they tried 86 embryos at the start and tested 54 of the 71 that survived the procedure). They also found a "surprising number of ‘off-target’ mutations," according to Nature News.


Huang told Nature News that they stopped then because they knew that if they were do this work medically, that success rate would need to be closer to 100 percent. Our understanding of CRISPR needs to significantly develop before we get there, but this is a new technology that's changing rapidly.


Even though the Chinese team worked with non-viable embryos, embryos that cannot result in a live birth, editing the human genome and changing the DNA of an embryo is considered ethically questionable, because it could lead to more uses of this technology in humans. Changing the DNA of viable embryos could have unpredictable results for future generations, and some researchers want us to understand this better before putting it into practice.


Still, many researchers think this technology (most don't think it's ready to be used yet) could be invaluable. It could eliminate genetic diseases like sickle cell anemia, Huntington's disease, and cystic fibrosis, all devastating illnesses caused by genes that could theoretically be removed. Others fear that once we can do this accurately, it will inevitably be used to create designer humans with specific desired traits. After all, even though this research is considered questionable now, it is still actively being experimented with.


Huang told Nature News that both Nature and Science journals rejected his paper on embryo editing, "in part because of ethical objections." Neither journal commented to Nature News on that statement. Huang plans on trying to improve the accuracy of CRISPR in animal models for now. But CRISPR is reportedly quite easy to use, according to scientists who previously argued against doing this research in embryos now, meaning that it's incredibly likely these experiments will continue.

more...
RegentsCareServices's curator insight, April 25, 2015 10:42 AM

Chinese scientists admitted to tweaking the genes of human embryos for the first time in history

Dorothy R. Cook 's curator insight, October 26, 2017 4:36 AM

They can change the DNA! So is that a way of the child not being able to be found per DNA the child of Its  created by its Mother a and Father by DNA testing because the child original DNA is changed? Has that ever happened and if so by which Scientist. who is the child and parents and why because this was years ago per article therefore things are more advanced and creative now. I does make a person wonder, as DNA is used for other things also, if they can change it in one way why not in and for the others to for the right price or whatever could DNA change have an innocent person found guilty of a crime or a guilty person found innocent of a crime and who would know if it was done? Just saying and asking your opinion on thi s artie including DNA changing , You have say to!

Scooped by Dr. Stefan Gruenwald
Scoop.it!

Scientists use nanoscale building blocks and DNA 'glue' to shape 3-D superlattices

Scientists use nanoscale building blocks and DNA 'glue' to shape 3-D superlattices | Amazing Science | Scoop.it
aking child's play with building blocks to a whole new level-the nanometer scale-scientists at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory have constructed 3D "superlattice" multicomponent nanoparticle arrays where the arrangement of particles is driven by the shape of the tiny building blocks. The method uses linker molecules made of complementary strands of DNA to overcome the blocks' tendency to pack together in a way that would separate differently shaped components. The results, published in Nature Communications, are an important step on the path toward designing predictable composite materials for applications in catalysis, other energy technologies, and medicine. "If we want to take advantage of the promising properties of nanoparticles, we need to be able to reliably incorporate them into larger-scale composite materials for real-world applications," explained Brookhaven physicist Oleg Gang, who led the research at Brookhaven's Center for Functional Nanomaterials (CFN), a DOE Office of Science User Facility.

"Our work describes a new way to fabricate structured composite materials using directional bindings of shaped particles for predictable assembly," said Fang Lu, the lead author of the publication.

The research builds on the team's experience linking nanoparticles together using strands of synthetic DNA. Like the molecule that carries the genetic code of living things, these synthetic strands have complementary bases known by the genetic code letters G, C, T, and A, which bind to one another in only one way (G to C; T to A). Gang has previously used complementary DNA tethers attached to nanoparticles to guide the assembly of a range of arrays and structures. The new work explores particle shape as a means of controlling the directionality of these interactions to achieve long-range order in large-scale assemblies and clusters.

Spherical particles, Gang explained, normally pack together to minimize free volume. DNA linkers-using complementary strands to attract particles, or non-complementary strands to keep particles apart-can alter that packing to some degree to achieve different arrangements. For example, scientists have experimented with placing complementary linker strands in strategic locations on the spheres to get the particles to line up and bind in a particular way. But it's not so easy to make nanospheres with precisely placed linker strands.

"We explored an alternate idea: the introduction of shaped nanoscale 'blocks' decorated with DNA tethers on each facet to control the directional binding of spheres with complementary DNA tethers," Gang said.
more...
No comment yet.