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  • richardmitnick 11:10 am on November 12, 2015 Permalink | Reply
    Tags: , , , Genetics   

    From AAAS: “The 3230 genes you can’t do without” 



    11 November 2015
    Elizabeth Pennisi

    By comparing sets of genes from tens of thousands of people, researchers have found some that the body can’t seem to live without. Jane Ades/NHGRI

    Fiddle just a little bit with any one of about 3200 genes in the human body and you could be toast. That’s the conclusion of a new study, which finds that about 15% of our 20,000 genes are so critical to our livelihood that even minor mutations can kill us before we’re born. The findings should help researchers better track down the genes that cause human disease.

    Given how useful any insights into gene function are for understanding the genetic basis of disease, the data are “priceless,” says Kári Stephánsson, a geneticist at deCODE in Reykjavík.

    The new study, which was recently posted to a preprint repository but has not yet been published in a peer-reviewed publication, was the result of researchers comparing the parts of the genome known as exomes, which code for proteins, from 60,000 people—10 times more than had ever been attempted. Researchers led by Daniel MacArthur, a geneticist at the Broad Institute of the Massachussetts Institute of Technology and Harvard University in Cambridge, Massachusetts, achieved this feat by reaching out to teams around the world who had collected their own sets of exomes. Among all those genes, the researchers found 10 million variants—places within genes that varied from person to person.

    MacArthur’s team calculated how many variants each gene should have if those changes arise by chance. Then they compared that to the number of variants actually found for each gene. The result: 3230 genes that had either no observed variation, or compared to what was expected, much, much less of the kind of changes that could lead to a malfunction of the gene.

    Such data suggests that, whenever one of these genes mutates, the embryo usually dies or the person is too sick to reproduce—so the variation disappears. ”Genes that displayed no variants should be essential or play crucial biological functions,” says Ping Xu, a molecular microbiologist at Virginia Commonwealth University in Richmond.

    Ping and others have similarly found such essential genes in bacteria or in mice. And many of the highlighted human genes are associated with the same critical cellular operations, such as the cell’s protein-building factories, as in those species, MacArthur’s group reports. About 20% of the human genes uncovered by the analysis are already associated with diseases, but many are not—yet. They are the first places David Goldstein, a geneticist at Columbia University in New York City who was not involved with the work, says he will look for connections to medical conditions. And because they seem vital “these genes can be specifically monitored during drug development for potential side effects and cytotoxicity,” Xu says.

    The key to the success of MacArthur’s team, say other researchers, was gathering so much DNA data. (MacArthur declined to comment since the paper isn’t officially published yet.) “They do a really nice job of showing that you get a lot more information by studying an order of magnitude more people,” says Joshua Akey, a population geneticist at the University of Washington in Seattle.

    Even so, Goldstein is quick to point out that 3230 is not the complete set of essential genes in the human body and that only by studying more exomes will researchers be able to refine that number. Furthermore, exomes don’t cover DNA in between genes, which help regulate gene activity, and variation there can also be important. Finally, what researchers really want to know is what specific part of each gene is essential. Bottom line, Goldstein says: “This is another step on a very long road that we are on to understand what does and doesn’t happen in the human genome.”

    See the full article here .

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  • richardmitnick 7:59 am on October 26, 2015 Permalink | Reply
    Tags: , Genetics,   

    From U Washington: “New UW model helps zero in on harmful genetic mutations” 

    U Washington

    University of Washington

    October 22, 2015
    Jennifer Langston

    A new UW model can help narrow down which genetic mutations affect how genes splice and contribute to disease. In this illustration, the cell’s splicing machinery is trying to pick which “cutting” sites (pictured as white flags) it should use. Jennifer Sunami

    Between any two people, there are likely to be at least 10 million differences in the genetic sequence that makes up their DNA.

    Most of these differences don’t alter the way cells behave or cause health problems. But some genetic variations greatly increase the likelihood that a person will develop cancer, diabetes, colorblindness or a host of other diseases.

    Despite rapid advances in our ability to map an individual’s genome — the precise coding that makes up his or her genes — we know much less about which mutations or anomalies actually cause disease.

    Now, a new model and publicly available Web tool developed by University of Washington researchers can more accurately and quantitatively predict which genetic mutations significantly change how genes splice and may warrant increased attention from disease researchers and drug developers.

    The model — the first to train a machine learning algorithm on vast amounts of genetic data created with synthetic biology techniques — is outlined in a paper published in the Oct. 22 issue of Cell.

    “Some people have variations in a particular gene, but what you really want to know is whether those matter or not,” said lead author Alexander Rosenberg, a UW electrical engineering doctoral student. “This model can help you narrow down the universe — hugely — of the mutations that might be most likely to cause disease.”

    In particular, the model predicts how these genetic sequence variations affect alternative splicing — a critical process that enables a single gene to create many different forms of proteins by including or excluding snippets of RNA.

    “This is an avenue that’s unexplored to a large extent,” said Rosenberg. “It’s fairly easy to look at how mutations affect proteins directly, but people have not been able to look at how mutations affect proteins through splicing.”

    For example, a scientist studying the genetic underpinnings of lung cancer or depression or a particular birth defect could type the most commonly shared DNA sequence in a particular gene into the Web tool, as well as multiple variations. The model will tell the scientist which mutations cause outsized differences in how the gene splices — which could be a sign of trouble — and which have little or no effect.

    The researcher would still need to investigate whether a particular genetic sequence causes harmful changes, but the online tool can help rule out the many variations that aren’t likely to be of interest to health researchers. To validate the model’s predictive powers, the UW team tested it on a handful of well-understood mutations such as those in the BRCA2 gene that have been linked to breast and ovarian cancer.

    Compared to previously published models, the UW approach is roughly three times more accurate at predicting the extent to which a mutation will cause genetic material to be included or excluded in the protein-making process — which can change how those proteins function and cause biological processes to go awry.

    The UW team used synthetic biology and DNA sequencing techniques to create a massive library of genetic data. By training a machine learning algorithm on that large synthetic dataset, the UW model can make accurate predictions about the human genome.University of Washington

    That’s because the UW team used a new approach that combines synthetic biology and machine learning techniques to create the model.

    Machine learning algorithms — which enable computers to infer rules and “learn” from vast amounts of data — become more accurate the more data they’re exposed to. But the human genome only has roughly 25,000 genes that create proteins.

    Using common molecular biology techniques, the UW team created a library of over 2 million synthetic “mini-genes” by including random DNA sequences. Then they determined how each random sequence element affected where genes spliced and what types of RNA were produced — which ultimately determines which proteins get made.

    That larger library of synthetic data essentially teaches the model to become smarter, said lead author Georg Seelig, a UW assistant professor of electrical engineering and of computer science & engineering.

    “Our algorithm works super well because it was trained on these synthetic datasets. And the reason it works so well is because that synthetic dataset is orders of magnitude larger than the training set you get from the actual human genome,” said Seelig.

    “It is remarkable that a model trained entirely on synthetic data can outperform models trained directly on the human genome on the task of predicting the impact of mutations in people,” he said.

    Next research steps include expanding the approach beyond alternative splicing to other processes that determine how genes are expressed.

    In the meantime, by making the Web tool free and publicly available, the team hopes other scientists will use their alternative splicing model — and ultimately make progress in narrowing down which natural genetic variations are most meaningful when it comes to health and disease.

    “Other research groups and companies can use our model to rank the areas of interest to them,” Seelig said. “We hope other people will take this further to more clinical applications.”

    Co-authors include former UW doctoral student Rupali P. Patwardhan and associate professor Jay Shendure in the UW Department of Genome Sciences.

    For more information, contact Seelig at gseelig@uw.edu.

    See the full article here .

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  • richardmitnick 3:24 am on October 16, 2015 Permalink | Reply
    Tags: , , , Genetics   

    From EPFL: “The future of farming depends on local breeds” 

    EPFL bloc

    Ecole Polytechnique Federale Lausanne

    Jan Overney

    The dwindling genetic diversity of farm animals is increasingly becoming a threat to livestock production. Although new DNA technologies can help us address this problem, changing habits to preserve local lineages may prove to be challenging. No image credit.

    It is hard to overestimate the importance of global livestock production to society and the economy. It constitutes the main source of income for 1.3 billion farmers, providing vital food for 800 million subsistence farmers, and making up 40% of global agricultural GDP. But overbreeding and dwindling genetic diversity could limit the ability of livestock populations to adapt the environmental changes, such as global warming and related new diseases. Currently on the sidelines, lesser-known livestock breeds and the DNA they carry could become key to securing the future of livestock farming.

    For four years leading up to 2014, a European research project chaired by EPFL took stock of the past, present, and future of farm animal genetic resources and outlined the questions of highest priority for research, infrastructure and policy development for the coming decade. A selection of the project’s scientific output has now been published by the open access journal Frontiers in Genetics and is available online in the form of 31 research papers.

    A shrinking genetic reservoir

    Over the past 100 years, many local breeds have gone extinct, as more productive industrial breeds have taken over. Even within these breeds, the genetic diversity between individuals is shrinking. So why does this matter? “A reduction of genetic diversity goes hand with hand with a reduction of the species’ capacity to adapt to new diseases, warmer temperatures, or new food sources,” says Stéphane Joost, the project’s chair.

    “Studying 1,200 sheep from 32 old, native breeds from around the world, we previously identified a specific gene involved in regulating their metabolism, whose presence correlated strongly with the amount of incident solar radiation – a genetic trait that made them better adapted to their environment than cosmopolitan breeds that are more productive in the short term,” says Joost. If breeds carrying such specific adaptations disappear, so too will the coping strategies they acquired throughout evolution.

    The better choice?

    Joost’s advice to farmers: “Farmers should keep their local, well adapted breeds,” he urges. They may be less productive than their industrially bred cousins, but in developing countries with extreme climates sticking to them is often the wiser choice – a lesson that many farmers learn the hard way. After investing their savings to crossbreed a species of cow local to West Africa with an industrial breed, farmers in Burkina Faso first reaped the fruits of their investment, until they realized that all of the mixed breed’s offspring were poorly adapted to their climate and eventually died. “Only local breeds are adapted to resist to such harsh environments and withstand diseases such as trypanosomiasis, spread by the tsetse fly,” says Joost.

    An archive of adaptation

    Understanding the genetic history of today’s breeds could help us find ways of adapting in the future, says Joost. “What ancestral animals conferred the species with a specific trait? And what can we do today to recover that same trait?” he asks. Knowing, for example, exactly which native species were crossbred to produce today’s breeds could help pinpoint certain well-adapted genes present in the native species that may have been lost. In the same way, well-adapted local breeds that were abandoned to the point of extinction could be recreated by cross-breeding the ancestral species they emerged from.

    To ensure that the research carried out in this project finds its way into the agricultural community, the 31 studies will be compiled into an e-book, which will also be made available in print and distributed to stakeholders in developing countries by the FAO. But changing habits will be an uphill battle, as it involves sacrificing short-term profits for long-term sustainability – a problem that Joost and the co-organizers of the research project are well aware of. “Throughout this project, we emphasized the need to work with social scientists to effectively influence the habits of the breeders associations and other stakeholders. This is one front on which we still have much to do,” he concludes.

    See the full article here .

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    EPFL is Europe’s most cosmopolitan technical university. It receives students, professors and staff from over 120 nationalities. With both a Swiss and international calling, it is therefore guided by a constant wish to open up; its missions of teaching, research and partnership impact various circles: universities and engineering schools, developing and emerging countries, secondary schools and gymnasiums, industry and economy, political circles and the general public.

  • richardmitnick 6:58 am on October 10, 2015 Permalink | Reply
    Tags: , Genetics,   

    From Nature: “Gene-editing record smashed in pigs” 

    Nature Mag

    06 October 2015
    Sara Reardon

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

    Geneticist George Church has co-founded a company that is developing genetically modified pigs to grow organs for human transplant. Jessica Rinaldi/Reuters

    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, by modifying 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 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.

    The gene-edited pigs will be raised in isolation from pathogens. ableimages / Alamy Stock Photo

    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.

    Preparing for implantation

    “This is something I’ve been wanting to do for almost a decade,” Church says. A biotech company that he co-founded to produce pigs for organ transplantation, eGenesis in Boston, is now trying to make the process as cheap as possible.

    Church released few details about how his team managed to remove so many pig genes. But he says that both sets of edited pig embryos are almost ready to implant into mother pigs. eGenesis has procured a facility at Harvard Medical School where the pigs will be implanted and raised in isolation from pathogens.

    Jennifer Doudna, a biochemist at University of California, Berkeley, who was one of the inventors of CRISPR/Cas9 technology, is impressed by the number of edited genes. If the work holds up, she says, it could be useful for synthetic-biology applications where genes can be switched on and off. In microorganisms, creating these circuits requires the insertion or modification of multiple genes that regulate one another.

    Cutting multiple genes will also be useful for human therapies, says George Daley, a stem-cell biologist at Harvard Medical School, because many diseases with a genetic component involve more than one gene.

    Nature doi:10.1038/nature.2015.18525

    See the full article here .

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  • richardmitnick 2:33 pm on September 25, 2015 Permalink | Reply
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    From MIT: “New system for human genome editing has potential to increase power and precision of DNA engineering” 

    MIT News

    September 25, 2015
    Broad Institute

    CRISPR systems are found in many different bacterial species, and have evolved to protect host cells against infection by viruses. Image courtesy of Broad Institute/Science Photo Images

    CRISPR-Cpf1 offers simpler approach to editing DNA; technology could disrupt scientific and commercial landscape.

    A team including the scientist who first harnessed the CRISPR-Cas9 system for mammalian genome editing has now identified a different CRISPR system with the potential for even simpler and more precise genome engineering.

    In a study published today in Cell, Feng Zhang and his colleagues at the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT, with co-authors Eugene Koonin at the National Institutes of Health, Aviv Regev of the Broad Institute and the MIT Department of Biology, and John van der Oost at Wageningen University, describe the unexpected biological features of this new system and demonstrate that it can be engineered to edit the genomes of human cells.

    “This has dramatic potential to advance genetic engineering,” says Eric Lander, director of the Broad Institute. “The paper not only reveals the function of a previously uncharacterized CRISPR system, but also shows that Cpf1 can be harnessed for human genome editing and has remarkable and powerful features. The Cpf1 system represents a new generation of genome editing technology.”

    CRISPR sequences were first described in 1987, and their natural biological function was initially described in 2010 and 2011. The application of the CRISPR-Cas9 system for mammalian genome editing was first reported in 2013, by Zhang and separately by George Church at Harvard University.

    In the new study, Zhang and his collaborators searched through hundreds of CRISPR systems in different types of bacteria, searching for enzymes with useful properties that could be engineered for use in human cells. Two promising candidates were the Cpf1 enzymes from bacterial species Acidaminococcus and Lachnospiraceae, which Zhang and his colleagues then showed can target genomic loci in human cells.

    “We were thrilled to discover completely different CRISPR enzymes that can be harnessed for advancing research and human health,” says Zhang, the W.M. Keck Assistant Professor in Biomedical Engineering in MIT’s Department of Brain and Cognitive Sciences.

    The newly described Cpf1 system differs in several important ways from the previously described Cas9, with significant implications for research and therapeutics, as well as for business and intellectual property:

    First: In its natural form, the DNA-cutting enzyme Cas9 forms a complex with two small RNAs, both of which are required for the cutting activity. The Cpf1 system is simpler in that it requires only a single RNA. The Cpf1 enzyme is also smaller than the standard SpCas9, making it easier to deliver into cells and tissues.

    Second, and perhaps most significantly: Cpf1 cuts DNA in a different manner than Cas9. When the Cas9 complex cuts DNA, it cuts both strands at the same place, leaving “blunt ends” that often undergo mutations as they are rejoined. With the Cpf1 complex the cuts in the two strands are offset, leaving short overhangs on the exposed ends. This is expected to help with precise insertion, allowing researchers to integrate a piece of DNA more efficiently and accurately.

    Third: Cpf1 cuts far away from the recognition site, meaning that even if the targeted gene becomes mutated at the cut site, it can likely still be recut, allowing multiple opportunities for correct editing to occur.

    Fourth: The Cpf1 system provides new flexibility in choosing target sites. Like Cas9, the Cpf1 complex must first attach to a short sequence known as a PAM, and targets must be chosen that are adjacent to naturally occurring PAM sequences. The Cpf1 complex recognizes very different PAM sequences from those of Cas9. This could be an advantage in targeting some genomes, such as in the malaria parasite as well as in humans.

    “The unexpected properties of Cpf1 and more precise editing open the door to all sorts of applications, including in cancer research,” says Levi Garraway, an institute member of the Broad Institute, and the inaugural director of the Joint Center for Cancer Precision Medicine at the Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and the Broad Institute. Garraway was not involved in the research.

    An open approach to empower research

    Zhang, along with the Broad Institute and MIT, plan to share the Cpf1 system widely. As with earlier Cas9 tools, these groups will make this technology freely available for academic research via the Zhang lab’s page on the plasmid-sharing website Addgene, through which the Zhang lab has already shared Cas9 reagents more than 23,000 times with researchers worldwide to accelerate research. The Zhang lab also offers free online tools and resources for researchers through its website.

    The Broad Institute and MIT plan to offer nonexclusive licenses to enable commercial tool and service providers to add this enzyme to their CRISPR pipeline and services, further ensuring availability of this new enzyme to empower research. These groups plan to offer licenses that best support rapid and safe development for appropriate and important therapeutic uses.

    “We are committed to making the CRISPR-Cpf1 technology widely accessible,” Zhang says. “Our goal is to develop tools that can accelerate research and eventually lead to new therapeutic applications. We see much more to come, even beyond Cpf1 and Cas9, with other enzymes that may be repurposed for further genome editing advances.”

    See the full article here .

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  • richardmitnick 12:13 pm on September 18, 2015 Permalink | Reply
    Tags: , Gene splicing, Genetics,   

    From New Scientist: “Gene editing: Bring it on” 


    New Scientist

    18 September 2015
    Jessica Griggs

    “Einstein said our technology exceeds our humanity. I don’t buy that” (Image: Jason Grow Photography)

    Breakthroughs in DNA technology are opening the door to a superhuman future. Genetic engineering pioneer George Church says we have nothing to fear.

    There has been a lot of excitement lately over the new gene-editing technology, CRISPR. How does it work?

    Gene editing is snipping out a targeted DNA sequence and replacing it with another. It used to be time-consuming and imprecise, but now you can edit any living genome, using your computer to target a stretch of DNA. Guides made of bespoke RNA lead the CRISPR molecular machinery to the target, where an enzyme makes a cut. This either destroys the function of the DNA in that location or allows you to change its functioning by manipulating how the cells repair the cut, for example by inserting a genetic sequence of your choice.

    What will we be able to do with CRISPR?

    It could enable gene therapies that would allow physicians to fix genetic diseases, including some types of blindness, the blood disorder beta thalassemia and the neurodegenerative disorder Tay-Sachs disease. It could also mean new approaches to treating cancers and viral infections, including HIV.

    Other techniques could allow helpful DNA to spread through wild animal populations – which may allow us to eliminate infectious diseases like malaria.

    Earlier this year, there was controversy when a team in China attempted to use CRISPR to edit the genes of non-viable human embryos. For some people this still crossed an ethical line. What are your thoughts?

    In the early days of any field, if you mess up enough, you don’t just mess up your lab, you mess up all the labs. I don’t think this brouhaha will kill gene editing – they didn’t hurt any patients. But they were incautious.

    From a technical point of view, there are several widely known techniques that have been proven to improve the specificity and efficacy of CRISPR gene editing, some of which were developed in my lab. The Chinese group must have known that their work was going to get a lot of attention, so it was disappointing that they chose not to use these techniques. They may have felt that if they waited to do it the right way, another lab would have scooped them. In practice these other labs, mine included, are not doing CRISPR research with human embryos, so I don’t know what they were worried about.

    Mediocre science is not the same as evil science – after all, the experiments they did are legal in most countries.

    So you’re not worried about the ethical issues that have been raised?

    For me, the safety issues are the ethical issues, and the safety issues are not fundamentally different from those of any new therapeutic. Gene-editing techniques are being tested in animals extensively, in primates as well as rodents, and will eventually move into people.

    I’m a professional worrier. But the form that my worry takes is action. As soon as somebody expresses something to me that they think is wrong with the world or with research, I say “let’s work on this”. We can innovate on safety measures.

    Some people are against any tinkering with the gene pool – summoning the ever-present spectre of designer babies.

    We humans already tinker with the gene pool with inherited diseases such as Tay-Sachs: genetic counselling before or after conception can help parents to decide on the health of their future children.

    We tinker with the gene pool every time we fly at high altitude, which increases random mutations in developing sperm and egg cells. These things are allowed. If you don’t like the concept of tinkering with the gene pool, then ban it across the board. Don’t be exceptional about CRISPR.

    “People worry that gene editing is irreversible, but that notion is a straw man”

    Then there’s the issue of what we value. Do we value long life, intelligence, athleticism, beauty? We are already making our children more educated than their ancestors, and typically we do that without the permission of the children. People pay for products that improve beauty and athleticism. If you don’t think those are good values, then ban tinkering with them. But be fair. Don’t ban a particular form of it – unless it’s unsafe.

    Enzymes (pale blue) cuts target DNA (red), guided by RNA (yellow) – it’s CRISPR in action (Image: Bang Wong, from source material provided by Feng Zhang)

    Should unborn children have the right not to have their parents genetically dictate who they become, or is it the parents’ choice?

    Parents owe it to their children to provide them with a good start. Education, chores, nutrition, dress code, faith and curfews are often dictated by parents for the good of the child. And parents already use genetic counselling to guide pre-conception and prenatal choices, to dictate that the child will not be burdened by serious genetic disease. Once those children grow up, they can choose different dictates for their own children as new information about genetics and child rearing becomes available.

    There are also concerns that genetic modification affecting sperm and eggs will produce changes that are irreversible and that can be passed down through the generations.

    The irreversibility argument strikes me as a straw man because, clearly, gene editing is not irreversible on a population-wide level.

    If the population is changing because individuals are making decisions, it can change back if governments or individuals make alternative decisions. In fact, it can change back more readily because the technology is improving all the time and the costs are reducing. Now, it could be that people won’t want to reverse the changes, but that’s telling you that the change is valuable in some way.

    If humanity doesn’t take the opportunity to advance genetic engineering in people, are we doing ourselves a disservice?

    Absolutely. This question should come up more frequently. With seven billion people and growing, sitting still is not really a great option. For example, we could wipe out malaria using a gene drive – a technique that would allow a malaria-resistance gene to spread through a population of mosquitoes extremely rapidly.

    That could be risky.

    Some of us may say that gene drives are too risky in general because of unknown unknowns – like perhaps causing the extinction of a mosquito species. But if you did, it’s unlikely that that is going to kill any other animal. And every year that we hesitate, 600,000 people die of malaria unnecessarily and another couple of million get sick and miss days at work. That’s a pretty big price to pay.

    You’re also interested in what’s called genetic augmentation. Isn’t using gene therapy in that way, whether for physical or mental enhancement, controversial too?

    It’s less controversial because it would be in consenting adults. If a majority agrees that adults can be augmented – using a new drug, device, or gene therapy – then as long as it passes the usual safety and efficacy rules of the US Food and Drug Administration (FDA), in my view it’s not controversial enough to prevent rapid adoption.

    You’ve famously come up with a list of 10 particularly protective but rare gene variants that we might all benefit from.

    Yes. For example, PCSK9 protects you from cardiovascular disease, and it’s “superhuman” in the sense that people who have it are well beyond the average human in terms of low cardiovascular risk. Three others on the list – MSTN, LRP, APOE – will probably lead to therapies to prevent muscle degeneration, osteoporosis and dementia.

    What about genes unrelated to disease? If we go in for editing such genes, what kind of society will we end up with?

    It comes down to what societies value, and then what individuals want.

    I don’t think everyone will want the same thing: we won’t all suddenly become exactly 5 feet 10 inches tall, with blonde hair and blue eyes. I think augmentation will actually increase diversity.

    Some of it will be driven by need or ambition. People who want to go to space may want super-strong bones to protect them from osteoporosis in low gravity, while people who go to live at the bottom of the ocean will want a different set of modifications. And people who want to be super bankers are probably going to want a different set than the people who want to be super athletes. There isn’t a best kind of human, just like there isn’t a best kind of car.

    If you’re going to worry – which I do all the time – I would worry about adult augmentation, because it will spread fast. If I were to augment a child, an embryo, it will take 20 years before they have any significant impact on society.

    But if I come up with an augmentation that improves adult intelligence, news of that will go through the internet at light speed and a lot of people will try it. And then if it’s successful in the first million people who try it, then there could be a billion people who try it.

    In 2012 you published a book entitled Regenesis, and you have talked about your lab as a centre for new technology aiming to rebuild creation to suit humans. Set that alongside your appearance and your name, and is it any wonder people accuse you of playing God?

    It’s certainly not my intention. But we’re engineers – making our world suit us is what we do. It’s what humans do. The term “playing God” is mainly used to imply that you are doing something beyond your means.

    I agree that we need to be cautious and I actually feel that humanity generally does move forward in steps. It can seem very fast and can, ultimately, happen in gigantic leaps – like landing on the moon and eliminating smallpox – but these things are done cautiously.

    Yet technology is advancing at a blistering pace.

    Einstein said our technology exceeds our humanity. I don’t buy that. I think that even when technology is going very fast, we have tried-and-tested traditional ways of reining it in. We don’t need special bans or a moratorium – we have the Environmental Protection Agency, we have the FDA. We need to think big, but also think carefully.

    See the full article here .

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  • richardmitnick 2:12 pm on September 7, 2015 Permalink | Reply
    Tags: , , Genetics,   

    From phys.org: “Scientists create world’s largest protein map to reveal which proteins work together in a cell” 


    September 7, 2015
    No Writer Credit

    Scientists have uncovered tens of thousands of new protein interactions, accounting for about a quarter of all estimated protein contacts in a cell. Credit: Jovana Drinkjakovic

    A multinational team of scientists have sifted through cells of vastly different organisms, from amoebae to worms to mice to humans, to reveal how proteins fit together to build different cells and bodies.

    This tour de force of protein science, a result of a collaboration between seven research groups from three countries, led by Professor Andrew Emili from the University of Toronto’s Donnelly Centre and Professor Edward Marcotte from the University of Texas at Austin, uncovered tens of thousands of new protein interactions, accounting for about a quarter of all estimated protein contacts in a cell.

    When even a single one of these interactions is lost it can lead to disease, and the map is already helping scientists spot individual proteins that could be at the root of complex human disorders. The data will be available to researchers across the world through open access databases.

    The study comes out in Nature on September 7.

    While the sequencing of the human genome more than a decade ago was undoubtedly one of the greatest discoveries in biology, it was only the beginning of our in-depth understanding of how cells work. Genes are just blueprints and it is the genes’ products, the proteins, that do much of the work in a cell.

    Proteins work in teams by sticking to each other to carry out their jobs. Many proteins come together to form so called molecular machines that play key roles, such a building new proteins or recycling those no longer needed by literally grinding them into reusable parts. But for the vast majority of proteins, and there are tens of thousands of them in human cells, we still don’t know what they do.

    This is where Emili and Marcotte’s map comes in. Using a state-of-the-art method developed by the groups, the researchers were able to fish thousands of protein machineries out of cells and count individual proteins they are made of. They then built a network that, similar to social networks, offers clues into protein function based on which other proteins they hang out with. For example, a new and unstudied protein, whose role we don’t yet know, is likely to be involved in fixing damage in a cell if it sticks to cell’s known “handymen” proteins.

    Today’s landmark study gathered information on protein machineries from nine species that represent the tree of life: baker’s yeast, amoeba, sea anemones, flies, worms, sea urchins, frogs, mice and humans. The new map expands the number of known protein associations over 10 fold, and gives insights into how they evolved over time.

    “For me the highlight of the study is its sheer scale. We have tripled the number of protein interactions for every species. So across all the animals, we can now predict, with high confidence, more than 1 million protein interactions – a fundamentally ‘big step’ moving the goal posts forward in terms of protein interactions networks,” says Emili, who is also Ontario Research Chair in Biomarkers in Disease Management and a professor in the Department of Molecular Genetics.

    The researchers discovered that tens of thousands of protein associations remained unchanged since the first ancestral cell appeared, one billion years ago (!), preceding all of animal life on Earth.

    “Protein assemblies in humans were often identical to those in other species. This not only reinforces what we already know about our common evolutionary ancestry, it also has practical implications, providing the ability to study the genetic basis for a wide variety of diseases and how they present in different species,” says Marcotte.

    The map is already proving useful in pinpointing possible causes of human disease. One example is a newly discovered molecular machine, dubbed Commander, which consists of about a dozen individual proteins. Genes that encode some of Commander’s components had previously been found to be mutated in people with intellectual disabilities but it was not clear how these proteins worked.

    Because Commander is present in all animal cells, graduate student Fan Tu went on to disrupt its components in tadpoles, revealing abnormalities in the way brain cells are positioned during embryo development and providing a possible origin for a complex human condition.

    “With tens of thousands of other new protein interactions, our map promises to open many more lines of research into links between proteins and disease, which we are keen to explore in depth over the coming years,” concludes Dr. Emili.

    See the full article here .

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    About Phys.org in 100 Words

    Phys.org™ (formerly Physorg.com) is a leading web-based science, research and technology news service which covers a full range of topics. These include physics, earth science, medicine, nanotechnology, electronics, space, biology, chemistry, computer sciences, engineering, mathematics and other sciences and technologies. Launched in 2004, Phys.org’s readership has grown steadily to include 1.75 million scientists, researchers, and engineers every month. Phys.org publishes approximately 100 quality articles every day, offering some of the most comprehensive coverage of sci-tech developments world-wide. Quancast 2009 includes Phys.org in its list of the Global Top 2,000 Websites. Phys.org community members enjoy access to many personalized features such as social networking, a personal home page set-up, RSS/XML feeds, article comments and ranking, the ability to save favorite articles, a daily newsletter, and other options.

  • richardmitnick 7:57 am on August 25, 2015 Permalink | Reply
    Tags: , , Genetics,   

    From phys.org: “Genetic overlapping in multiple autoimmune diseases may suggest common therapies” 


    August 24, 2015
    No Writer Credit

    DNA double helix. Credit: public domain

    Scientists who analyzed the genes involved in 10 autoimmune diseases that begin in childhood have discovered 22 genome-wide signals shared by two or more diseases. These shared gene sites may reveal potential new targets for treating many of these diseases, in some cases with existing drugs already available for non-autoimmune disorders.

    Autoimmune diseases, such as type 1 diabetes, Crohn’s disease, and juvenile idiopathic arthritis, collectively affect 7 to 10 percent of the population in the Western Hemisphere.

    “Our approach did more than finding genetic associations among a group of diseases,” said study leader, Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children’s Hospital of Philadelphia (CHOP). “We identified genes with a biological relevance to these diseases, acting along gene networks and pathways that may offer very useful targets for therapy.”

    The paper appears online today in Nature Medicine.

    The international study team performed a meta-analysis, including a case-control study of 6,035 subjects with automimmune disease and 10,700 controls, all of European ancestry. The study’s lead analyst, Yun (Rose) Li, an M.D./Ph.D. graduate student at the University of Pennsylvania and the Center for Applied Genomics, mentored by Hakonarson and his research team, applied highly innovative and integrative approaches in supporting the study of pathogenic roles of the genes uncovered across multiple diseases.

    The research encompassed 10 clinically distinct autoimmune diseases with onset during childhood: type 1 diabetes, celiac disease, juvenile idiopathic arthritis, common variable immunodeficiency disease, systemic lupus erythematosus, Crohn’s disease, ulcerative colitis, psoriasis, autoimmune thyroiditis and ankylosing spondylitis.

    Because many of these diseases run in families and because individual patients often have more than one autoimmune condition, clinicians have long suspected these conditions have shared genetic predispositions. Previous genome-wide association studies have identified hundreds of susceptibility genes among autoimmune diseases, largely affecting adults.

    The current research was a systematic analysis of multiple pediatric-onset diseases simultaneously. The study team found 27 genome-wide loci, including five novel loci, among the diseases examined. Of those 27 signals, 22 were shared by at least two of the autoimmune diseases, and 19 of them were shared by at least three of them.

    Many of the gene signals the investigators discovered were on biological pathways functionally linked to cell activation, cell proliferation and signaling systems important in immune processes. One of the five novel signals, near the CD40LG gene, was especially compelling, said Hakonarson, who added, “That gene encodes the ligand for the CD40 receptor, which is associated with Crohn’s disease, ulcerative colitis and celiac disease. This ligand may represent another promising drug target in treating these diseases.”

    Many of the 27 gene signals the investigators uncovered have a biological relevance to autoimmune disease processes, Hakonarson said. “Rather than looking at overall gene expression in all cells, we focused on how these genes upregulated gene expression in specific cell types and tissues, and found patterns that were directly relevant to specific diseases. For instance, among several of the diseases, we saw genes with stronger expression in B cells. Looking at diseases such as lupus or juvenile idiopathic arthritis, which feature dysfunctions in B cells, we can start to design therapies to dial down over-expression in those cells.”

    He added that “the level of granularity the study team uncovered offers opportunities for researchers to better target gene networks and pathways in specific autoimmune diseases, and perhaps to fine tune and expedite drug development by repurposing existing drugs, based on our findings.”

    More information: Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases, Nature Medicine, published online Aug. 24, 2015. doi.org/10.1038/nm.3933

    See the full article here.

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    About Phys.org in 100 Words

    Phys.org™ (formerly Physorg.com) is a leading web-based science, research and technology news service which covers a full range of topics. These include physics, earth science, medicine, nanotechnology, electronics, space, biology, chemistry, computer sciences, engineering, mathematics and other sciences and technologies. Launched in 2004, Phys.org’s readership has grown steadily to include 1.75 million scientists, researchers, and engineers every month. Phys.org publishes approximately 100 quality articles every day, offering some of the most comprehensive coverage of sci-tech developments world-wide. Quancast 2009 includes Phys.org in its list of the Global Top 2,000 Websites. Phys.org community members enjoy access to many personalized features such as social networking, a personal home page set-up, RSS/XML feeds, article comments and ranking, the ability to save favorite articles, a daily newsletter, and other options.

  • richardmitnick 4:24 pm on July 19, 2015 Permalink | Reply
    Tags: , , , Genetics,   

    From WIRED: “Chemists Invent New Letters for Nature’s Genetic Alphabet” 

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    Emily Singer

    Olena Shmahalo/Quanta Magazine

    DNA stores our genetic code in an elegant double helix.

    The structure of the DNA double helix. The atoms in the structure are colour-coded by element and the detailed structure of two base pairs are shown in the bottom right.

    But some argue that this elegance is overrated. “DNA as a molecule has many things wrong with it,” said Steven Benner, an organic chemist at the Foundation for Applied Molecular Evolution in Florida.

    Nearly 30 years ago, Benner sketched out better versions of both DNA and its chemical cousin RNA, adding new letters and other additions that would expand their repertoire of chemical feats.

    A hairpin loop from a pre-mRNA. Highlighted are the nucleobases (green) and the ribose-phosphate backbone (blue). Note that this is a single strand of RNA that folds back upon itself.

    He wondered why these improvements haven’t occurred in living creatures. Nature has written the entire language of life using just four chemical letters: G, C, A and T. Did our genetic code settle on these four nucleotides for a reason? Or was this system one of many possibilities, selected by simple chance? Perhaps expanding the code could make it better.

    Benner’s early attempts at synthesizing new chemical letters failed. But with each false start, his team learned more about what makes a good nucleotide and gained a better understanding of the precise molecular details that make DNA and RNA work. The researchers’ efforts progressed slowly, as they had to design new tools to manipulate the extended alphabet they were building. “We have had to re-create, for our artificially designed DNA, all of the molecular biology that evolution took 4 billion years to create for natural DNA,” Benner said.

    Now, after decades of work, Benner’s team has synthesized artificially enhanced DNA that functions much like ordinary DNA, if not better. In two papers published in the Journal of the American Chemical Society last month, the researchers have shown that two synthetic nucleotides called P and Z fit seamlessly into DNA’s helical structure, maintaining the natural shape of DNA. Moreover, DNA sequences incorporating these letters can evolve just like traditional DNA, a first for an expanded genetic alphabet.

    The new nucleotides even outperform their natural counterparts. When challenged to evolve a segment that selectively binds to cancer cells, DNA sequences using P and Z did better than those without.

    “When you compare the four-nucleotide and six-nucleotide alphabet, the six-nucleotide version seems to have won out,” said Andrew Ellington, a biochemist at the University of Texas, Austin, who was not involved in the study.

    Benner has lofty goals for his synthetic molecules. He wants to create an alternative genetic system in which proteins—intricately folded molecules that perform essential biological functions—are unnecessary. Perhaps, Benner proposes, instead of our standard three-component system of DNA, RNA and proteins, life on other planets evolved with just two.

    Better Blueprints for Life

    The primary job of DNA is to store information. Its sequence of letters contains the blueprints for building proteins. Our current four-letter alphabet encodes 20 amino acids, which are strung together to create millions of different proteins. But a six-letter alphabet could encode as many as 216 possible amino acids and many, many more possible proteins.

    Expanding the genetic alphabet dramatically expands the number of possible amino acids and proteins that cells can build, at least in theory. The existing four-letter alphabet produces 20 amino acids (small circle) while a six-letter alphabet could produce 216 possible amino acids. Olena Shmahalo/Quanta Magazine

    Why nature stuck with four letters is one of biology’s fundamental questions. Computers, after all, use a binary system with just two “letters”—0s and 1s. Yet two letters probably aren’t enough to create the array of biological molecules that make up life. “If you have a two-letter code, you limit the number of combinations you get,” said Ramanarayanan Krishnamurthy, a chemist at the Scripps Research Institute in La Jolla, Calif.

    On the other hand, additional letters could make the system more error prone. DNA bases come in pairs—G pairs with C and A pairs with T. It’s this pairing that endows DNA with the ability to pass along genetic information. With a larger alphabet, each letter has a greater chance of pairing with the wrong partner, and new copies of DNA might harbor more mistakes. “If you go past four, it becomes too unwieldy,” Krishnamurthy said.

    But perhaps the advantages of a larger alphabet can outweigh the potential drawbacks. Six-letter DNA could densely pack in genetic information. And perhaps six-letter RNA could take over some of the jobs now handled by proteins, which perform most of the work in the cell.

    Proteins have a much more flexible structure than DNA and RNA and are capable of folding into an array of complex shapes. A properly folded protein can act as a molecular lock, opening a chamber only for the right key. Or it can act as a catalyst, capturing and bringing together different molecules for chemical reactions.

    Adding new letters to RNA could give it some of these abilities. “Six letters can potentially fold into more, different structures than four letters,” Ellington said.

    Back when Benner was sketching out ideas for alternative DNA and RNA, it was this potential that he had in mind. According to the most widely held theory of life’s origins, RNA once performed both the information-storage job of DNA and the catalytic job of proteins. Benner realized that there are many ways to make RNA a better catalyst.

    “With just these little insights, I was able to write down the structures that are in my notebook as alternatives that would make DNA and RNA better,” Benner said. “So the question is: Why did life not make these alternatives? One way to find out was to make them ourselves, in the laboratory, and see how they work.”

    Steven Benner’s lab notebook from 1985 outlining plans to synthesize “better” DNA and RNA by adding new chemical letters. Courtesy of Steven Benner

    It’s one thing to design new codes on paper, and quite another to make them work in real biological systems. Other researchers have created their own additions to the genetic code, in one case even incorporating new letters into living bacteria. But these other bases fit together a bit differently from natural ones, stacking on top of each other rather than linking side by side. This can distort the shape of DNA, particularly when a number of these bases cluster together. Benner’s P-Z pair, however, is designed to mimic natural bases.

    One of the new papers by Benner’s team shows that Z and P are yoked together by the same chemical bond that ties A to T and C to G. (This bond is known as Watson-Crick pairing, after the scientists who discovered DNA’s structure.) Millie Georgiadis, a chemist at Indiana University-Purdue University Indianapolis, along with Benner and other collaborators, showed that DNA strands that incorporate Z and P retain their proper helical shape if the new letters are strung together or interspersed with natural letters.

    “This is very impressive work,” said Jack Szostak, a chemist at Harvard University who studies the origin of life, and who was not involved in the study. “Finding a novel base pair that does not grossly disrupt the double-helical structure of DNA has been quite difficult.”

    The team’s second paper demonstrates how well the expanded alphabet works. Researchers started with a random library of DNA strands constructed from the expanded alphabet and then selected the strands that were able to bind to liver cancer cells but not to other cells. Of the 12 successful binders, the best had Zs and Ps in their sequences, while the weakest did not.

    “More functionality in the nucleobases has led to greater functionality in nucleic acids themselves,” Ellington said. In other words, the new additions appear to improve the alphabet, at least under these conditions.

    But additional experiments are needed to determine how broadly that’s true. “I think it will take more work, and more direct comparisons, to be sure that a six-letter version generally results in ‘better’ aptamers [short DNA strands] than four-letter DNA,” Szostak said. For example, it’s unclear whether the six-letter alphabet triumphed because it provided more sequence options or because one of the new letters is simply better at binding, Szostak said.

    Benner wants to expand his genetic alphabet even further, which could enhance its functional repertoire. He’s working on creating a 10- or 12-letter system and plans to move the new alphabet into living cells. Benner’s and others’ synthetic molecules have already proved useful in medical and biotech applications, such as diagnostic tests for HIV and other diseases. Indeed, Benner’s work helped to found the burgeoning field of synthetic biology, which seeks to build new life, in addition to forming useful tools from molecular parts.

    Why Life’s Code Is Limited

    Benner’s work and that of other researchers suggests that a larger alphabet has the capacity to enhance DNA’s function. So why didn’t nature expand its alphabet in the 4 billion years it has had to work on it? It could be because a larger repertoire has potential disadvantages. Some of the structures made possible by a larger alphabet might be of poor quality, with a greater risk of misfolding, Ellington said.

    Nature was also effectively locked into the system at hand when life began. “Once [nature] has made a decision about which molecular structures to place at the core of its molecular biology, it has relatively little opportunity to change those decisions,” Benner said. “By constructing unnatural systems, we are learning not only about the constraints at the time that life first emerged, but also about constraints that prevent life from searching broadly within the imagination of chemistry.”

    The genetic code—made up of the four letters, A, T, G and C—stores the blueprint for proteins. DNA is first transcribed into RNA and then translated into proteins, which fold into specific shapes. Olena Shmahalo/Quanta Magazine

    Benner aims to make a thorough search of that chemical space, using his discoveries to make new and improved versions of both DNA and RNA. He wants to make DNA better at storing information and RNA better at catalyzing reactions. He hasn’t shown directly that the P-Z base pairs do that. But both bases have the potential to help RNA fold into more complex structures, which in turn could make proteins better catalysts. P has a place to add a “functional group,” a molecular structure that helps folding and is typically found in proteins. And Z has a nitro group, which could aid in molecular binding.

    In modern cells, RNA acts as an intermediary between DNA and proteins. But Benner ultimately hopes to show that the three-biopolymer system—DNA, RNA and proteins—that exists throughout life on Earth isn’t essential. With better-engineered DNA and RNA, he says, perhaps proteins are unnecessary.

    Indeed, the three-biopolymer system may have drawbacks, since information flows only one way, from DNA to RNA to proteins. If a DNA mutation produces a more efficient protein, that mutation will spread slowly, as organisms without it eventually die off.

    What if the more efficient protein could spread some other way, by directly creating new DNA? DNA and RNA can transmit information in both directions. So a helpful RNA mutation could theoretically be transformed into beneficial DNA. Adaptations could thus lead directly to changes in the genetic code.

    Benner predicts that a two-biopolymer system would evolve faster than our own three-biopolymer system. If so, this could have implications for life on distant planets. “If we find life elsewhere,” he said, “it would likely have the two-biopolymer system.”

    See the full article here.

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  • richardmitnick 1:40 pm on April 22, 2015 Permalink | Reply
    Tags: , Genetics,   

    From Princeton: “Decoding the Cell’s Genetic Filing System (Nature Chemistry)” 

    Princeton University
    Princeton University

    April 22, 2015
    Tien Nguyen

    Source: Nature Chemistry

    A fully extended strand of human DNA measures about five feet in length. Yet it occupies a space just one-tenth of a cell by wrapping itself around histones—spool-like proteins—to form a dense hub of information called chromatin.

    Access to these meticulously packed genes is regulated by post-translational modifications, chemical changes to the structure of histones that act as on-off signals for gene transcription. Mistakes or mutations in histones can cause diseases such as glioblastoma, a devastating pediatric brain cancer.

    Researchers at Princeton University have developed a facile method to introduce non-native chromatin into cells to interrogate these signaling pathways. Published on April 6 in the journal Nature Chemistry, this work is the latest chemical contribution from the Muir lab towards understanding nature’s remarkable information indexing system.

    Tom Muir, the Van Zandt Williams, Jr. Class of ’65 Professor of Chemistry, began investigating transcriptional pathways in the so-called field of epigenetics almost a decade earlier. Deciphering such a complex and dynamic system posed a formidable challenge, but his research lab was undeterred. “It’s better to fail at something important than to succeed at something trivial,” he said.

    Muir recognized the value of introducing chemical approaches to epigenetics to complement early contributions that came mainly from molecular biologists and geneticists. If epigenetics was like a play, he said, molecular biology and genetics could identify the characters but chemistry was needed to understand the subplots.

    These subplots, or post-translational modifications of histones, of which there are more than 100, can occur cooperatively and simultaneously. Traditional methods to probe post-translational modifications involved synthesizing modified histones one at a time, which was a very slow process that required large amounts of biological material.

    Last year, the Muir group introduced a method that would massively accelerate this process. The researchers generated a library of 54 nucleosomes—single units of chromatin, like pearls on a necklace—encoded with DNA-barcodes, unique genetic tags that can be easily identified. Published in the journal Nature Methods, the high throughput method required only microgram amounts of each nucleosome to run approximately 4,500 biochemical assays.

    “The speed and sensitivity of the assay was shocking,” Muir said. Each biochemical assay involved treatment of the DNA-barcoded nucleosome with a writer, reader or nuclear extract, to reveal a particular binding preference of the histone. The products were then isolated using a technique called chromatin immunoprecipitation and characterized by DNA sequencing, essentially an ordered readout of the nucleotides.

    “There have been incredible advances in genetic sequencing over the last 10 years that have made this work possible,” said Manuel Müller, a postdoctoral researcher in the Muir lab and co-author on the Nature Methods article.

    Schematic of approach using split inteins

    With this method, researchers could systematically interrogate the signaling system to propose mechanistic pathways. But these mechanistic insights would remain hypotheses unless they could be validated in vivo, meaning inside the cellular environment.

    The only method for modifying histones in vivo was extremely complicated and specific, said Yael David, a postdoctoral researcher in the Muir lab and lead author on the recent Nature Chemistry study that demonstrated a new and easily customizable approach.

    The method relied on using ultra-fast split inteins, protein fragments that have a great affinity for one another. First, one intein fragment was attached to a modified histone, by encoding it into a cell. Then, the other intein fragment was synthetically fused to a label, which could be a small protein tag, fluorophore or even an entire protein like ubiquitin.

    Within minutes of being introduced into the cell, the labeled intein fragment bound to the histone intein fragment. Then like efficient and courteous matchmakers, the inteins excised themselves and created a new bond between the label and modified histone. “It’s really a beautiful way to engineer proteins in a cell,” David said.

    Regions of the histone may be loosely or tightly packed, depending on signals from the cell indicating whether or not to transcribe a gene. By gradually lowering the amount of labeled intein introduced, the researchers could learn about the structure of chromatin and tease out which areas were more accessible than others.

    Future plans in the Muir lab will employ these methods to ask specific biological questions, such as whether disease outcomes can be altered by manipulating signaling pathway. “Ultimately, we’re developing methods at the service of biological questions,” Muir said.

    Read the articles:

    Nguyen, U.T.T.; Bittova, L.; Müller, M.; Fierz, B.; David, Y.; Houck-Loomis, B.; Feng, V.; Dann, G.P.; Muir, T.W. Accelerated chromatin biochemistry using DNA-barcoded nucleosome libraries. Nature Methods, 2014, 11, 834.

    David, Y.; Vila-Perelló, M; Verma, S.; Muir, T.W. Chemical tagging and customizing of cellular chromatin states using ultrafast trans-splicing inteins. Nature Chemistry, Advance online publication, April 6, 2015.

    See the full article here.

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    About Princeton: Overview

    Princeton University is a vibrant community of scholarship and learning that stands in the nation’s service and in the service of all nations. Chartered in 1746, Princeton is the fourth-oldest college in the United States. Princeton is an independent, coeducational, nondenominational institution that provides undergraduate and graduate instruction in the humanities, social sciences, natural sciences and engineering.

    As a world-renowned research university, Princeton seeks to achieve the highest levels of distinction in the discovery and transmission of knowledge and understanding. At the same time, Princeton is distinctive among research universities in its commitment to undergraduate teaching.

    Today, more than 1,100 faculty members instruct approximately 5,200 undergraduate students and 2,600 graduate students. The University’s generous financial aid program ensures that talented students from all economic backgrounds can afford a Princeton education.

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