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Stem cells from teeth can make neuron-like cells and networks

Stem cells from teeth can make neuron-like cells and networks | Amazing Science | Scoop.it

University of Adelaide researchers have discovered that stem cells taken from teeth can grow to form complex networks of neuron-like cells, suggesting a possible therapy for stroke. Although these cells haven’t developed into fully fledged neurons, researchers believe it’s just a matter of time and the right conditions for it to happen.


“Stem cells from teeth have great potential to grow into new brain or nerve cells, and this could potentially assist with treatments of brain disorders, such as stroke,” says Kylie Ellis, PhD, Commercial Development Manager with the University’s commercial arm, Adelaide Research & Innovation (ARI).


The stem cells expressed neuronal cytoplasmic proteins, neurotransmitter-specific markers, and functional voltage-gated L-type Ca2+ channels, but not spontaneous action potentials. “The reality is, treatment options available to the thousands of stroke patients every year are limited,” Ellis says. “The primary drug treatment available must be administered within hours of a stroke and many people don’t have access within that timeframe, because they often can’t seek help for some time after the attack.


“Ultimately, we want to be able to use a patient’s own stem cells for tailor-made brain therapy that doesn’t have the host rejection issues commonly associated with cell-based therapies. Another advantage is that dental pulp stem cell therapy may provide a treatment option available months or even years after the stroke has occurred,” she says.


“We can do this by providing an environment for the cells that is as close to a normal brain environment as possible, so that instead of becoming cells for teeth they become brain cells,” Ellis says.


“What we developed wasn’t identical to normal neurons, but the new cells shared very similar properties to neurons. They also formed complex networks and communicated through simple electrical activity, like you might see between cells in the developing brain.”


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New Single-Cell Technologies, Scientists Create Comprehensive Map of Human B Cell Development

New Single-Cell Technologies, Scientists Create Comprehensive Map of Human B Cell Development | Amazing Science | Scoop.it

In a new paper published in the journal Cell, a team of researchers led by Dana Pe’er at Columbia University and Garry Nolan at Stanford University describes a powerful new method for mapping cellular development at the single cell level. By combining emerging technologies for studying single cells with a new, advanced computational algorithm, they have designed a novel approach for mapping development and created the most comprehensive map ever made of human B cell development. Their approach will greatly improve researchers’ ability to investigate development in cells of all types, make it possible to identify rare aberrations in development that lead to disease, and ultimately help to guide the next generation of research in regenerative medicine.


Pointing out why being able to generate these maps is an important advance, Dr. Pe’er, an associate professor in the Columbia University Department of Systems Biology and Department of Biological Sciences, explains, “There are so many diseases that result from malfunctions in the molecular programs that control the development of our cell repertoire and so many rare, yet important, regulatory cell types that we have yet to discover. We can only truly understand what goes wrong in these diseases if we have a complete map of the progression in normal development. Such maps will also act as a compass for regenerative medicine, because it’s very difficult to grow something if you don’t know how it develops in nature. For the first time, our method makes it possible to build a high-resolution map, at the single cell level, that can guide these kinds of research.”


Just as genome sequencing transformed how biology was studied in the previous decade, new technologies for analyzing the molecular properties of single cells are currently revolutionizing the kinds of questions many biologists are asking. Dr. Pe’er sees single-cell approaches as an important step beyond genomics. “DNA sequencing can identify genes and mutations, but often they are not studied in context,” she points out. “With single-cell approaches, we can map the cells where the action actually happens and what the genes are doing inside them. Single-cell mapping will do for development what genome sequencing has done for genetics.”


Investigators in the Nolan lab used mass cytometry to profile 44 markers in a cohort of approximately 200,000 healthy immune cells that were gathered from one such sample. In each cell they measured cell surface markers that help identify what type of cell it is, as well as markers inside the cell that can reveal what the cell is doing, including markers for signaling, the cell cycle, apoptosis, and genome rearrangement.

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Fast way to measure DNA repair – some people's DNA gets repaired 10 times faster than others

Fast way to measure DNA repair – some people's DNA gets repaired 10 times faster than others | Amazing Science | Scoop.it
Test analyzing cells’ ability to fix different kinds of broken DNA could help doctors predict cancer risk.


Our DNA is under constant attack from many sources, including environmental pollutants, ultraviolet light, and radiation. Fortunately, cells have several major DNA repair systems that can fix this damage, which may lead to cancer and other diseases if not mended.


The effectiveness of these repair systems varies greatly from person to person; scientists believe that this variability may explain why some people get cancer while others exposed to similar DNA-damaging agents do not. A team of MIT researchers has now developed a test that can rapidly assess several of these repair systems, which could help determine individuals’ risk of developing cancer and help doctors predict how a given patient will respond to chemotherapy drugs.


The new test, described in the Proceedings of the National Academy of Sciences the week of April 21, can analyze four types of DNA repair capacity simultaneously, in less than 24 hours. Previous tests have been able to evaluate only one system at a time.


“All of the repair pathways work differently, and the existing technology to measure each of those pathways is very different for each one. It takes expertise, it’s time-consuming, and it’s labor-intensive,” says Zachary Nagel, an MIT postdoc and lead author of the PNAS paper. “What we wanted to do was come up with one way of measuring all DNA repair pathways at the same time so you have a single readout that’s easy to measure.”


The research team, led by professor Leona Samson, used this approach to measure DNA repair in a type of immortalized human blood cells called lymphoblastoid cells, taken from 24 healthy people. They found a huge range of variability, especially in one repair system where some people’s cells were more than 10 times more efficient than others.


“None of the cells came out looking the same. They each have their own spectrum of what they can repair well and what they don’t repair well. It’s like a fingerprint for each person,” says Samson, who is the Uncas and Helen Whitaker Professor, an American Cancer Society Professor, and a member of MIT’s departments of biological engineering and of biology, Center for Environmental Health Sciences, and Koch Institute for Integrative Cancer Research.


With the new test, the MIT team can measure how well cells repair the most common DNA lesions, including single-strand breaks, double-strand breaks, mismatches, and the introduction of alkyl groups caused by pollutants such as fuel exhaust and tobacco smoke.


To achieve this, the researchers created five different circular pieces of DNA, four of which carry a specific type of DNA damage, also called DNA lesions. Each of these circular DNA strands, or plasmids, also carries a gene for a different colored fluorescent protein. In some cases, the DNA lesions prevent those genes from being expressed, so when the DNA is successfully repaired, the cell begins to produce the fluorescent protein. In others, repairing the DNA lesion turns the fluorescent gene off.


By introducing these plasmids into cells and reading the fluorescent output, scientists can determine how efficiently each kind of lesion has been repaired. In theory, more than five plasmids could go into each cell, but the researchers limited each experiment to five reporter plasmids to avoid potential overlap among colors. To overcome that limitation, the researchers are also developing an alternative tactic that involves sequencing the messenger RNA produced by cells when they copy the plasmid genes, instead of measuring fluorescence.

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Researchers Clone Cells From Two Adult Men

Researchers Clone Cells From Two Adult Men | Amazing Science | Scoop.it
After years of failed attempts, researchers have successfully generated stem cells from adults. The process could provide a new way for scientists to generate healthy replacements for diseased or damaged cells in patients


After years of failed attempts, researchers have finally generated stem cells from adults using the same cloning technique that produced Dolly the sheep in 1996.


A previous claim that Korean investigators had succeeded in the feat turned out to be fraudulent. Then last year, a group at Oregon Health & Science University generated stem cells using the Dolly technique, but with cells from fetuses and infants.In this case, cells from a 35-year-old man and a 75-year-old man were used to generate two separate lines of stem cells.

The process, known as nuclear transfer, involves taking the DNA from a donor and inserting it into an egg that has been stripped of its DNA. The resulting hybrid is stimulated to fuse and start dividing; after a few days the “embryo” creates a lining of stem cells that are destined to develop into all of the cells and tissues in the human body. Researchers extract these cells and grow them in the lab, where they are treated with the appropriate growth factors and other agents to develop into specific types of cells, like neurons, muscle, or insulin-producing cells.

Reporting in the journal Cell Stem Cell, Dr. Robert Lanza, chief scientific officer at biotechnology company Advanced Cell Technology, and his colleagues found that tweaking the Oregon team’s process was the key to success with reprogramming the older cells. Like the earlier team, Lanza’s group used caffeine to prevent the fused egg from dividing prematurely. Rather than leaving the egg with its newly introduced DNA for 30 minutes before activating the dividing stage, they let the eggs rest for about two hours. This gave the DNA enough time to acclimate to its new environment and interact with the egg’s development factors, which erased each of the donor cell’s existing history and reprogrammed it to act like a brand new cell in an embryo.


The team, which included an international group of stem cell scientists, used 77 eggs from four different donors. They tested their new method by waiting for 30 minutes before activating 38 of the resulting embryos, and waiting two hours before triggering 39 of them. None of the 38 developed into the next stage, while two of the embryos getting extended time did. “There is a massive molecular change occurring. You are taking a fully differentiated cell, and you need to have the egg do its magic,” says Lanza. “You need to extend the reprogramming time before you can force the cell to divide.”


While a 5% efficiency may not seem laudable, Lanza says that it’s not so bad given that the stem cells appear to have had their genetic history completely erased and returned to that of a blank slate. “This procedure works well, and works with adult cells,” says Lanza.


The results also teach stem cell scientists some important lessons. First, that the nuclear transfer method that the Oregon team used is valid, and that with some changes it can be replicated using older adult cells. “It looks like the protocols we described are real, they are universal, they work in different hands, in different labs and with different cells,” says Shoukhrat Mitalopov, director of the center for embryonic cell and gene therapy at Oregon Health & Science University, and lead investigator of that study.


VIDEO: Breakthrough in Cloning Human Stem Cells: Explainer


MORE: Stem-Cell Research: The Quest Resumes

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Innovative Genomics Initiative launched around CRISPR-CAS9 genome editing technology

Innovative Genomics Initiative launched around CRISPR-CAS9 genome editing technology | Amazing Science | Scoop.it
The University of California, Berkeley, and UC San Francisco are launching the Innovative Genomics Initiative (IGI) to lead a revolution in genetic engineering based on a new technology already generating novel strategies for gene therapy and the genetic study of disease.


The Li Ka Shing Foundation has provided a $10 million gift to support the initiative, establishing the Li Ka Shing Center for Genomic Engineering and an affiliated faculty chair at UC Berkeley. The two universities also will provide $2 million in start-up funds.


At the core of the initiative is a revolutionary technology discovered two years ago at UC Berkeley by Jennifer A. Doudna, executive director of the initiative and the new faculty chair. The technology, precision "DNA scissors" referred to as CRISPR/Cas9, has exploded in popularity since it was first published in June 2012 and is at the heart of at least three start-ups and several heavily-attended international meetings. Scientists have referred to it as the "holy grail" of genetic engineering and a "jaw-dropping" breakthrough in the fight against genetic disease. In honor of her discovery and earlier work on RNA, Doudna received last month the Lurie Prize of the Foundation for the National Institutes of Health.


"Professor Doudna's breakthrough discovery in genomic editing is leading us into a new era of possibilities that we could have never before imagined," said Li Ka-shing, chairman of the Li Ka Shing Foundation. "It is a great privilege for my foundation to engage with two world-class public institutions to launch the Innovative Genomics Initiative in this quest for the holy grail to fight genetic diseases."


In the 18 months since the discovery of this technology was announced, more than 125 papers have been published based on the technique. Worldwide, researchers are using Cas9 to investigate the genetic roots of problems as diverse as sickle cell anemia, diabetes, cystic fibrosis, AIDS and depression in hopes of finding new drug targets. Others are adapting the technology to reengineer yeast to produce biofuels and wheat to resist pests and drought.


The new genomic engineering technology significantly cuts down the time it takes researchers to test new therapies. CRISPR/Cas 9 allows the creation in weeks rather than years of animal strains that mimic a human disease, allowing researchers to test new therapies. The technique also makes it quick and easy to knock out genes in human cells or in animals to determine their function, which will speed the identification of new drug targets for diseases.


"We now have a very easy, very fast and very efficient technique for rewriting the genome, which allows us to do experiments that have been impossible before," said Doudna, a professor of molecular and cell biology in the California Institute for Quantitative Biosciences (QB3) and an investigator in the Howard Hughes Medical Institute at UC Berkeley. "We are grateful to Mr. Li Ka-shing for his support of our initiative, which will propel ground-breaking advances in genomic engineering."

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New treatment for hepatitis C "cured" 90% of patients with the infection in 12 weeks, scientists said

New treatment for hepatitis C "cured" 90% of patients with the infection in 12 weeks, scientists said | Amazing Science | Scoop.it

An international study involving 380 patients has seen 90% of patients "cured" of Hepatitis C in the course of 12 weeks. Experts are calling the treatment a turning point in the treatment of the pernicious disease, which wreaks havoc on the livers of those it infects. Too bad it costs over $80,000 for a course of treatment.


The treatment goes by the name of Sovaldi and was created by Gilead Sciences. The BBC has a good rundown of the study:  Researchers at the University of Texas Health Science Centre tested the new oral drug in 380 patients at 78 centres in Spain, Germany, England and the US in 2013. Two studies were carried out, one in patients for 12 weeks, and another, for 24 weeks. The patients had liver cirrhosis, indicating an advanced form of the virus.


After 12 weeks, 191 of 208 patients no longer had hepatitis C, which increased to 165 of 172 patients, or 96%, after 24 weeks. Lead researcher, Dr Fred Poordad said: "It is fantastic. I am so excited for the patients. There is finally hope for their future." He said the drug worked by targeting the protein that makes hepatitis C and stopping it from replicating. "Eventually the virus is extinguished," he said.


All excellent news, of course. The bad news is that the treatment is ridiculously expensive. Gilead has proposed a global, tiered pricing system that is based on each country's per capita gross national income. According to Reuters, the cost for a full course of treatment in the U.K. is about $57,000; the price in Germany around $66,000; and the price in America around $84,000. That's close to $1,000 a pill for U.S. residents. And in Egypt and other developing countries, the bill amounts to $900 - a whooping 99 percent less than in the U.S. The company's price scheme has been called "unreasonably high" and "obscene" by care providers like Kaiser Permanente and Molina Healthcare, respectively. Even Congress asked Gilead to justify the price of their drug.


But Gilead has stood firm on its price plan, arguing that their drug is worth the cost because it works faster and more effectively than anything else. Fortunately, it looks like they'll finally have some competition in the coming months.

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Ahmed Atef's comment, April 14, 2:43 AM
Is there any technical information for this drug. What is the technology for targeting.
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Duke bioengineered artificial muscle can self-heal inside the body

Duke bioengineered artificial muscle can self-heal inside the body | Amazing Science | Scoop.it
Biomedical engineers have grown living skeletal muscle that looks a lot like the real thing. It contracts powerfully and rapidly, integrates into mice quickly, and for the first time, demonstrates the ability to heal itself both inside the laboratory and inside an animal.


The study conducted at Duke University tested the bioengineered muscle by literally watching it through a window on the back of living mouse. The novel technique allowed for real-time monitoring of the muscle’s integration and maturation inside a living, walking animal.


Both the lab-grown muscle and experimental techniques are important steps toward growing viable muscle for studying diseases and treating injuries, said Nenad Bursac, associate professor of biomedical engineering at Duke. The results were published on March 31, 2014 in the Proceedings of the National Academy of Sciences Early Edition.


“The muscle we have made represents an important advance for the field,” Bursac said. “It’s the first time engineered muscle has been created that contracts as strongly as native neonatal skeletal muscle.” Through years of perfecting their techniques, a team led by Bursac and graduate student Mark Juhas discovered that preparing better muscle requires two things—well-developed contractile muscle fibers and a pool of muscle stem cells, known as satellite cells.


Every muscle has satellite cells on reserve, ready to activate upon injury and begin the regeneration process. The key to the team’s success was successfully creating the micro-environments—called niches—where these stem cells await their call to duty.


“Simply implanting satellite cells or less-developed muscle doesn’t work as well,” said Juhas. “The well-developed muscle we made provides niches for satellite cells to live in, and, when needed, to restore the robust musculature and its function.”


By genetically modifying the muscle fibers to produce fluorescent flashes during calcium spikes—which cause muscle to contract— the researchers could watch the flashes become brighter as the muscle grew stronger.


“We could see and measure in real time how blood vessels grew into the implanted muscle fibers, maturing toward equaling the strength of its native counterpart,” said Juhas.


The engineers are now beginning work to see if their biomimetic muscle can be used to repair actual muscle injuries and disease.

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Liquid biopsy blood test could provide rapid, accurate method of detecting solid cancers, study finds

Liquid biopsy blood test could provide rapid, accurate method of detecting solid cancers, study finds | Amazing Science | Scoop.it

A blood sample could one day be enough to diagnose many types of solid cancers, or to monitor the amount of cancer in a patient’s body and responses to treatment. Previous versions of the approach, which relies on monitoring levels of tumor DNA circulating in the blood, have required cumbersome and time-consuming steps to customize it to each patient or have not been sufficiently sensitive.


Now, researchers at the Stanford University School of Medicine have devised a way to quickly bring the technique to the clinic. Their approach, which should be broadly applicable to many types of cancers, is highly sensitive and specific. With it they were able to accurately identify about 50 percent of people in the study with stage-1 lung cancer and all patients whose cancers were more advanced.


“We set out to develop a method that overcomes two major hurdles in the circulating tumor DNA field,” said Maximilian Diehn, MD, PhD, assistant professor of radiation oncology. “First, the technique needs to be very sensitive to detect the very small amounts of tumor DNA present in the blood. Second, to be clinically useful it’s necessary to have a test that works off the shelf for the majority of patients with a given cancer.”


Even in the absence of treatment, cancer cells are continuously dividing and dying. As they die, they release DNA into the bloodstream, like tiny genetic messages in a bottle. Learning to read these messages — and to pick out the one in 1,000 or 10,000 that come from a cancer cell — can allow clinicians to quickly and noninvasively monitor the volume of tumor, a patient’s response to therapy and even how the tumor mutations evolve over time in the face of treatment or other selective pressures.


“The vast majority of circulating DNA is from normal, non-cancerous cells, even in patients with advanced cancer,” Bratman said. “We needed a comprehensive strategy for isolating the circulating DNA from blood and detecting the rare, cancer-associated mutations. To boost the sensitivity of the technique, we optimized methods for extracting, processing and analyzing the DNA.


The researchers’ technique, which they have dubbed CAPP-Seq, for Cancer Personalized Profiling by deep Sequencing, is sensitive enough to detect just one molecule of tumor DNA in a sea of 10,000 healthy DNA molecules in the blood. Although the researchers focused on patients with non-small-cell lung cancer (which includes most lung cancers, including adenocarcinomas, squamous cell carcinoma and large cell carcinoma), the approach should be widely applicable to many different solid tumors throughout the body. It’s also possible that it could one day be used not just to track the progress of a previously diagnosed patient, but also to screen healthy or at-risk populations for signs of trouble.


Tumor DNA differs from normal DNA by virtue of mutations in the nucleotide sequence. Some of the mutations are thought to be cancer drivers, responsible for initiating the uncontrolled cell growth that is the hallmark of the disease. Others accumulate randomly during repeated cell division. These secondary mutations can sometimes confer resistance to therapy; even a few tumor cells with these types of mutations can expand rapidly in the face of seemingly successful treatment.

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Researchers have genetically engineered trees that will be easier to break down to produce paper and biofuel

Researchers have genetically engineered trees that will be easier to break down to produce paper and biofuel | Amazing Science | Scoop.it
Researchers have genetically engineered trees that will be easier to break down to produce paper and biofuel, a breakthrough that will mean using fewer chemicals, less energy and creating fewer environmental pollutants.


"One of the largest impediments for the pulp and paper industry as well as the emerging biofuel industry is a polymer found in wood known as lignin," says Shawn Mansfield, a professor of Wood Science at the University of British Columbia.


Lignin makes up a substantial portion of the cell wall of most plants and is a processing impediment for pulp, paper and biofuel. Currently the lignin must be removed, a process that requires significant chemicals and energy and causes undesirable waste.


Researchers used genetic engineering to modify the lignin to make it easier to break down without adversely affecting the tree's strength.

"We're designing trees to be processed with less energy and fewer chemicals, and ultimately recovering more wood carbohydrate than is currently possible," says Mansfield.


Researchers had previously tried to tackle this problem by reducing the quantity of lignin in trees by suppressing genes, which often resulted in trees that are stunted in growth or were susceptible to wind, snow, pests and pathogens.


"It is truly a unique achievement to design trees for deconstruction while maintaining their growth potential and strength." The genetic modification strategy employed in this study could also be used on other plants like grasses to be used as a new kind of fuel to replace petroleum.


Genetic modification can be a contentious issue, but there are ways to ensure that the genes do not spread to the forest. These techniques include growing crops away from native stands so cross-pollination isn't possible; introducing genes to make both the male and female trees or plants sterile; and harvesting trees before they reach reproductive maturity.


In the future, genetically modified trees could be planted like an agricultural crop, not in our native forests. Poplar is a potential energy crop for the biofuel industry because the tree grows quickly and on marginal farmland. Lignin makes up 20 to 25 per cent of the tree.


"We're a petroleum reliant society," says Mansfield. "We rely on the same resource for everything from smartphones to gasoline. We need to diversify and take the pressure off of fossil fuels. Trees and plants have enormous potential to contribute carbon to our society."

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First comprehensive atlas of human gene activity released

First comprehensive atlas of human gene activity released | Amazing Science | Scoop.it

A large international consortium of researchers has produced the first comprehensive, detailed map of the way genes work across the major cells and tissues of the human body. The findings describe the complex networks that govern gene activity, and the new information could play a crucial role in identifying the genes involved with disease.


“Now, for the first time, we are able to pinpoint the regions of the genome that can be active in a disease and in normal activity, whether it’s in a brain cell, the skin, in blood stem cells or in hair follicles,” said Winston Hide, associate professor of bioinformatics and computational biology at Harvard School of Public Health (HSPH) and one of the core authors of the main paper in Nature.


“This is a major advance that will greatly increase our ability to understand the causes of disease across the body.”


The research is outlined in a series of papers published March 27, 2014, two in the journal Nature and 16 in other scholarly journals. The work is the result of years of concerted effort among 250 experts from more than 20 countries as part of FANTOM 5 (Functional Annotation of the Mammalian Genome). The FANTOM project, led by the Japanese institution RIKEN, is aimed at building a complete library of human genes.


Researchers studied human and mouse cells using a new technology called Cap Analysis of Gene Expression (CAGE), developed at RIKEN, to discover how 95% of all human genes are switched on and off. These “switches” — called “promoters” and “enhancers” — are the regions of DNA that manage gene activity. The researchers mapped the activity of 180,000 promoters and 44,000 enhancers across a wide range of human cell types and tissues and, in most cases, found they were linked with specific cell types.


“We now have the ability to narrow down the genes involved in particular diseases based on the tissue cell or organ in which they work,” said Hide. “This new atlas points us to the exact locations to look for the key genetic variants that might map to a disease.”

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Eli Levine's curator insight, March 28, 4:27 PM
There it is. As it is in our genes, so too is it in our individual psyches and societies. Check it out!
Martin Daumiller's curator insight, March 29, 9:27 AM

original article: http://www.nature.com/nature/journal/v507/n7493/full/nature13182.html

 

 

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Technology: With a unique program, the US government has managed to drive the cost of genome sequencing down to $1,000

Technology: With a unique program, the US government has managed to drive the cost of genome sequencing down to $1,000 | Amazing Science | Scoop.it

With a unique program, the US government has managed to drive the cost of genome sequencing down towards a much-anticipated target.


The quest to sequence the first human genome was a massive undertaking. Between 1990 and the publication of a working draft in 2001, more than 200 scientists joined forces in a $3-billion effort to read the roughly 3 billion bases of DNA that comprise our genetic material (International Human Genome Sequencing Consortium Nature 409860921; 2001).


It was a grand but sobering success. The project's advocates had said that it would reveal 'life's instruction book', but in fact it did not make it possible to interpret how the instructions encoded in DNA were transformed into biology. Understanding how DNA actually influences health and disease would require studying examples of the links between genes and biology in thousands, perhaps millions, more people. The dominant technology at the time was Sanger sequencing, an inherently slow, labour-intensive process that works by making copies of the DNA to be sequenced that include chemically modified and fluorescently tagged versions of the molecule's building blocks. One company, Applied Biosystems in Foster City, California, provided the vast majority of the sequencers to a limited number of customers — generally, large government-funded laboratories — and there was little incentive for it to reinvent its core technology.


A $7-million award from the NHGRI allowed the company to commercialize a technology called pyrosequencing, which was the first to begin chipping away at Applied Biosystems' monopoly. The funding commitments also ultimately helped to convince private investors to enter the market. Stephen Turner, founder and chief technology officer of Pacific Biosciences in Menlo Park, California, says that his company's 2005 NHGRI grant of $6.6 million helped to attract subsequent venture-capital funding.


The government program has invested $88 million in technologies based on nanopores and nanogaps. The form of this technology closest to the market involves reading bases as they are threaded through a pore (see Nature 456, 2325; 2008), a method that has long promised to save costs and time by reading DNA while it is processed. It would negate the need for expensive and slow reactions to make lots of copies of the molecule. But solving basic issues, including how to move the DNA through the pore slowly enough, has been a major challenge. The NHGRI has funded work to overcome these hurdles — including $9.3 million given to collaborators of the company now ushering the concept to market, UK-based Oxford Nanopore Technologies (Nature http://doi.org/rvm; 2014).


Sequencing still needs much improvement, especially in terms of quality. For all of Sanger sequencing's high cost, it remains the benchmark for accuracy. And sequencing costs are no longer dropping as quickly as they were a few years ago.


But researchers are optimistic that another technology will emerge to challenge Illumina. Most think, in fact, that the crucial questions for the field will shift away from technology. Now that sequencing is cheap enough to talk about scanning every patient's genome, or at least the protein-coding portion of it, it is still not clear how that information will translate into improved care (Nature http://doi.org/rvq; 2014). These more complex issues will require another great leap in genomic science — one that could make the trouncing of Moore's law seem easy


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Medical microrobots to deliver drugs on demand

Medical microrobots to deliver drugs on demand | Amazing Science | Scoop.it

Advances in micro- and nanoscale engineering in the medical field have led to the development of various robotic designs that one day will allow a new level of minimally invasive medicine. These micro- and nanorobots will be able to reach a targeted area, provide treatments and therapies for a desired duration, measure the effects and, at the conclusion of the treatment, be removed or degrade without causing adverse effects. Ideally, all these tasks would be automated but they could also be performed under the direct supervision and control of an external user.Several approaches have been explored for the wireless actuation of microrobots. Among these, magnetic fields have been the most widely employed strategy for propulsion because they do not require special environmental properties such as conductivity or transparency (for instance: "Artificial nano swimmers", with a video that shows the controlled motions of particles in a magnetic field).


This approach allows for the precise manipulation of magnetic objects toward specific locations, and magnetic fields are biocompatible even at relatively high field strengths (MRI).In a new work, a team of researchers from ETH Zurich and Harvard University (David Mooney's lab) demonstrate that additional intelligence – including sensing and actuation – can be instantiated in these microrobots by selecting appropriate materials and methods for the fabrication process.


"Our work combines the design and fabrication of near infrared light (NIR) responsive hydrogel capsules and biocompatible magnetic microgels with a magnetic manipulation system to perform targeted drug and cell delivery tasks, Dr." Mahmut Selman Sakar, a research scientist in Bradley Nelson's Institute of Robotics and Intelligent Systems at ETH Zurich, tells Nanowerk.Reporting their results in the November 4, 2013 online edition of Advanced Materials ("An Integrated Microrobotic Platform for On-Demand, Targeted Therapeutic Interventions"), first-authored by Sakar's co-researcher Stefano Fusco, the team fabricated an untethered, self-folding, soft microrobotic platform, in which different functionalities are integrated to achieve targeted, on-demand delivery of biological agents.

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Jose Mejia R's comment, March 30, 8:40 AM
TRADUCCION:<br>Los avances en la ingeniería de micro-y nanoescala en el campo de la medicina han conducido al desarrollo de diversos diseños robóticos que un día permitirá un nuevo nivel de la medicina mínimamente invasiva. Estos micro-y nano-robots serán capaces de llegar a un área objetiva, proporcionar tratamientos y terapias para una duración deseada, medir los efectos y, a la conclusión del tratamiento, deberá ser eliminado o degradado sin causar efectos adversos. Lo ideal sería que todas estas tareas se pueden automatizar, pero también pueden ser realizados bajo la supervisión y el control directos de un usuario externo. Varios enfoques se han explorado para el accionamiento inalámbrico de microrobots. Entre éstos, los campos magnéticos han sido la estrategia más ampliamente empleada para la propulsión, ya que no requieren propiedades especiales del medio ambiente tales como la conductividad o la transparencia (por ejemplo: "nadadores nano artificial", con un vídeo que muestra los movimientos controlados de partículas en una magnética campo).<br> <br>Este enfoque permite la manipulación precisa de objetos magnéticos hacia lugares específicos, y los campos magnéticos son biocompatibles, incluso a intensidades de campo relativamente altas (MRI). En un nuevo trabajo, un equipo de investigadores de ETH Zurich y la Universidad de Harvard (el laboratorio de David Mooney) demuestran que con inteligencia adicional - incluyendo detección y actuación - se puede crear instancias de estos microrobots seleccionando materiales y procedimientos para el proceso de fabricación adecuadas.<br><br>"Nuestro trabajo combina el diseño y la fabricación de la luz en el infrarrojo cercano (NIR) cápsulas de hidrogel sensible y microgeles magnéticas biocompatibles con un sistema de manipulación magnética para realizar tareas de administración de drogas y de suministro de células específicas, nos diece el Dr. Mahmut Sakar Selman, un científico de investigación en el Instituto de Bradley Nelson de Robótica y Sistemas Inteligentes en la ETH Zurich. Sus resultados indicados el 04 de noviembre 2013 en la edición en línea de Materiales Avanzados ...
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Rice bioengineers invent light tube array to debug genetic circuits

Rice bioengineers invent light tube array to debug genetic circuits | Amazing Science | Scoop.it

Rice University bioengineers have created a toolkit that uses colored lights and engineered bacteria to bring both mathematical predictability and cut-and-paste simplicity to the world of genetic circuit design.


“Life is controlled by DNA-based circuits, and these are similar to the circuits found in electronic devices like smartphones and computers,” said Rice bioengineer Jeffrey Tabor, the lead researcher on the project.

“A major difference is that electrical engineers measure the signals flowing into and out of electronic circuits as voltage, whereas bioengineers measure genetic circuit signals as genes turning on and off.”


In a paper appearing online in the journal Nature Methods, Tabor and colleagues, including graduate student and lead author Evan Olson, describe a new, ultra high-precision method for creating and measuring gene expression signals in bacteria by combining light-sensing proteins from photosynthetic algae with a simple array of red and green LED lights and standard fluorescent reporter genes.


By varying the timing and intensity of the lights, the researchers were able to control exactly when and how much different genes were expressed.  “Light provides us a powerful new method for reliably measuring genetic circuit activity,” said Tabor, an assistant professor of bioengineering who also teaches in Rice’s Ph.D. program in systems, synthetic and physical biology.


“Our work was inspired by the methods that are used to study electronic circuits. Electrical engineers have tools likeoscilloscopes and function generators that allow them to measure how voltage signals flow through electrical circuits. Those measurements are essential for making multiple circuits work together properly, so that more complex devices can be built. We have used our light-based tools as a biological function generator and oscilloscope in order to similarly analyze genetic circuits.”


If a gene is not “expressed,” it is turned off, and its product is not produced. The bacteria used in Tabor’s study have about 4,000 genes, while humans have about 20,000. The processes of life are coordinated by different combinations and timings of genes turning on and off.

Each component of a genetic circuit acts on the input it receives — which may be one or more gene-expression products from other components — and produces its own gene-expression product as an output.


By linking the right genetic components together, synthetic biologists like Tabor and his students construct genetic circuits that program cells to carry out complex functions, such as counting, having memory, growing into tissues, or diagnosing the signatures of disease in the body.

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Constructing the first designer yeast chromosome opens door to reengineering cells

Constructing the first designer yeast chromosome opens door to reengineering cells | Amazing Science | Scoop.it

Demystifying the intricate underpinnings of genetic processes has been, for many years, a "look, don't touch" endeavor for biologists.  Genetic material and the complex machinery within cells that direct these processes are delicate and complicated. Tampering with these elements has proven difficult, both to alter and track the cells as they pass on their genes to their daughter cells.


Scientists have constructed synthetic bacterium and virus genomes, but have never before succeeded in creating a chromosome from more complex cells like yeast from scratch.  Unlike much simpler bacteria, known to scientists as prokaryotes, the genomes of eukaryotic cells are larger and more complex; their DNA is twisted tightly into multiple tiny packages called chromosomes. Bacteria, on the other hand, usually contain just one compact loop of DNA,  which are often easier to work with and replicate, due to their simpler structure and smaller size. 
 
The synIII chromosome is the first entirely man-made designer chromosome in a complex cell. This marks a major milestone for the international team behind this study, who will use these methods to construct an entire synthetic eukaryotic genome, Sc2.0 (www.syntheticyeast.org), creating a complete artificial yeast genome from scratch to implant into a host cell.
 
S. cerevisiae is used as a model organism by investigators seeking answers about the interactions between genes in more complex cells.  The S. cerevisiaegenome includes about 6,000 genes, which produce proteins with similar functions to that of more complex cells-including those in multicellular organisms like humans.
 
Approximately 5,000 of the 6,000 genes in the S. cerevisiae genome have been found to be "nonessential" - that is, the yeast can survive even when these genes are mutated so as to be nonfunctional (researchers determined this by observing the gene's expression when they were turned off individually). Even though the majority of the yeast's genes are nonessential, they may impart selective advantages that allow them to persist.  In putting together the synIII chromosome, the researchers sought to identify which of these individually nonessential genes could be safely deleted after accounting for multiple gene interactions.
 
Jef D. Boeke, Ph.D., and his team at Johns Hopkins University (JHU) in Baltimore, used a computer to rearrange and delete extra DNA segments that did not code for proteins.  They drew a rough sketch of what their desired synthetic chromosome might look like after altering stretches of the native chromosome, causing the genes to "scramble" when treated with a hormone called estradiol.  This allowed the team to control the evolution and size reduction of the S. cerevisiae genome.
 
With the simulated synIII model as a reference, undergraduate students enrolled in the "Build-A-Genome" course at JHU used DNA 'building blocks' to piece together larger strings of DNA (called 'minichunks'). Other sequences of artificial DNA were used to track the nonessential genes as they were added to the synthetic chromosome.  After 11 rounds of inserting new genes into the host yeast cell, the smaller, streamlined synIII sequence was all that remained.
 
Despite a few slight differences between the predicted sequence and the resulting synIII, yeast colonies implanted with the artificial chromosome grew as rapidly and were as genetically stable as the unmodified S. cerevisiae colonies; they were essentially indistinguishable.
 
Though a major objective of the study was to create a catalog of possible genes that could be deleted while still allowing the yeast to to survive under specific conditions, the research team faced challenges when they scrambled the individually nonessential genes. The team will need to make some modifications to gain greater control over rearrangement, but the fact that genome biologists can now design and construct human-made eukaryotic chromosomes is an important step in designer genome science.
 
Dr. Boeke and his team have demonstrated the feasibility of overhauling the yeast genome without affecting its ability to survive and reproduce. As they proceed in synthesizing the 15 remaining yeast chromosomes we will see how in the future we might reengineer genomes in more complex organisms.  Aside from this technology's clear applications in industry-S. cerevisiae can be used to produce biofuels-one day we might design and implant synthetic human chromosomes as gene therapies, or perhaps even replace complete genome sets to mend disease-causing mutations.


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Gene Therapy Boosts Cochlear Implants and Could Restore Hearing to the Deaf

Gene Therapy Boosts Cochlear Implants and Could Restore Hearing to the Deaf | Amazing Science | Scoop.it
Today researchers announced that they've been able to restore tonal hearing in guinea pigs with the new method of gene delivery.


The team implanted “bionic ears” in deaf guinea pigs, whose auditory systems are very similar to humans’. With the device, then, they delivered DNA that coded for a protein called brain-derived neruotrophic factor (BDNF), which encourages nerves to grow. The DNA was taken up by cells in the cochlea and, after two weeks, the nerves had grown significantly toward the electrodes. When the guinea pigs’ hearing was tested they found that animals that were once completely deaf had their hearing restored to almost normal levels.


It’s unclear, however, whether the treatment will work long-term: neuron production in the guinea pigs dropped off six weeks after the gene therapy. Researchers are also unsure whether tones heard after this treatment accurately reflect how they sound with normal hearing.


The technique is very close to being ready for human trials, where some of these questions should be answered. If it proves successful in clinical trials, the technique of combining gene therapy with device could also be used for other implants like retinal prosthesis and deep brain stimulation.

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Artificial blood 'will be manufactured in factories', paving the way for mass production of blood

Artificial blood 'will be manufactured in factories', paving the way for mass production of blood | Amazing Science | Scoop.it

Wellcome Trust-funded stem cell research has produced red blood cells fit for transfusion into humans, paving the way for the mass production of blood.


It is the stuff of gothic science fiction: men in white coats in factories of blood and bones. But the production of blood on an industrial scale could become a reality once a trial is conducted in which artificial blood made from human stem cells is tested in patients for the first time.


It is the latest breakthrough in scientists’ efforts to re-engineer the body, which have already resulted in the likes of 3d-printed bones and bionic limbs. Marc Turner, the principal researcher in the £5 million program funded by the Wellcome Trust, told The Telegraph that his team had made red blood cells fit for clinical transfusion.

Prof Turner has devised a technique to culture red blood cells from induced pluripotent stem (iPS) cells – cells that have been taken from humans and ‘rewound’ into stem cells. Biochemical conditions similar to those in the human body are then recreated to induce the iPS cells to mature into red blood cells – of the rare universal blood type O-.


“Although similar research has been conducted elsewhere, this is the first time anybody has manufactured blood to the appropriate quality and safety standards for transfusion into a human being,” said Prof Turner. There are plans in place for the trial to be concluded by late 2016 or early 2017, he said. It will most likely involve the treatment of three patients with Thalassaemia, a blood disorder requiring regular transfusions. The behavior of the manufactured blood cells will then be monitored.


“The cells will be safe,” he said, adding that there are processes whereby cells can be removed. The technique highlights the prospect of a limitless supply of manufactured type O- blood, free of disease and compatible with all patients.


“Although blood banks are well-stocked in the UK and transfusion has been largely safe since the Hepatitis B and HIV infections of the 1970s and 1980s, many parts of the world still have problems with transfusing blood,” said Prof Turner.

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DNA cube programmed to unzip and release trapped load in response to a carefully chosen trigger

DNA cube programmed to unzip and release trapped load in response to a carefully chosen trigger | Amazing Science | Scoop.it

Scientists in Canada have made DNA cubes that are programmed to unzip and reveal molecules locked inside them in response to a carefully chosen trigger. Hanadi Sleiman and colleagues at McGill University and the Jewish General Hospital in Montreal, designed the cubes to release the drug cargo they might be carrying only in diseased cells and not normal cells.


‘In the future, we would like to use our DNA cubes in the treatment of cancer and other diseases with a genetic component,’ says Sleiman. The cube opens into a flat assembly when a specific RNA sequence, in this case a gene product that is unique to prostate cancer cells, binds to two single-stranded DNA overhangs on the corners of the cube, disrupting the hydrogen-bonds that maintain the cube’s shape. Sleiman says it would be easy to change the sequence to which the cube responds and since the cube has two overhangs, ‘it would also be possible to make a cube that responds to two different triggers.’


The DNA cube was also modified with hydrophobic and hydrophilic chains to modulate its cellular uptake and prevent enzymatic degradation.


‘Compared with previous DNA origami-based designs the present system does not rely on the use of M13 [bacteriophage] DNA and can therefore be applied to many targets,’ comments Hiroshi Sugiyama, a DNA nanotechnology expert at Kyoto University in Japan.


Reference: K E Bujold et alChem. Sci., 2014, DOI: 10.1039/c4sc00646a

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Whooping cough bounces back and replacement vaccine seems weak at protecting kids

Whooping cough bounces back and replacement vaccine seems weak at protecting kids | Amazing Science | Scoop.it
A new type of pertussis vaccine introduced in the late 1990s may have led to the return of a disease that was nearly eradicated 40 years ago. Public opposition to vaccination hasn’t helped matters.


Whooping cough has turned up in North America after decades of near absence, and we have only ourselves to blame. In the last several years, the highly contagious microbe that causes whooping cough has spawned a string of outbreaks, adeptly piercing the shield of vaccination that once afforded solid protection against it. The last time whooping cough was this pervasive in the United States, Dwight Eisenhower was president and newscasters were smoking cigarettes on TV.


Caused by the Bordetella pertussis bacterium, whooping cough is emerging from the shadows in response to a fateful switch of vaccines embraced in the 1990s, just when it seemed the disease was licked. The vaccine used today has proved less potent than its predecessor. Meanwhile, curious changes are appearing in the pertussis bacterium itself, possibly in response to the weaker vaccine, and they may further undermine its effect. To top it off, a phobia against vaccines has induced some parents to skip or delay their kids’ shots, contributing to the disease’s spread.


“The newer vaccine’s protection wanes over time, the pathogen is morphing and more patients aren’t getting vaccinated on time,” says Jason Glanz, an epidemiologist at the University of Colorado Denver and the Kaiser Permanente Institute for Health Research Colorado. “Put them together and you get greatly increased risk.”

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It's a computer inside a cockroach: DNA nanobots deliver drugs in living animals based on calculations

It's a computer inside a cockroach: DNA nanobots deliver drugs in living animals based on calculations | Amazing Science | Scoop.it

A swarm of nanobots made of DNA can store molecules in their folds and deliver them to specific cells by performing complex calculations.


Nano-sized entities made of DNA that are able to perform the same kind of logic operations as a silicon-based computer have been introduced into a living animal. The DNA computers – known as origami robots because they work by folding and unfolding strands of DNA – travel around the insect's body and interact with each other, as well as the insect's cells. When they uncurl, they can dispense drugs carried in their folds.


"DNA nanorobots could potentially carry out complex programs that could one day be used to diagnose or treat diseases with unprecedented sophistication," says Daniel Levner, a bioengineer at the Wyss Institute at Harvard University.


Levner and his colleagues at Bar Ilan University in Ramat-Gan, Israel, made the nanobots by exploiting the binding properties of DNA. When it meets a certain kind of protein, DNA unravels into two complementary strands. By creating particular sequences, the strands can be made to unravel on contact with specific molecules – say, those on a diseased cell. When the molecule unravels, out drops the package wrapped inside. The team has now injected various kinds of nanobots into cockroaches. Because the nanobots are labelled with fluorescent markers, the researchers can follow them and analyse how different robot combinations affect where substances are delivered. The team says the accuracy of delivery and control of the nanobots is equivalent to a computer system.


"This is the first time that biological therapy has been able to match how a computer processor works," says co-author Ido Bachelet of the Institute of Nanotechnology and Advanced Materials at Bar Ilan University. "Unlike electronic devices, which are suitable for our watches, our cars or phones, we can use these robots in life domains, like a living cockroach," says Ángel Goñi Moreno of the National Center for Biotechnology in Madrid, Spain. "This opens the door for environmental or health applications."


DNA has already been used for storing large amounts of information and circuits for amplifying chemical signals, but these applications are rudimentary compared with the potential benefits of the origami robots.

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A mollusk's unique bioceramic nanostructure may lead to see-through body armor

A mollusk's unique bioceramic nanostructure may lead to see-through body armor | Amazing Science | Scoop.it
MIT researchers uncover the secrets behind a marine creature's defensive armor—one that is exceptionally tough, yet optically clear.


The shells of a sea creature, the mollusk Placuna placenta, are not only exceptionally tough, but also clear enough to read through. Now, researchers at MIT have analyzed these shells to determine exactly why they are so resistant to penetration and damage—even though they are 99 percent calcite, a weak, brittle mineral.


The shells' unique properties emerge from a specialized nanostructure that allows optical clarity, as well as efficient energy dissipation and the ability to localize deformation, the researchers found. The results are published this week in the journal Nature Materials, in a paper co-authored by MIT graduate student Ling Li and professor Christine Ortiz.


Ortiz, the Morris Cohen Professor of Materials Science and Engineering (and MIT's dean for graduate education), has long analyzed the complex structures and properties of biological materials as possible models for new, even better synthetic analogs.


Engineered ceramic-based armor, while designed to resist penetration, often lacks the ability to withstand multiple blows, due to large-scale deformation and fracture that can compromise its structural integrity, Ortiz says. In transparent armor systems, such deformation can also obscure visibility.


Creatures that have evolved natural exoskeletons—many of them ceramic-based—have developed ingenious designs that can withstand multiple penetrating attacks from predators. The shells of a few species, such as Placuna placenta, are also optically clear.

To test exactly how the shells—which combine calcite with about 1 percent organic material—respond to penetration, the researchers subjected samples to indentation tests, using a sharp diamond tip in an experimental setup that could measure loads precisely. They then used high-resolution analysis methods, such as electron microscopy and diffraction, to examine the resulting damage.

The material initially isolates damage through an atomic-level process called "twinning" within the individual ceramic building blocks: Part of the crystal shifts its position in a predictable way, leaving two regions with the same orientation as before, but with one portion shifted relative to the other. This twinning process occurs all around the stressed region, helping to form a kind of boundary that keeps the damage from spreading outward.

The MIT researchers found that twinning then activates "a series of additional energy-dissipation mechanisms … which preserve the mechanical and optical integrity of the surrounding material," Li says. This produces a material that is 10 times more efficient in dissipating energy than the pure mineral, Li adds.

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Construction of a Full Vertebrate Embryo from Two Opposing Morphogen Gradients

Construction of a Full Vertebrate Embryo from Two Opposing Morphogen Gradients | Amazing Science | Scoop.it

Scientists at the University of Virginia School of Medicine have overcome one of the greatest challenges in biology and taken a major step toward being able to grow whole organs and tissues from stem cells. By manipulating the appropriate signaling, the UVA researchers have turned embryonic stem cells into a fish embryo, essentially controlling embryonic development.

The research will have dramatic impact on the future use of stem cells to better the human condition, providing a framework for future studies in the field of regenerative medicine aimed at constructing tissues and organs from populations of cultured pluripotent cells.


In accomplishing this, U.Va. scientists Bernard and Chris Thisse have overcome the most massive of biological barriers. "We have generated an animal by just instructing embryonic cells the right way," said Chris Thisse of the School of Medicine's Department of Cell Biology.


The importance of that is profound. "If we know how to instruct embryonic cells," she said, "we can pretty much do what we want." For example, scientists will be able one day to instruct stem cells to grow into organs needed for transplant.


The researchers were able to identify the signals sufficient for starting the cascade of molecular and cellular processes that lead to a fully developed fish embryo. With this study came an answer to the longstanding question of how few signals can initiate the processes of development: amazingly, only two.


The study has shed light on the important roles these two signals play for the formation of organs and full development of a zebrafish embryo. Moreover, the Thisses are now able to direct embryonic development and formation of tissues and organs by controlling signal locations and concentrations.


The embryo they generated was smaller than a normal embryo, because they instructed a small pool of embryonic stem cells, but "otherwise he has everything" in terms of appropriate development, said Bernard Thisse of the Department of Cell Biology.

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CRISPR-CAS9 Reverses Disease Symptoms in Living Animals for First Time

CRISPR-CAS9 Reverses Disease Symptoms in Living Animals for First Time | Amazing Science | Scoop.it

MIT scientists report the use of a CRISPR methodology to cure mice of a rare liver disorder caused by a single genetic mutation. They say their study (“Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype”), published in Nature Biotechnology, offers the first evidence that this gene-editing technique can reverse disease symptoms in living animals. CRISPR, which provides a way to snip out mutated DNA and replace it with the correct sequence, holds potential for treating many genetic disorders, according to the research team.


“What's exciting about this approach is that we can actually correct a defective gene in a living adult animal,” says Daniel Anderson, Ph.D., the Samuel A. Goldblith associate professor of chemical engineering at MIT, a member of the Koch Institute for Integrative Cancer Research, and the senior author of the paper.


The recently developed CRISPR system relies on cellular machinery that bacteria use to defend themselves from viral infection. Researchers have copied this cellular system to create gene-editing complexes that include a DNA-cutting enzyme called Cas9 bound to a short RNA guide strand that is programmed to bind to a specific genome sequence, telling Cas9 where to make its cut.


At the same time, the researchers also deliver a DNA template strand. When the cell repairs the damage produced by Cas9, it copies from the template, introducing new genetic material into the genome. Scientists envision that this kind of genome editing could one day help treat diseases such as hemophilia, and others that are caused by single mutations.


For this study, the researchers designed three guide RNA strands that target different DNA sequences near the mutation that causes type I tyrosinemia, in a gene that codes for an enzyme called FAH. Patients with this disease, which affects about 1 in 100,000 people, cannot break down the amino acid tyrosine, which accumulates and can lead to liver failure. Current treatments include a low-protein diet and a drug called NTCB, which disrupts tyrosine production.


In experiments with adult mice carrying the mutated form of the FAH enzyme, the researchers delivered RNA guide strands along with the gene for Cas9 and a 199-nucleotide DNA template that includes the correct sequence of the mutated FAH gene.

“Delivery of components of the CRISPR-Cas9 system by hydrodynamic injection resulted in initial expression of the wild-type Fah protein in ~1/250 liver cells,” wrote the investigators. “Expansion of Fah-positive hepatocytes rescued the body weight loss phenotype.”


While the team used a high pressure injection to deliver the CRISPR components, Dr. Anderson envisions that better delivery approaches are possible. His lab is now working on methods that may be safer and more efficient, including targeted nanoparticles. 

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Holographic imaging for rapidly sorting stem cells and cancer cells

Holographic imaging for rapidly sorting stem cells and cancer cells | Amazing Science | Scoop.it

MIT scientists have developed a way to image cells (without fluorescent markers or other labels) as they flow through a tiny microfluidic channel for sorting. This is an important step toward cell-sorting systems that could help scientists separate stem cells at varying stages of development, or to distinguish healthy cells from cancerous cells, the scientists say.


Other cell-sorting methods require adding a fluorescent molecule that highlights the cells of interest, but those tags can damage the cells and make them unsuitable for therapeutic uses. The new method is based on a 2007 microscopy development that allowed the scientists to detail the interior of a living cell in three dimensions, without adding any fluorescent markers or other labels. This technique also revealed key properties, such as the cells’ density.


“Many stem cell applications require sorting of cells at different stages of differentiation. This can be done with fluorescent staining, but once you stain the cells they cannot be used,” says Yongjin Sung, a former postdoc in MIT’sLaser Biomedical Research Center and lead author of a paper describing the technique in the inaugural issue of the journal PRApplied.


“With our approach, you can utilize a vast amount of information about the 3-D distribution of the cells’ mass to sort them.” Instead of using fluorescent tags, the MIT method analyzes the cells’ index of refraction — a measurement of how much the speed of light is reduced as it passes through a material. Every material has a distinctive index of refraction, and this property can be used, along with cells’ volume, to calculate their mass and density.


Different parts of a cell, including individual organelles, have different indices of refraction, so the information generated by this approach can also be used to identify some of these internal cell structures, such as the nucleus and nucleolus, a structure located within the nucleus.


In the original 2007 version of this technology, known as tomographic phase microscopy, researchers led by the late MIT professor Michael Feld created 3-D images by combining a series of 2-D images taken as laser beams passed through cells from hundreds of different angles. This is the same concept behind CT scanning, which combines X-ray images taken from many different angles to create a 3-D rendering.


A key feature of the new MIT system is the use of a focused laser beam that can illuminate cells from many different angles, allowing the researchers to analyze the scattered light from the cells as they flow across the beam. Using a technique known as off-axis digital holography, the researchers can instantaneously record both the amplitude and phase of scattered light at each location of the cells. “As the cell flows across, we can effectively illuminate the entire sample from all angles without having to rotate a light source or the cell,” says former MIT graduate student Niyom Lue, a coauthor of the new paper.


The current system can image about 10 cells per second, but the researchers hope to speed it up to thousands of cells per second, which would make it useful for applications such as sorting stem cells. The researchers also hope to use the system to learn more about how cancer cells grow and respond to different drug treatments.

“This label-free method can look at different states of the cell, whether they are healthy or whether they maybe have cancer or viral or bacterial infections,” says Peter So, an MIT professor of mechanical engineering and biological engineering who is senior author of the new paper. “We can use this technique to look at the pathological state of the cell, or cells under treatment of some drug, and follow the population over a period of time.”


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Two-dimensional crystalline structure assembled from outer shells of a virus

Two-dimensional crystalline structure assembled from outer shells of a virus | Amazing Science | Scoop.it

From steel beams to plastic Lego bricks, building blocks come in many materials and all sizes. Today, science has opened the way to manufacturing at the nanoscale with biological materials. Potential applications range from medicine to optoelectronic devices.


In a paper published in Soft Matter, September 2013, scientists announced their discovery of a two-dimensional crystalline structure assembled from the outer shells of a virus. A virus consists of a protein shell protecting an interior consisting of either DNA or RNA.


"We are excited about the potential of virus-like particles as building blocks for creating new nanostructures," said the paper's lead author, Masafumi Fukuto, a physicist in the Condensed Matter Physics and Materials Science Department at Brookhaven National Laboratory. "For the particular virus that we studied, we discovered two new forms of 2D crystals that are distinct from previously observed hexagonal and square crystals."


The team used as their model system the turnip yellow mosaic virus (TYMV), which infects cruciferous vegetables like cabbages, cauliflower and broccoli. TYMV's protein shell resembles a soccer ball, which is characterized by a set of many axes with rotational symmetry, including two-fold axes between a pair of hexagons, three-fold axes through the center of hexagons, and five-fold axes through pentagons. This is known as icosahedral symmetry: all 20 hexagons are identical and all 12 pentagons are identical.


Fukuto described their work as new because it focuses on the structural diversity in the 2D arrays that arise from the constituent particle's high symmetry and regular shape. "Viruses have been used in previous studies of self-assembly, but in nearly all of those studies, the virus particles were treated as spheres and the ordered 2D arrays observed were hexagonal lattices," he said. "Second, this work is unique for demonstrating a rational approach to 2D crystallization that is based on controlling the interactions of virus particles, which occur at the surface of an aqueous solution where the 2D arrays are formed."

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Siberian scientists announce they now have a high chance to clone the woolly mammoth

Siberian scientists announce they now have a high chance to clone the woolly mammoth | Amazing Science | Scoop.it
Discovery of blood in creature frozen for 43,000 years is seen as major breakthrough by international team.


Viktoria Egorova, chief of the Research and Clinical Diagnostic Laboratory of the Medical Clinic of North-Eastern Federal University, said: 'We have dissected the soft tissues of the mammoth - and I must say that we didn't expect such results. The carcass that is more than 43,000 years old has preserved better than a body of a human buried for six months. 


'The tissue cut clearly shows blood vessels with strong walls. Inside the vessels there is haemolysed  blood, where for the first time we have found erythrocytes. Muscle and adipose tissues are well preserved. 

'We have also obtained very well visualised migrating cells of the lymphoid tissue, which is another great discovery. 


'The upper part of the carcass has been eaten by animals, yet the lower part with the legs and, astonishingly, the trunk are very well preserved. 


'We also have the mammoth's liver - very well preserved, too, and looks like with some solid fragments inside it. We haven't managed to study them yet, but the first suggestion is that possibly these are kidney stones. 


'Another discovery was intestines with remains of the vegetation the mammoth ate before its death, and a multi-chambered stomach what we've been working with today, collecting tissue samples. There is a lot more material that will have to go through laboratory research'. 

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