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Scooped by Dr. Stefan Gruenwald!

Researchers Control Embryonic Stem Cells Timing Mechanism With Light

Researchers Control Embryonic Stem Cells Timing Mechanism With Light | Amazing Science |

UC San Francisco researchers have for the first time developed a method to precisely control embryonic stem cell differentiation with beams of light, enabling them to be transformed into neurons in response to a precise external cue.

The technique also revealed an internal timer within stem cells that lets them tune out extraneous biological noise but transform rapidly into mature cells when they detect a consistent, appropriate molecular signal, the authors report in a study published online Aug. 26 in Cell Systems.

“We’ve discovered a basic mechanism the cell uses to decide whether to pay attention to a developmental cue or to ignore it,” said senior author Matthew Thomson, PhD, a researcher in the department of Cellular and Molecular Pharmacology and the Center for Systems and Synthetic Biology at UCSF.

During embryonic development, stem cells perform an elaborately timed dance as they transform from their neutral, undifferentiated form to construct all the major organ systems of the body. Researchers have identified many different molecular cues that signal stem cells when to transform into their mature form, whether it be brain or liver or muscle, at just the right time.

These discoveries have raised hopes that taking control of stem cells could let scientists repair damaged and aging tissues using the body’s own potential for regeneration. But so far, getting stem cells to follow instructions en masse has proven far more difficult than researchers once expected.

“These cells receive so many varied inputs,” said lead author Cameron Sokolik, a Thomson laboratory research assistant at the time of the study. “The question is how does the cell decide when to differentiate?”

To test how stem cells interpret developmental cues as either crucial signals or mere noise, Thomson and colleagues engineered cultured mouse embryonic stem cells in which the researchers could use a pulse of blue light to switch on the Brn2 gene, a potent neural differentiation cue. By adjusting the strength and duration of the light pulses, the researchers could precisely control the Brn2 dosage and watch how the cells respond. They discovered that if the Brn2 signal was strong enough and long enough, stem cells would quickly begin to transform into neurons. But if the signal was too weak or too brief, the cells ignored it completely.

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Scientists Predict that Lab-Grown Burgers will be Available to the Public within Five Years

Scientists Predict that Lab-Grown Burgers will be Available to the Public within Five Years | Amazing Science |

When a team of Dutch scientists unveiled the world’s first stem cell beef burger in 2013, it carried a $300,000 price tag. Worse, it was dry and tasteless. But since the initial lackluster reviews, Mark Post and his colleagues have been hard at work. Now, they say they hope to have a commercially saleable cow-less patty on the market in five years.

Until very recently, lab-grown beef sounded like science fiction. But rapid advances in molecular biology and stem cell technology have placed the futuristic concept within reach. And the arguments for removing animals from the meat equation are practically endless: The meat industry as it exists today swallows an enormous fraction of our land and natural resources, produces vast quantities of greenhouse gases, has contributed to the rise of antibiotic resistant infections, and in many cases, is downright cruel. If test tube burgers can eliminate or diminish even a fraction of these problems, then this seems like one crazy idea worth pursuing.

And pursue it scientists have. In addition to Mark Post’s stem cell burger effort, a team of Israeli researchers under the banner Future Meat are now trying to grow whole chicken breasts in the lab. Meanwhile, efforts to culture fish protein have cropped up intermittently over the years.

Still, five years until we’re slapping ketchup and pickles on artificial meat seems like an awfully fast turnaround for a technology that was at best very nascent two years ago. But Post, who recently founded the company Mosa Meat with the objective of fast-tracking his niche product to mass production, now feels that a five year goal is achievable. As Post told the BBC, the burgers would likely be available as an exclusive, “order on demand” product at first, but “would be on supermarket shelves once a demand had been established and the price comes down.”

While the exact cost of the burgers isn’t yet certain, it’s likely to be competitive. Earlier this year, Post’s team announced that his team had been able to slash the price tag to just a little over $11 per burger, or $36 per pound of cow-less beef. Which is totally comparable to what Western foodies are willing to dish out for a gourmet grass-fed patty at a gastropub these days.

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Scientists Turn Green Algae Into Biofuel at $50 a Barrel

Scientists Turn Green Algae Into Biofuel at $50 a Barrel | Amazing Science |

Scientists have worked out how to cultivate green algae for biofuel in huge quantities at US$50 a barrel, which is about the cost of crude oil. They have even found a way to get electrical energy directly from cyanobacteria or blue-green algae. And they have exploited an alloy that can deliver a colossal pulse of electric power when you kick it.

None of these technologies have advanced beyond the experimental stage, but all are testaments to the ingenuity now being deployed in the world’s laboratories and experimental start-ups.

Fusion power—not to be confused with nuclear fission—exploits the thermonuclear conversion of hydrogen to helium with little or no noxious discharge and the generous release of energy.

This is what powers the sun and fuels the planet’s life. It is also the basis of the thermonuclear bomb. For the last 60 years, humans have been trying to make fusion work peacefully on Earth, with only tantalizing flickers of success.

But if it does work, British scientists report in the journal Fusion Engineering and Design, it will not be too expensive. They analyzed the cost of building, running and ultimately decommissioning a fusion power station and found it comparable to fission or nuclear energy.

The challenge of nuclear fusion is to heat stripped-down heavy hydrogen atoms to 100 million Celsius so that they fuse into helium, while finding a way to tap the released energy and at the same time keep the reaction going.

The International Thermonuclear Experimental Reactor, now being built in the South of France, might in a decade show that it could happen. Assuming it works, the process should be affordable. There would be no high-level radioactive waste, no problems with finding fuel and no by-product that could be turned into nuclear weaponry.

“Obviously we have had to make assumptions, but what we can say is that our predictions suggest fusion won’t be vastly more expensive than fission,” said Damian Hampshire, of the Center for Materials Physics at Durham University, UK.

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Chinese Researchers Knock Out Myostatin Gene in Beagles with CRISPR, Generating First Gene-Edited Dogs

Chinese Researchers Knock Out Myostatin Gene in Beagles with CRISPR, Generating First Gene-Edited Dogs | Amazing Science |

Man’s best friend is now his newest genetic engineering project.

Scientists in China say they are the first to use gene editing to produce customized dogs. They created a beagle with double the amount of muscle mass by deleting a gene called myostatin.

The dogs have “more muscles and are expected to have stronger running ability, which is good for hunting, police (military) applications,” Liangxue Lai, a researcher with the Key Laboratory of Regenerative Biology at the Guangzhou Institutes of Biomedicine and Health, said in an e-mail.

Lai and 28 colleagues reported their results last week in the Journal of Molecular Cell Biology, saying they intend to create dogs with other DNA mutations, including ones that mimic human diseases such as Parkinson’s and muscular dystrophy, in order to test drugs and other treatments. “The goal of the research is to explore an approach to the generation of new disease dog models for biomedical research,” says Lai. “Dogs are very close to humans in terms of metabolic, physiological, and anatomical characteristics.”

Lai said his group had no plans breed to breed the ultra-muscular beagles as pets. Other teams, however, could move quickly to commercialize gene-altered dogs, potentially editing their DNA to change their size, enhance their intelligence, or correct genetic illnesses. A different Chinese Institute, BGI, said in September it had begun selling miniature pigs, created via gene editing, for $1,600 each as novelty pets.

The Chinese beagle project was led by Lai and Gao Xiang, a specialist in genetic engineering of mice at Nanjing University. The dogs are being kept at the Guangzhou General Pharmaceutical Research Institute, which says on its website that it breeds more than 2,000 beagles a year for research. Beagles are commonly used in biomedical research in both China and the U.S.

Genome editing refers to newly developed techniques that let scientists easily disable genes or rearrange their DNA letters. The method used to change the beagles, known as CRISPR-Cas9, is particularly inexpensive and precise (see “10 Breakthrough Technologies 2014: Genome Editing”).

Last month, Duanqing Pei, a representative of the Chinese Academy of Sciences, highlighted Lai’s work as part of what he called a large Chinese effort to modify animals using CRISPR. The list of animals already engineered using gene editing in China includes goats, rabbits, rats, and monkeys. Pei described the efforts as a national scientific priority and part of China’s effort to establish world-class research.

The ease with which gene-editing can be carried out has raised worries that humans could be next (see “Engineering the Perfect Baby”). Those fears were stoked in April when another Chinese team reported altering human embryos in the laboratory in an attempt to correct a genetic defect called beta-thalassemia (see “Chinese Team Reports Gene-Editing Human Embryos”).

Dr. Stefan Gruenwald's insight:

Jill MacKay Retweeted Dr. Stefan Gruenwald

Misleading photo that's a whippet where double muscling occurs. Story abt beagles interesting though! @arjantolkamp                                  

Response: Correct! The whippet was the first dog for which a myostatin deficiency was seen. See here

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Investigators create complex kidney structures from adult human stem cells

Investigators create complex kidney structures from adult human stem cells | Amazing Science |
Investigators at Brigham and Women's Hospital (BWH) and the Harvard Stem Cell Institute (HSCI) have established a highly efficient method for making kidney structures from stem cells that are derived from skin taken from patients. The kidney structures formed could be used to study abnormalities of kidney development, chronic kidney disease, the effects of toxic drugs, and be incorporated into bioengineered devices to treat patients with acute and chronic kidney injury. In the longer term, these methods could hasten progress toward replacing a damaged or diseased kidney with tissue derived from a patient's own cells. These results were published in Nature Biotechnology this week.

"Kidneys are the most commonly transplanted organs, but demand far outweighs supply," said co-corresponding author Ryuji Morizane, MD, PhD, associate biologist in BWH's Renal Division. "We have converted skin cells to stem cells and developed a highly efficient process to convert these stem cells into kidney structures that resemble those found in a normal human kidney. We're hopeful that this finding will pave the way for the future creation of kidney tissues that could function in a patient and eliminate the need for transplantation from a donor."

Chronic kidney disease (CKD) affects 9 to11 percent of the U.S. adult population and is a serious public health problem worldwide. Central to the progression of CKD is the gradual and irreversible loss of nephrons, the individual functional units of the kidney. Patients with end-stage kidney disease benefit from treatments such as dialysis and kidney transplantation, but these approaches have several limitations, including the limited supply of compatible organ donors.

While the human kidney does have some capacity to repair itself after injury, it is not able to regenerate new nephrons. In previous studies, researchers have successfully differentiated stem cells into heart, liver, pancreas or nerve cells by adding certain chemicals, but kidney cells have proved challenging. Using normal kidney development as a roadmap, the BWH investigators developed an efficient method to create kidney precursor cells that self assemble into structures which mimic complex structures of the kidney. The research team further tested these organoids - three-dimensional organ structures grown in the lab - and found that they could be used to model kidney development and susceptibility of the kidney tissue to therapeutic drug toxicity. The kidney structures also have the potential to facilitate further studies of how abnormalities occur as the human kidney develops in the uterus and to establish models of disease where they can be used to test new therapies.
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Where in the world could the first CRISPR-CAS baby be born?

Where in the world could the first CRISPR-CAS baby be born? | Amazing Science |
They are meeting in China; they are meeting in the United Kingdom; and they met in the United States last week. Around the world, scientists are gathering to discuss the promise and perils of editing the genome of a human embryo. Should it be allowed — and if so, under what circumstances?

The meetings have been prompted by an explosion of interest in the powerful technology known as CRISPR/Cas9, which has brought unprecedented ease and precision to genetic engineering. This tool, and others like it, could be used to manipulate the DNA of embryos in a dish to learn about the earliest stages of human development. In theory, genome editing could also be used to 'fix' the mutations responsible for heritable human diseases. If done in embryos, this could prevent such diseases from being passed on.

The prospects have prompted widespread concern and discussion among scientists, ethicists and patients. Fears loom that if genome editing becomes acceptable in the clinic to stave off disease, it will inevitably come to be used to introduce, enhance or eliminate traits for non-medical reasons. Ethicists are concerned that unequal access to such technologies could lead to genetic classism. And targeted changes to a person's genome would be passed on for generations, through the germ line (sperm and eggs), fueling fears that embryo editing could have lasting, unintended consequences. Adding to these concerns, the regulations in many countries have not kept pace with the science.

The journal Nature has tried to capture a snapshot of the legal landscape by querying experts and government agencies in 12 countries with histories of well-funded biological research. The responses reveal a wide range of approaches. In some countries, experimenting with human embryos at all would be a criminal offense, whereas in others, almost anything would be permissible.

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Forget GMO fear: DuPont Predicts CRISPR GMO Plants on Dinner Plates in 5 Years

Forget GMO fear: DuPont Predicts CRISPR GMO Plants on Dinner Plates in 5 Years | Amazing Science |

Agricultural biotech giants are starting to make moves into CRISPR gene editing, saying they’ll be selling seeds engineered with the technology by the end of this decade.

DuPont said today it entered an agreement with Caribou Biosciences, a spin-off from the laboratory of Jennifer Doudna at the University of California, Berkeley, who carried out key work on CRISPR-Cas9, a technology that provides something like a find-and-replace feature for DNA.

DuPont says it is already growing corn and wheat plants edited with CRISPR in greenhouses and that field trials will start next spring.

“We are talking about bringing products to market in five to 10 years,” says Neal Gutterson, vice president for agricultural biotechnology at Pioneer Hi-Bred, part of DuPont’s $11-billion-per-year crop chemicals and biotech seed business. “That is a pretty damn good time line compared to other technology.”

DuPont is testing CRISPR to make drought-resistant corn as well as wheat genetically altered so it will breed like a hybrid, rather than self-pollinate as it typically does. Hybrid plants are vigorous, and yields can jump by 10 or 15 percent.

A growing list of plant types have already been genetically engineered with CRISPR-Cas9 in academic laboratories, including soybeans, rice, and potatoes. Last month, a Japanese team used gene editing to turn off fruit-ripening genes in tomato plants.

As part of their collaboration, DuPont said it had made an investment in Caribou, a small startup that holds commercial rights to patents Berkeley has applied for on CRISPR-Cas9. DuPont will have exclusive rights to those patents in crops like corn and soybeans, should they be approved.

Currently, most GMOs are transgenic plants that have been engineered by adding bacterial genes to the plants so that they poison insects or survive weed sprays. Thanks to biotechnology, the seed business has ballooned to about $40 billion a year, and companies like Monsanto, Dow, DuPont, and Syngenta have come to dominate it. But the need to invest millions more in a sweeping technology shift hits as depressed commodity markets have made the profitability of biotech seeds less certain.

Gutterson says DuPont thinks gene editing will kick off a new wave of products and profits. “We have no doubt that genome editing is going to have a material impact on the value proposition,” he says. “We think another whole cycle could come from genome editing.”

Gene editing could lead to some surprising creations in agriculture. For instance, peanuts have a number of proteins responsible for allergies. Getting rid of them is challenging, but allergy-free peanuts might be possible with the new technology.

Christian Faltado Cantos's curator insight, October 18, 2015 11:25 PM

Gene editing could lead to some surprising creations in agriculture.

Ines Jurisic's curator insight, October 19, 2015 7:48 AM

."..Thanks to biotechnology, the seed business has ballooned to about $40 billion a year, and companies like Monsanto, Dow, DuPont, and Syngenta have come to dominate it." -----------In Money we Trust:( 

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CRISPR-CAS Could Generate a Hypoallergenic Peanut But Anti-GMO Fear Gets In Its Way

CRISPR-CAS Could Generate a Hypoallergenic Peanut But Anti-GMO Fear Gets In Its Way | Amazing Science |

Anyone with a child in school is probably aware of the need for peanut free zones. You get a notice when your child returns from school on the first day stating that at least one child in their class has a peanut allergy, which means nothing with peanuts gets sent to school for your child’s lunch. If you are a parent of a child with a peanut allergy you understand how important and serious this is – your child is literally one errant Snickers bar away from death.

The general consensus is that food allergies have been on the rise in developed countries, although studies show a wide range of estimates based upon study techniques. A US review found the prevalence of self-reported peanut allergies ranged from 0-2%. A European review found the average estimate to be 2.2% – around 2% is usually the figure quoted. In a direct challenge study, at age 4, 1.1% of the 1218 children were sensitized to peanuts, and 0.5% had had an allergic reaction to peanuts. That means there are millions of people with peanut allergies.

So far there is no cure for the allergies themselves. Acute attacks can be treated with epinephrine, but there are cases of children dying (through anaphylaxis) even after multiple shots. The only real treatment is to obsessively avoid contact with the food in question. Peanuts, tree nuts, and shellfish are the good most likely to cause anaphylaxis.

There is, however, a potential solution. Researchers have been working for year on developing a cultivar of peanut that does not cause allergies. Attempts to achieve this through conventional breeding and hybridization have failed and does not seem likely to succeed. The only real hope of a hypoallergenic peanut is through genetic modification. We are, in fact, on the brink of achieving this goal, but anti-GMO fears are getting in the way.

There are 7 proteins that have been identified in peanuts that cause an allergic reaction. The allergic reaction from peanuts is entirely an IgE mediated Type I hypersensitivity response. The proteins crosslink with the IgE antibodies, which them bind to mast cells and basophils (cells in the immune system) causing a significant inflammatory response that clinically causes the allergic reaction. One peanut contains about 200mg of protein, and as little as 2mg is enough to cause objective symptoms of an allergic reaction.

What makes a food protein an allergen is interesting. About 700 amino acid sequences have been identified that help confer allergenicity to protein. These protein segments allow the protein to survive processing and digestion, and allow the protein to bind to IgE antibodies.

In 2005 a study was published showing that it is possible to silence the gene for the Ara H2 protein, the primary allergenic protein in peanuts. A 2008 follow up by the same team showed decreased allergenicity of the altered peanut. So where are our hypoallergenic peanuts? This is a complicated question, and I don’t think I can give a full answer.

The delay in marketing a hypoallergenic peanut seems to be due partly to technical issues – it turns out to be a lot more difficult to make the necessary changes than at first thought. However, it also seems to be due to the anti-GMO campaign, which has been scaring away investors and making politicians gun-shy.

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How To Detect ANY Virus In A Patient's Blood

How To Detect ANY Virus In A Patient's Blood | Amazing Science |

Better diagnosis leads to better treatment – that’s well-known. Easier said than done, of course, since that’s not always possible when tests for diseases or infections take time to generate results, for example, or are inaccurate or insensitive. Take viruses: There is an abundance out there capable of causing disease, many of which can present similar symptoms or, perhaps worse, none at all. Detection can, therefore, be a bit of a nightmare, sometimes demanding a labor-intensive and costly suite of tests to get to the bottom of a case.

What if there was a universal, one-size-fits-all-test that could pick up any known virus in a sample, eliminating this time-consuming detective work? That might sound quite out of our clutches, but researchers at Washington University School of Medicine might just have achieved this long-awaited, eyebrow-raising feat.

“With this test, you don’t have to know what you’re looking for,” senior author Gregory Storch said in a statement. “It casts a broad net and can efficiently detect viruses that are present at very low levels. We think the test will be especially useful in situations where a diagnosis remains elusive after standard testing or in situations in which the cause of a disease outbreak is unknown.”

Describing their work in Genome Research, the results are pretty impressive. To make their “ViroCap,” the researchers began by creating a broad panel of sequences to be targeted by the test, which they generated using unique stretches of DNA or RNA found in viruses across 34 different human- and animal-infecting families. This resulted in millions of stretches of nucleic acid that can be used to capture matching strands in a sample, should they be present.

But the broad spectrum of this test is not its only remarkable quality: It’s so sensitive that it can even pick up slight variations in sequences, meaning that a virus’ subtype can also be identified – a feature not possible with many traditional tests. Although that wouldn’t necessarily change the way a patient is treated, it could aid disease surveillance.

To demonstrate its capabilities, the researchers took samples from a small group of patients at St. Louis Children’s Hospital and compared the results to those obtained from standard tests. While traditional sequencing managed to find viruses in the majority of the children, ViroCap also managed to pick up some common viruses that it had failed to detect. These included a flu virus and the virus responsible for chickenpox. In a second test run on a different group of children displaying fevers, the new test found an additional seven viruses to the 11 that the traditional testing managed to detect.  

All of this sounds great on paper, but of course it is not yet ready to be used in the clinic. Further trials are required first to check its accuracy on larger groups of people, as so far only a limited number of patients have been screened. But when the time comes, the team plans to make it widely available, which would be welcome in the face of outbreaks like Ebola. Furthermore, the team ultimately hopes to tweak it so that it can detect genetic material from other microbes, like bacteria. If that’s possible, we could have a seriously useful machine on our hands that could change diagnostic medicine for the better. 

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Team succeeds in producing photoreceptors from human embryonic stem cells

Team succeeds in producing photoreceptors from human embryonic stem cells | Amazing Science |

Age-related macular degeneration (AMRD) could be treated by transplanting photoreceptors produced by the directed differentiation of stem cells, thanks to findings published today by Professor Gilbert Bernier of the University of Montreal and its affiliated Maisonneuve-Rosemont Hospital. ARMD is a common eye problem caused by the loss of cones. Bernier's team has developed a highly effective in vitro technique for producing light sensitive retina cells from human embryonic stem cells. "Our method has the capacity to differentiate 80% of the stem cells into pure cones," Professor Gilbert explained. "Within 45 days, the cones that we allowed to grow towards confluence spontaneously formed organised retinal tissue that was 150 microns thick. This has never been achieved before."

In order to verify the technique, Bernier injected clusters of retinal cells into the eyes of healthy mice. The transplanted photoreceptors migrated naturally within the retina of their host. "Cone transplant represents a therapeutic solution for retinal pathologies caused by the degeneration of photoreceptor cells," Bernier explained. "To date, it has been difficult to obtain great quantities of human cones." His discovery offers a way to overcome this problem, offering hope that treatments may be developed for currently non-curable degenerative diseases, like Stargardt disease and ARMD. "Researchers have been trying to achieve this kind of trial for years," he said. "Thanks to our simple and effective approach, any laboratory in the world will now be able to create masses of photoreceptors. Even if there's a long way to go before launching clinical trials, this means, in theory, that will be eventually be able to treat countless patients."

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Alternative CRISPR system could improve genome editing, make it simpler and more exact

Alternative CRISPR system could improve genome editing, make it simpler and more exact | Amazing Science |

The CRISPR/Cas9 technique is revolutionizing genetic research: Scientists have already used it to engineer crops, livestock andeven human embryos, and it may one day yield new ways to treat disease.

But now one of the technique's pioneers thinks that he has found a way to make CRISPR even simpler and more precise. In a paper published in Cell on 25 September, a team led by synthetic biologist Feng Zhang of the Broad Institute in Cambridge, Massachusetts, reports the discovery of a protein1 called Cpf1 that may overcome one of CRISPR-Cas9’s few limitations; although the system works well for disabling genes, it is often difficult to truly edit them by replacing one DNA sequence with another.

The CRISPR/Cas9 system evolved as a way for bacteria and archaea to defend themselves against invading viruses. It is found in a wide range of these organisms, and uses an enzyme called Cas9 to cut DNA at a site specified by 'guide' strands of RNA. Researchers have turned CRISPR/Cas9 into a molecular-biology powerhouse that can be used in other organisms. The cuts made by the enzyme are repaired by the cell’s natural DNA-repair processes.

CRISPR is much simpler than previous gene-editing methods, but Zhang thought there was still room for improvement. So he and his colleagues searched the bacterial kingdom to find an alternative to the Cas9 enzyme commonly used in laboratories. In April, they reported that they had discovered a smaller version of Cas9 in the bacterium Staphylococcus aureus2. The small size makes the enzyme easier to shuttle into mature cells — a crucial destination for some potential therapies. The team was also intrigued by Cpf1, a protein that looks very different from Cas9, but is present in some bacteria with CRISPR. The scientists evaluated Cpf1 enzymes from 16 different bacteria, eventually finding two that could cut human DNA.

They also uncovered some curious differences between how Cpf1 and Cas9 work. Cas9 requires two RNA molecules to cut DNA; Cpf1 needs only one. The proteins also cut DNA at different places, offering researchers more options when selecting a site to edit. “This opens up a lot of possibilities for all the things we could not target before,” says epigeneticist Luca Magnani of Imperial College London.

Cpf1 also cuts DNA in a different way. Cas9 cuts both strands in a DNA molecule at the same position, leaving behind what molecular biologists call ‘blunt’ ends. But Cpf1 leaves one strand longer than the other, creating a 'sticky' end. Blunt ends are not as easy to work with: a DNA sequence could be inserted in either end, for example, whereas a sticky end will only pair with a complementary sticky end. “The sticky ends carry information that can direct the insertion of the DNA,” says Zhang. “It makes the insertion much more controllable.”

Zhang’s team is now working to use these sticky ends to improve the frequency with which researchers can replace a natural DNA sequence. Cuts left by Cas9 tend to be repaired by sticking the two ends back together, in a relatively sloppy repair process that can leave errors. Although it is possible that the cell will instead insert a designated, new sequence at that site, that kind of repair occurs at a much lower frequency. Zhang hopes that the unique properties of how Cpf1 cuts may be harnessed to make such insertions more frequent.

For Bing Yang, a plant biologist at the Iowa State University in Ames, this is the most exciting aspect of Cpf1. “Boosting the efficiency would be a big step for plant science,” he says. “Right now, it is a major challenge.”

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Protein-based sensor could detect viral infection or kill cancer cells

Protein-based sensor could detect viral infection or kill cancer cells | Amazing Science |

MIT biological engineers have developed a modular system of proteins that can detect a particular DNA sequence in a cell and then trigger a specific response, such as cell death. This system can be customized to detect any DNA sequence in a mammalian cell and then trigger a desired response, including killing cancer cells or cells infected with a virus, the researchers say.

“There is a range of applications for which this could be important,” says James Collins, the Termeer Professor of Medical Engineering and Science in MIT’s Department of Biological Engineering and Institute of Medical Engineering and Science (IMES). “This allows you to readily design constructs that enable a programmed cell to both detect DNA and act on that detection, with a report system and/or a respond system.”

Collins is the senior author of a Sept. 21 Nature Methods paper describing the technology, which is based on a type of DNA-binding proteins known as zinc fingers. These proteins can be designed to recognize any DNA sequence. “The technologies are out there to engineer proteins to bind to virtually any DNA sequence that you want,” says Shimyn Slomovic, an IMES postdoc and the paper’s lead author. “This is used in many ways, but not so much for detection. We felt that there was a lot of potential in harnessing this designable DNA-binding technology for detection.”

Via Integrated DNA Technologies
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UK scientists seek permission to genetically modify human embryos with CRISPR-CAS

UK scientists seek permission to genetically modify human embryos with CRISPR-CAS | Amazing Science |

Researchers apply for licence months after Chinese team become first to announce they have altered DNA.  Scientists in Britain have applied for permission to genetically modify human embryos as part of a research project into the earliest stages of human development.

The work marks a controversial first for the UK and comes only months after Chinese researchers became the only team in the world to announce they had altered the DNA of human embryos. Kathy Niakan, a stem cell scientist at the Francis Crick Institute in London, has asked the government’s fertility regulator for a licence to perform so-called genome editing on human embryos. The research could see the first genetically modified embryos in Britain created within months.

Donated by couples with a surplus after IVF treatment, the embryos would be used for basic research only. They cannot legally be studied for more than two weeks or implanted into women to achieve a pregnancy.

Though the modified embryos will never become children, the move will concern some who have called for a global moratorium on the genetic manipulation of embryos, even for research purposes. They fear a public backlash could derail less controversial uses of genome editing, which could lead to radical new treatments for disease.

Niakan wants to use the procedure to find genes at play in the first few days of human fertilization, when an embryo develops a coating of cells that later form the placenta. The basic research could help scientists understand why some women lose their babies before term.

The Human Fertilisation and Embryology Authority (HFEA) has yet to review her application, but is expected to grant a licence under existing laws that permit experiments on embryos provided they are destroyed within 14 days. In Britain, research on embryos can only go ahead under a licence from an HFEA panel that deems the experiments to be justified.

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Genetically engineered mosquito larva glow in different colors depending on which mutations they carry

Genetically engineered mosquito larva glow in different colors depending on which mutations they carry | Amazing Science |

Genetically altered Aedes aegypti mosquitos developed by the biotech firm Oxitec carry a lethal gene that prevents their female offspring from maturing. The company hopes to limit the spread of mosquito-borne diseases such as Chikungunya virus and Dengue fever by releasing engineered mosquitos that will produce inviable offspring and shrink the population. Oxitec has already conducted field trials in Malaysia and on the Caribbean island of Grand Cayman. It’s now planning a trial in the Florida Keys.

Genetically altered insects are usually regulated by the USDA’s Animal and Plant Health Inspection Service (APHIS) because they are intended to control plant pests. But these mosquitos aren’t plant pests; they are a new strategy to prevent human disease, leading some to argue that they should be treated like other anti-infective medications and reviewed as a new drug by FDA’s Center for Drug Evaluation and Research (CDER).

The Oxitec mosquito was instead deemed a “new animal drug,” and is being evaluated by another FDA office, the Center for Veterinary Medicine. It is the same office that evaluates other technologies to sterilize animals for population control. The decision has prompted concerns that the FDA office is less equipped than USDA to carry out an assessment of the mosquito’s environmental impact. (Meanwhile the company’s new genetically modified diamondback moth, which uses the same basic strategy but targets a scourge on vegetable crops, has been evaluated and cleared for field trials by USDA.)

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Scientists produce clearest-ever images of subunits of telomerase

Scientists produce clearest-ever images of subunits of telomerase | Amazing Science |

Scientists from UCLA and UC Berkeley have produced images of telomerase in much higher resolution than ever before, giving them major new insights about the enzyme. Their findings, published online today by the journal Science, could ultimately lead to new directions for treating cancer and preventing premature aging.

"Many details we could only guess at before, we can now see unambiguously, and we now have an understanding of where the different components of telomerase interact," said Juli Feigon, a professor of chemistry and biochemistry in the UCLA College and a senior author of the study. "If telomerase were a cat, before we could see its general outline and the location of the limbs, but now we can see the eyes, the whiskers, the tail and the toes."

The research brought together experts in structural biology, biochemistry and biophysics, and a wide range of cutting-edge research techniques.

Telomerase's primary job is to maintain the DNA in telomeres, the structures at the ends of our chromosomes that act like the plastic tips at the ends of shoelaces. When telomerase isn't active, each time our cells divide, the telomeres get shorter. When that happens, the telomeres eventually become so short that the cells stop dividing or die.

On the other hand, cells with abnormally active telomerase can constantly rebuild their protective chromosomal caps and become immortal. Making cells immortal might sound like a promising prospect, but it actually is harmful because DNA errors accumulate over time, which damages cells, said Feigon, who also is a researcher at UCLA's Molecular Biology Institute and an associate member of the UCLA-Department of Energy Institute of Genomics and Proteomics.

Telomerase is particularly active in cancer cells, which helps make them immortal and enables cancer to grow and spread. Scientists believe that controlling the length of telomeres in cancer cells could be a way to prevent them from multiplying.

More info about telomeres, telomerase and disease can be found here.

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The Center for Genome Architecture: Changing the Way DNA folds

The Center for Genome Architecture: Changing the Way DNA folds | Amazing Science |

A multi-institutional team spanning Baylor College of Medicine, Rice UniversityStanford University, and the Broad Institute of MIT and Harvard has reported the first successful genome surgery, changing how the genome is folded inside the nucleus. The advance may lead to new methods of understanding and overcoming genetic diseases.

Last year, researchers at Baylor College of Medicine’s Center for Genome Architecture demonstrated that when the 2-meter long human genome folds up inside the nucleus of a cell, it forms roughly 10,000 loops. These loops turn genes on and off, and control how long stretches of the genome are packed. Anomalies in this folding process can lead to disease. The team also discovered a DNA codeword, or “motif,” that lies at both ends of nearly all loops: a string of fewer than 20 genetic letters that causes the DNA to bind a protein called CTCF. More often than not, these motifs lie in what had previously been thought of as “junk” DNA.

Now, in a result with profound consequences for genetic research, a team at the Center, which is directed by Dr. Erez Lieberman Aiden, has demonstrated that by manipulating these motifs, it is possible to destroy, move, and create new loops in the genome. The work, led by co-first authors Adrian Sanborn and Suhas Rao, both graduate students in the Aiden lab and at Stanford University, appears this week in the journal Proceedings of the National Academy of Sciences.

“We were able to use our insights into how loops form in nature in order to engineer genome loops artificially. This means that it is possible, at least in principle, to fix errors in genome folding by modifying a handful of genetic letters, without disturbing the surrounding DNA,” said Aiden, senior author on the new study, as well as a McNair Scholar at Baylor and a Senior Investigator at Rice University’s Center for Theoretical Biological Physics.

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Fine Screen of Essential Genes in the Human Genome

Fine Screen of Essential Genes in the Human Genome | Amazing Science |

For the first time, a comprehensive set of cell-essential genes in the human genome has been compiled. This feat, which not only points to deeper studies of human genetics but also suggests a strategy for finding vulnerabilities in cancer cells, was achieved thanks to the CRISPR-Cas9 gene-editing system. This system proved sufficiently rigorous to succeed where other gene-knockout approaches, such as RNA interference, had failed, mainly due to off-target effects and incomplete gene silencing.

Using CRISPR-Cas9, scientists at the Whitehead Institute and the Broad Institute constructed a genome-wide single-guide RNA (sgRNA) library to screen for genes required for proliferation and survival in a human cancer cell line. The sgRNA library targeted slightly more than 18,000 genes, of which approximately 10% proved to be essential.

These results appeared October 15, 2015, in the journal Science, in an article entitled, “Identification and characterization of essential genes in the human genome.” The article describes how the results obtained with the CRISPR-Cas9 approach were validated by another approach, gene-trap mutagenesis, which involved screening for essential genes in a unique line of haploid human cells.

The set of essential genes identified in the current study largely consists of genes that encode components of fundamental pathways, are expressed at high levels, and contain few inactivating polymorphisms in the human population. For example, the genes associated with fundamental pathways include many that participate in DNA replication, RNA transcription, and translation of messenger RNA.

Of the essential genes found to be involved in RNA processing, about 300 were previously uncharacterized. Moreover, the products of these genes were determined to be largely localized to the nucleolus.

Additional findings pertain specifically to cancer. “[Our screens],” the authors indicated in the Science article, “revealed differences specific to each cell line and cancer type that reflect the developmental origin, oncogenic drivers, paralogous gene expression pattern, and chromosomal structure of each line.”

This work, which was led by Whitehead Member David Sabatini and Broad Institute Director Eric Lander, used the CRISPR-Cas9 approach to investigate cell lines derived from two cancers, chronic myelogenous leukemia (CML) and Burkitt's lymphoma. The novel method not only identified the essentiality of the known genes—in the case of CML, it hit on the BCR and ABL1 genes, whose translocation is the target of the successful drug Gleevec—but also highlighted additional genes that may be therapeutic targets in these cancers.

"The ability to zero in on the essential genes in the highly complex human system will give us new insight into how diseases, such as cancer, continue to resist efforts to defeat them," said Dr. Lander.

"This is really the first time we can reliably, accurately, and systematically study genetics in mammalian cells," added Dr. Sabatini. "It's remarkable how well it's working."

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CRISPR tweak may help gene-edited crops bypass biosafety regulation

CRISPR tweak may help gene-edited crops bypass biosafety regulation | Amazing Science |

A twist on a revolutionary gene-editing technique may make it possible to modify plant genomes while sidestepping national biosafety regulations, South Korean researchers say.

Plant scientists have been quick to experiment with the popular CRISPR/Cas9 technique, which uses an enzyme called Cas9, guided by two RNA strands, to precisely cut segments of DNA in a genome. By disabling specific genes in wheat and rice, for example, researchers hope to make disease-resistant strains of the crops.

But the process can introduce bits of foreign DNA into plant genomes. And some jurisdictions, such as the European Union, could decide to classify such plants as genetically modified organisms (GMOs)1 — making their acceptance by regulatory bodies contentious, says geneticist Jin-Soo Kim of Seoul National University.

Kim and his team tweaked the technique so that it can delete specific plant genes without introducing foreign DNA, creating plants that he and his colleagues think “might be exempt from current GMO regulations”2.

“In terms of science, our approach is just another improvement in the field of genome editing. However, in terms of regulations and public acceptance, our method could be path-breaking,” says Kim.

Conventionally, researchers get CRISPR/Cas9 working in a plant cell by first shuttling in the gene that codes for the Cas9 enzyme. The gene is introduced on a plasmid — a circular packet of DNA — which is usually carried into a plant by the bacterial pest Agrobacterium tumefaciens. As a result, Agrobacterium DNA can end up in the plant’s genome. Even if the pest is not used, fragments of the Cas9 gene may themselves be incorporated into the plant's genome.

To get around this problem, Kim and his colleagues avoid gene-shuttling altogether. They report a recipe to assemble the Cas9 enzyme together with its guide RNA sequences (which the enzyme requires to find its target) outside the plant, and use solvents to get the resulting protein complex into the plant. The technique works efficiently to knock out selected genes in tobacco plants, rice, lettuce and thale cress, they say, reporting their results in Nature Biotechnology2.

“I think this is a milestone work for plant science,’ says bioethicist Tetsuya Ishii at Hokkaido University in Sapporo, Japan, who has extensively studied the framework of regulation surrounding genetic engineering in plants.

Kim wants to use the technique to edit the banana; the crop's most popular cultivar, the Cavendish variety, is struggling to combat a devastating soil fungus and may go extinct. Gene editing could, for example, be used to knock out the receptor that the fungus uses to invade cells, without any need, in Kim’s view, to classify the resulting banana as a GMO. “We will save the banana so that our children and grandchildren can still enjoy the fruit,” he says.

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Single point mutation is sufficient to switch preference of GLUT5 from fructose to glucose

Single point mutation is sufficient to switch preference of GLUT5 from fructose to glucose | Amazing Science |

The altered activity of the fructose transporter GLUT5, an isoform of the facilitated-diffusion glucose transporter family, has been linked to disorders such as type 2 diabetes and obesity. GLUT5 is also overexpressed in certain tumor cells, and inhibitors are potential drugs for these conditions. Here we describe the crystal structures of GLUT5 from Rattus norvegicus and Bos taurus in open outward- and open inward-facing conformations, respectively. GLUT5 has a major facilitator superfamily fold like other homologous monosaccharide transporters. On the basis of a comparison of the inward-facing structures of GLUT5 and human GLUT1, a ubiquitous glucose transporter, we show that a single point mutation is enough to switch the substrate-binding preference of GLUT5 from fructose to glucose. A comparison of the substrate-free structures of GLUT5 with occluded substrate-bound structures of Escherichia coli XylE suggests that, in addition to global rocker-switch-like re-orientation of the bundles, local asymmetric rearrangements of carboxy-terminal transmembrane bundle helices TM7 and TM10 underlie a ‘gated-pore’ transport mechanism in such monosaccharide transporters.

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Genome Sequencing Is Becoming Less Ambiguous and More Clinically Relevant

Genome Sequencing Is Becoming Less Ambiguous and More Clinically Relevant | Amazing Science |

When people talk about the $1,000 genome, they are not speaking about the whole genome, but the exons, the so-called coding regions of the genome. “Six years ago, I was spending $15,000 per exome sequence,” says Gholson Lyon, M.D., Ph.D., a genomic scientist working for the Cold Spring Harbor Laboratory. “Now that costs about $700.”

Whole genome sequencing is more expensive. “We are still not at the $1,000 genome in my opinion,” Dr. Lyon continues. “Almost everyone I’ve talked to is charging $1,500–2,000, and we pay $3,000 because that gets us 60× coverage of the genome, which we have shown is very important to recover small insertions and deletions in the genome ranging in size from 5 to 50 base pairs.”

Dr. Lyon, who studies rare but heritable medical diseases such as Ogden syndrome and TAF1 syndrome, believes that advances in next-generation sequencing technology—better software algorithms, improved methodologies, and lower costs—accelerate his work and the work of others conducting clinical research.

The standard advocated by Illumina, the industry giant, and other sequencing companies is a 30× genome, which means sequencing the genome enough to generate on average 30 reads aligned at each base pair. But according to Dr. Lyon, the 30× genome does not capture all the insertions and deletions.

Illumina technology works by providing high-throughput short-read sequencing. This approach is optimized for detecting single-nucleotide polymorphisms commonly referred to as single nucleotide polymorphisms.

“Illumina has focused on the throughput,” says Jonas Korlach, Ph.D., CSO of PacBio. He contends that this focus “came at a price of having short read lengths, bias with respect to GC content, and sequence complexity that no longer allows you to sequence all of the DNA that is part of your genome.” Therefore, Dr. Korlach continues, “we wanted to build something that gives you the best performance in all four areas that are relevant to the performance of sequencing.”

Pacific Biosciences’ SMRT DNA sequencing is performed on SMRT Cells, nanofabricated consumable substrates that come in an “8Pac” format. Each SMRT Cell is patterned with 150,000 zero-mode waveguide (ZMW) light-detection volumes. Single polymerases are immobilized in the ZMWs, which are open at the top to diffusing phospholinked nucleotides, and exposed at the bottom to excitation illumination. The nucleotides held by the polymerase prior to incorporation emit an extended signal that identifies the base being incorporated, and so the ZMWs provide the windows to observe DNA sequencing in real-time.

Optimizing clinical diagnostics is important for the widespread adoption of next-generation sequencing. Organizations such as the Genome in a Bottle Consortium are focused on providing resources to clinical laboratory clients to reduce ambiguity in sequence analysis.

“A clinical laboratory will often need to establish the accuracy of their sequencing and analysis methods,” says Justin Zook, Ph.D., a founding member of the Genome in a Bottle Consortium and a researcher at the National Institute of Standards and Technology (NIST).
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DNA ‘vaccine’ that sterilizes mice, could lead to one-shot birth control

DNA ‘vaccine’ that sterilizes mice, could lead to one-shot birth control | Amazing Science |

Animal birth control could soon be just a shot away: A new injection makes male and female mice infertile by tricking their muscles into producing hormone-blocking antibodies. If the approach works in dogs and cats, researchers say, it could be used to neuter and spay pets and to control reproduction in feral animal populations. A similar approach could one day spur the development of long-term birth control options for humans.

“This looks incredibly promising,” says William Swanson, director of animal research at the Cincinnati Zoo and Botanical Garden in Ohio. “We’re all very excited about this approach; that it’s going to be the one that really works.”

For decades, the go-to methods for controlling animal reproduction have been spay or neuter surgeries. But the surgeries, which require animals to be anesthetized, can be expensive—one reason so many dogs and cats remain unfixed and feral animal populations continue to grow. Nearly 2.7 million dogs and cats were euthanized in U.S. shelters last year. A cheaper, faster method of sterilization is considered a holy grail for animal population control. 

To get there, researchers have already created vaccines that trigger an immune response in animals. This response produces antibodies that block gonadotropin-releasing hormone (GnRH), required by all mammals to turn on the pathways that spur egg or sperm development. The vaccines in this class—including deer contraceptive GonaCon—have been shown to effectively work as both male and female birth control in animals. But, like many human immunizations, the vaccines rely on an immune response that eventually dwindles away, forcing the use of booster shots every few years.

Biologist Bruce Hay of the California Institute of Technology in Pasadena and colleagues took a different approach to blocking GnRH. Rather than rely on animals’ immune systems to create antibodies, he and his colleagues engineered a piece of DNA that—when packaged inside inactive virus shells and injected into mice—turned their muscle cells into anti-GnRH antibody factories. Because muscle cells are some of the longest lasting in the body, they continue to churn out the antibodies for 10 or more years. Both male and female mice with high enough levels of the antibodies were rendered completely infertile when Hay’s team allowed them to mate 2 months later, the team reports online today in Current Biology.

Via Integrated DNA Technologies
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Gene-editing record smashed in pigs: 60 genes edited

Gene-editing record smashed in pigs: 60 genes edited | Amazing Science |

Researchers modify more than 60 genes in effort to enable organ transplants into humans.

For decades, scientists and doctors have dreamed of creating a steady supply of human organs for transplantation by growing them in pigs. But concerns about rejection by the human immune system and infection by viruses embedded in the pig genome have stymied research. Now, bymodifying more than 60 genes in pig embryos — ten times more than have been edited in any other animal — researchers believe they may have produced a suitable non-human organ donor.

The work was presented on 5 October 2015 at a meeting of the US National Academy of Sciences (NAS) in Washington DC on human gene editing. Geneticist George Church of Harvard Medical School in Boston, Massachusetts, announced that he and colleagues had used the CRISPR/Cas9 gene-editing technology to inactivate 62 porcine endogenous retroviruses (PERVs) in pig embryos. These viruses are embedded in all pigs’ genomes and cannot be treated or neutralized.It is feared that they could cause disease in human transplant recipients.

Church’s group also modified more than 20 genes in a separate set of pig embryos, including genes that encode proteins that sit on the surface of pig cells and are known to trigger a human immune response or cause blood clotting. Church declined to reveal the exact genes, however, because the work is as yet unpublished.Eventually, pigs intended for organ transplants would need both these modifications and the PERV deletions.

Via Integrated DNA Technologies
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BGI is planning to sell their gene-edited 'micropigs' as pets

BGI is planning to sell their gene-edited 'micropigs' as pets | Amazing Science |

Cutting-edge gene-editing techniques have produced an unexpected byproduct — tiny pigs that a leading Chinese genomics institute will soon sell as pets.

BGI in Shenzhen, the genomics institute that is famous for a series of high-profile breakthroughs in genomic sequencing, originally created the micropigs as models for human disease, by applying a gene-editing technique to a small breed of pig known as Bama. On 23 September 2015, at the Shenzhen International Biotech Leaders Summit in China, BGI revealed that it would start selling the pigs as pets. The animals weigh about 15 kilograms when mature, or about the same as a medium-sized dog.

At the summit, the institute quoted a price tag of 10,000 yuan (US$1,600) for the micropigs, but that was just to "help us better evaluate the market”, says Yong Li, technical director of BGI’s animal-science platform. In future, customers will be offered pigs with different coat colors and patterns, which BGI says it can also set through gene editing.

With gene editing taking biology by storm, the field's pioneers say that the application to pets was no big surprise. Some also caution against it. “It's questionable whether we should impact the life, health and well-being of other animal species on this planet light-heartedly,” says geneticist Jens Boch at the Martin Luther University of Halle-Wittenberg in Germany. Boch helped to develop the gene-editing technique used to create the pigs, which uses enzymes known as TALENs (transcription activator-like effector nucleases) to disable certain genes.

How to regulate the various applications of gene-editing is an open question that scientists are already discussing with agencies across the world. BGI agrees on the need to regulate gene editing in pets as well as in the medical research applications that make up the core of its micropig activities. Any profits from the sale of pets will be invested in this research. “We plan to take orders from customers now and see what the scale of the demand is,” says Li.

The decision to sell the pigs as pets surprised Lars Bolund, a medical geneticist at Aarhus University in Denmark who helped BGI to develop its pig gene-editing programme, but he admits that they stole the show at the Shenzhen summit. “We had a bigger crowd than anyone,” he says. “People were attached to them. Everyone wanted to hold them.”

They could meet a preexisting demand. In the United States, for instance, reports have surfaced of people who wanted a porcine lap pet, but were disappointed when animals touted as 'teacup' pigs weighing only 5 kilograms grew into 50-kilogram animals. Genetically-edited micropigs stay reliably small, the BGI team says.

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A plasmonic nanorod that walks on DNA origami

A plasmonic nanorod that walks on DNA origami | Amazing Science |

Researchers from the Max Planck Institute for Intelligent Systems in Stuttgart have developed a gold nanocylinder equipped with discrete DNA strands as ‘feet’ that can walk across a DNA origami platform. They are able to trace the movements of the nanowalker, which is smaller than the optical resolution limit, by exciting plasmons in the gold nanocylinder. Plasmons are collective oscillations of numerous electrons. The excitation changes the ray of light, thus allowing the researchers to actually observe the nanowalker. Their main objective is to use such mobile plasmonic nanoobjects to study how miniscule particles interact with light.

Nanomachines – i.e. mechanical devices with dimensions of nanometers – could one day carry out specific tasks in fields such as medicine, information processing, chemistry or scientific research, according to nanotechnology experts.

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The Genesis Engine: Can we eliminate disease and solve world hunger?

The Genesis Engine: Can we eliminate disease and solve world hunger? | Amazing Science |

SPINY GRASS AND SCRAGGLY PINES creep amid the arts-and-crafts buildings of the Asilomar Conference Grounds, 100 acres of dune where California's Monterey Peninsula hammerheads into the Pacific. It's a rugged landscape, designed to inspire people to contemplate their evolving place on Earth. So it was natural that 140 scientists gathered here in 1975 for an unprecedented conference.

They were worried about what people called “recombinant DNA,” the manipulation of the source code of life. It had been just 22 years since James Watson, Francis Crick, and Rosalind Franklin described what DNA was—deoxyribonucleic acid, four different structures called bases stuck to a backbone of sugar and phosphate, in sequences thousands of bases long. DNA is what genes are made of, and genes are the basis of heredity.

Preeminent genetic researchers like David Baltimore, then at MIT, went to Asilomar to grapple with the implications of being able to decrypt and reorder genes. It was a God-like power—to plug genes from one living thing into another. Used wisely, it had the potential to save millions of lives. But the scientists also knew their creations might slip out of their control. They wanted to consider what ought to be off-limits.

By 1975, other fields of science—like physics—were subject to broad restrictions. Hardly anyone was allowed to work on atomic bombs, say. But biology was different. Biologists still let the winding road of research guide their steps. On occasion, regulatory bodies had acted retrospectively—after Nuremberg, Tuskegee, and the human radiation experiments, external enforcement entities had told biologists they weren't allowed to do that bad thing again. Asilomar, though, was about establishing prospective guidelines, a remarkably open and forward-thinking move.

Fast forward to 2015. Baltimore joined 17 other researchers for another California conference, this one at the Carneros Inn in Napa Valley. “It was a feeling of déjà vu,” Baltimore says. There he was again, gathered with some of the smartest scientists on earth to talk about the implications of genome engineering. The stakes, however, have changed. Everyone at the Napa meeting had access to a gene-editing technique called Crispr-Cas9. The first term is an acronym for “clustered regularly interspaced short palindromic repeats,” a description of the genetic basis of the method; Cas9 is the name of a protein that makes it work. Technical details aside, Crispr-Cas9 makes it easy, cheap, and fast to move genes around—any genes, in any living thing, from bacteria to people. “These are monumental moments in the history of biomedical research,” Baltimore says. “They don't happen every day.”

Using the three-year-old technique, researchers have already reversed mutations that cause blindness, stopped cancer cells from multiplying, and made cells impervious to the virus that causes AIDS. Agronomists have rendered wheat invulnerable to killer fungi like powdery mildew, hinting at engineered staple crops that can feed a population of 9 billion on an ever-warmer planet. Bioengineers have used Crispr to alter the DNA of yeast so that it consumes plant matter and excretes ethanol, promising an end to reliance on petrochemicals. Startups devoted to Crispr have launched.

International pharmaceutical and agricultural companies have spun up Crispr R&D. Two of the most powerful universities in the US are engaged in a vicious war over the basic patent. Depending on what kind of person you are, Crispr makes you see a gleaming world of the future, a Nobel medallion, or dollar signs.

The technique is revolutionary, and like all revolutions, it's perilous. Crispr goes well beyond anything the Asilomar conference discussed. It could at last allow genetics researchers to conjure everything anyone has ever worried they would—designer babies, invasive mutants, species-specific bioweapons, and a dozen other apocalyptic sci-fi tropes. It brings with it all-new rules for the practice of research in the life sciences. But no one knows what the rules are—or who will be the first to break them.

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