Amazing Science
721.6K views | +3 today
Amazing Science
Amazing science facts - 3D_printing • aging • AI • anthropology • art • astronomy • bigdata • bioinformatics • biology • biotech • chemistry • computers • cosmology • education • environment • evolution • future • genetics • genomics • geosciences • green_energy • history • language • map • material_science • math • med • medicine • microscopy • nanotech • neuroscience • paleontology • photography • photonics • physics • postings • robotics • science • technology • video
Your new post is loading...
Scooped by Dr. Stefan Gruenwald!

Engineers develop a new biosensor chip for detecting DNA mutations

Engineers develop a new biosensor chip for detecting DNA mutations | Amazing Science |

Bioengineers at the University of California, San Diego have developed an electrical graphene chip capable of detecting mutations in DNA. Researchers say the technology could one day be used in various medical applications such as blood-based tests for early cancer screening, monitoring disease biomarkers and real-time detection of viral and microbial sequences.  The advance was published June 13 in the online early edition of Proceedings of the National Academy of Sciences.


The chip essentially works by performing DNA strand displacement, the process in which a DNA double helix exchanges one strand for another complementary strand. The new complementary strand—which, in this case, contains the single nucleotide mutation—binds more strongly to one of the strands in the double helix and displaces the other strand. In this study, the DNA probe is a double helix containing two complementary DNA strands that are engineered to bind weakly to each other: a “normal” strand, which is attached to the graphene transistor, and a “weak” strand, in which four the G’s in the sequence were replaced with inosines to weaken its bond to the normal strand. DNA strands that have the perfectly matching complementary sequence to the normal strand—in other words, strands that contain the SNP—will bind to the normal strand and knock off the weak strand. Researchers engineered the chip to generate an electrical signal when an SNP-containing strand binds to the probe, allowing for quick and easy SNP detection in a DNA sample. 

No comment yet.
Scooped by Dr. Stefan Gruenwald!

Using CRISPR as a recording device inside living bacteria

Using CRISPR as a recording device inside living bacteria | Amazing Science |

A small team of researchers at Harvard University has taken another look at CRISPR and has found that it can be used as a recording device of sorts, keeping track of when and where a given bacterium has been exposed to different viruses. In their paper published in the journal Science, the team describes their study, their findings and the ways such natural recordings might be useful.


CRISPR has been in the news a lot of late, primarily due to its use in gene editing—but lost in all the news is the actual basis of the technology. Like humans, bacteria have a unique immune system, which is known as CRISPR/Cas, and it works by cutting out pieces of DNA (called oligomers) when attacking viruses and integrating those pieces into its own genome, which is later used to give the bacterium historical knowledge when fighting the virus should it appear again. The researchers with this new effort noted that the oligomers that are placed in the genome are done so sequentially, which means they form a record of viral attacks. To see its history, the team reasoned, the genome need only be sequenced.


To test this idea, the researchers used a simplified version of E. coli, which still contained Cas1 and Cas2, the enzymes needed for snipping and adding oligomers, but no other immune system functionality. They then directly exposed it to various DNA sequences over a period of time, allowed it to snip and add to its genome, then sequenced the bacterium to see if the theory held up. The team reports that it did indeed. Taking the idea further they found that by introducing modified versions of Cas 1 and Cas2 that they could actually create different recording modes.


The team suggests this new bit of knowledge regarding CRISPR might be used to aid in creating bacteria that could be used as sensors of a sort, offering recording evidence of a host of different microorganisms in a given environment. Such sensors could prove useful in applications ranging from soil testing, to human gut biome analysis to atmospheric probes.

No comment yet.
Scooped by Dr. Stefan Gruenwald!

Gene drives spread their wings

Gene drives spread their wings | Amazing Science |
Gene drives may wipe out malaria and take down invasive species. But they may be difficult to control.


enies are said to have the power to grant three wishes. But genies recently released from laboratory flasks promise to fulfill nearly any wish a biologist can dream up. End the scourge of insect-borne diseases? Check. Inoculate endangered amphibians against killer fungi? Yes. Pluck invasive species from environments where they don’t belong? As you wish.


These genies aren’t magical; they are research tools known as gene drives — clever bits of engineered DNA designed to propel themselves into the DNA of a pesky or troubled organism. A gene drive is a targeted contagion intended to spread within species, forever altering the offspring.


Gene drive enthusiasts say these genies could wipe out malaria, saving more than half a million lives each year. Invasive species, herbicide-resistant weeds and pesticide-resistant bugs could be driven out of existence. Animals that carry harmful viruses could be immunized with ease.


Scientists have sought the power of gene drives for decades. But only with the emergence of a genetic tool called CRISPR/Cas9 — the bottle opener that unleashed the genie — has gene drive technology offered the prospect of providing a speedy means to end some of the world’s greatest health and ecological scourges.


“Everything is possible with CRISPR,” says geneticist Hugo Bellen. “I’m not kidding.” But genes designed to spread through populations and alter ecosystems could have unforeseen consequences. Researchers have designed ways to keep gene drives confined in the lab, but no such safety nets exist for gene drives released into the wild. A technology to eradicate entire species, even when those species are pests, raises ethical and regulatory issues that scientific and government agencies are just beginning to consider.


No comment yet.
Scooped by Dr. Stefan Gruenwald!

Plan to build human genome from scratch could kick off in 2016

Plan to build human genome from scratch could kick off in 2016 | Amazing Science |

A group of 25 scientists officially announced their plan to build a human genome from scratch within the next 10 years. They have also given more details about their intended applications for the synthetic DNA – but not everyone is convinced by their approach.

The team bills this grand challenge as a natural extension of the Human Genome Project. If that was about reading – or sequencing – the code of life, this new project proposes to write it, chemically synthesising each letter or base pair.

Poring over our DNA has limitations, the team argues. “Reading the genome can only get you so far,” says Susan Rosser, a co-author on the paper and the director of the Mammalian Synthetic Biology Research Centre at the University of Edinburgh, UK. “At some point you have to build it.”

The team, which is led by maverick geneticist George Church at Harvard University and Andrew Hessel of design software company Autodesk, says it is aiming to launch the ambitious initiative – known as The Human Genome Project–Write – this year, depending on raising an initial £100 million.

Stem cell boon
Within 10 years, the project’s primary goal is to engineer large genomes of up to 100-billion base pairs (a human genome is 3 billion base pairs), which could include “whole genome engineering of human cell lines and other organisms of agricultural and public health significance”. This will require technological development early on in the project “to propel large-scale genome design and engineering,” the researchers write.

While difficult to put a figure on at this early stage, the team says it expects the final bill for the project to be less than the $3-billion cost of the first Human Genome Project.

Alongside the main project, they outline several pilot projects that will take advantage of the progress as it is made. Those discussed in the paper published today include the development of an ultra-safe line of cells that would be virus resistant, cancer resistant and free of potentially harmful genes that could lead, for example, to prion diseases.

No comment yet.
Rescooped by Dr. Stefan Gruenwald from Limitless learning Universe!

Researchers develop technique allowing them to map important regulatory DNA regions

Researchers develop technique allowing them to map important regulatory DNA regions | Amazing Science |

For a long time dismissed as "junk DNA", we now know that also the regions between the genes fulfil vital functions. Mutations in those DNA regions can severely impair development in humans and may lead to serious diseases later in life. Until now, however, regulatory DNA regions have been hard to find. Scientists around Prof. Julien Gagneur, Professor for Computational Biology at the Technical University of Munich (TUM) and Prof. Patrick Cramer at the Max Planck Institute (MPI) for Biophysical Chemistry in Göttingen have now developed a method to find regulatory DNA regions which are active and controlling genes.


Björn Schwalb and Margaux Michel, members of Cramer’s team, as well as Benedikt Zacher, scientist in Gagneur’s group, have now succeeded in developing a highly sensitive method to catch and identify even very short-lived RNA molecules – the so-called TT-Seq (transient transcriptome sequencing) method. The results are reported in the latest issue of the renowned scientific journal Science on June 3rd. In order to catch the RNA molecules, the three junior researchers used a trick: They supplied cells with a molecule acting as a kind of anchor for a couple of minutes. The cells subsequently incorporated the anchor into each RNA they made during the course of the experiment. With the help of the anchor, the scientists were eventually able to fish the short-lived RNA molecules out of the cell and examine them.


"The RNA molecules we caught with the TT-Seq method provide a snapshot of all DNA regions that were active in the cell at a certain time – the genes as well as the regulatory regions between genes that were so hard to find until now," Cramer explains. "With TT-Seq we now have a suitable tool to learn more about how genes are controlled in different cell types and how gene regulatory programs work," Gagneur adds.


In many cases, researchers have a pretty good idea which genes play a role in a certain disease, but do not know which molecular switches are involved. The scientists around Cramer and Gagneur are hoping to be able to use the new method to uncover key mechanisms that play a role during the emergence or course of a disease. In a next step they want to apply their technique to blood cells to better understand the progress of a HIV infection in patients suffering from AIDS.

Via Integrated DNA Technologies, CineversityTV
No comment yet.
Scooped by Dr. Stefan Gruenwald!

Systemic RNA delivery to dendritic cells exploits antiviral defense for cancer immunotherapy

Systemic RNA delivery to dendritic cells exploits antiviral defense for cancer immunotherapy | Amazing Science |

Lymphoid organs, in which antigen presenting cells (APCs) are in close proximity to T cells, are the ideal microenvironment for efficient priming and amplification of T-cell responses. However, the systemic delivery of vaccine antigens into dendritic cells (DCs) is hampered by various technical challenges. Here we show that DCs can be targeted precisely and effectively in vivo using intravenously administered RNA-lipoplexes (RNA-LPX) based on well-known lipid carriers by optimally adjusting net charge, without the need for functionalization of particles with molecular ligands. The LPX protects RNA from extracellular ribonucleases and mediates its efficient uptake and expression of the encoded antigen by DC populations and macrophages in various lymphoid compartments. RNA-LPX triggers interferon-α (IFNα) release by plasmacytoid DCs and macrophages.


Consequently, DC maturation in situ and inflammatory immune mechanisms reminiscent of those in the early systemic phase of viral infection are activated. We show that RNA-LPX encoding viral or mutant neo-antigens or endogenous self-antigens induce strong effector and memory T-cell responses, and mediate potent IFNα-dependent rejection of progressive tumous. A phase I dose-escalation trial testing RNA-LPX that encode shared tumor antigens is ongoing. In the first three melanoma patients treated at a low-dose level, IFNα and strong antigen-specific T-cell responses were induced, supporting the identified mode of action and potency. As any polypeptide-based antigen can be encoded as RNA, RNA-LPX represent a universally applicable vaccine class for systemic DC targeting and synchronized induction of both highly potent adaptive as well as type-I-IFN-mediated innate immune mechanisms for cancer immunotherapy.

No comment yet.
Scooped by Dr. Stefan Gruenwald!

Scientists Find a Better Way to Make Structures to Create DNA Based Tech

Scientists Find a Better Way to Make Structures to Create DNA Based Tech | Amazing Science |
Researchers have designed a new algorithm that automates the manipulation and sculpting of DNA into different shapes—a process known as DNA origami.


A team of researchers from MIT, Arizona State University, and Baylor University have devised a new computer algorithm that does all the hard work for you. The results of their research have been published in the journal Science.


“The paper turns the problem around from one in which an expert designs the DNA needed to synthesize the object, to one in which the object itself is the starting point, with the DNA sequences that are needed automatically defined by the algorithm,” says Mark Bathe, associate professor of biological engineering at MIT, and lead researcher for the study.


The new algorithm, which the team has called DAEDALUS, automates the entire business of sculpting DNA shapes; essentially, you begin with the desired shape (which must have a closed surface) and feed it into the algorithm, which then maps out the order of bases (adenine, guanine, cytosine and thymine) needed to produce the DNA “scaffold.”


DAEDALUS means “open source” DNA origami, enabling anyone with the inclination and access to the algorithm to design and create their own DNA-based, nanoscale objects. What Henry Ford’s assembly line concept did for manufacturing, DAEDALUS promises to do for nanoscale structures.

No comment yet.
Scooped by Dr. Stefan Gruenwald!

Gene editing creates hornless cattle

Gene editing creates hornless cattle | Amazing Science |
Alison L. Van Eenennaam, PhD, a geneticist and cooperative extension specialist also at UC-Davis, is working with the Minnesota-based company Recombinetics on, among other things, a project that has produced some of the Holstein dairy cattle that lack horns by editing one allele to match another found in Angus cattle.

“We’ve still got a dairy cow with all the good dairy genetics,” she said. “We’ve just gone in and tweaked a little snippet of DNA at the gene that makes horns and made it so it’s the variant for Angus, which doesn’t grow horns.”
No comment yet.
Rescooped by Dr. Stefan Gruenwald from Fragments of Science!

Study captures ultrafast motion of proteins

Study captures ultrafast motion of proteins | Amazing Science |

A new study by an international team of researchers, affiliated with Ulsan National Institute of Science and Technology (UNIST) has announced that they have succeeded for the first time in observing the structural change.


The breakthrough comes from a research, conducted by Professor Chae Un Kim (School of Natural Science) of UNIST in collaboration with researchers from Soongsil University, Cornell University, and University of Florida. Carbonic anhydrase, which is found within red blood cells, is a crucial enzyme that stabilizes carbon dioxide (CO2 ) concentrations. This enzyme catalyzes a reaction converting CO2 and water into carbonic acid, which associates into protons and bicarbonate ions.


Moreover, it is also known that carbonic anhydraseis is able to catalyze at a rate of 106 reactions per second. In the absence of this catalyst, the conversion from CO2 to bicarbonate, and vice versa, would be extremely slow and difficult.


One of the important functions of the enzyme in humans is to adjust the acidity of the chemical environment to prevent damage to the body, as well as to help transport carbon dioxide out from tissue cells to the lungs. Although carbonic anhydrase performs a lot of beneficial functions, defects in the enzyme are responsible for developing diseases, such as glaucoma, acidemia, or osteopetrosis.


Prof. Kim, the lead researcher of the study states, "The reaction rate of carbonic anhydrase is one of the fastest of all enzymes." He continues, "Due to the rapid movement of proteins, direct observation for such movement has been extremely difficult to obtain, protein scientists say."


In this study, Prof. Kim's team used their own method of "High-pressure Crycooling" and "X-ray Crystallography" to capture the gaseous carbon dioxide in crystals of carbonic anhydrase and follow the sequential structure changes as the carbon dioxide is released. The results of the study will not only greatly contribute to the future biomedical research and new drug development, but will also help make carbon capture more economic.


According to Prof. Kim of UNIST, "This study also shows technical methods that may be applicable to other enzymes that bind and react to low-molecular weight substrates, such as CO2 and NO2 ."

Via Mariaschnee
No comment yet.
Rescooped by Dr. Stefan Gruenwald from Erba Volant - Applied Plant Science!

The race to create super-crops

The race to create super-crops | Amazing Science |
Old-fashioned breeding techniques are bearing more fruit than genetic engineering in developing hyper-efficient plants.


Big corporations such as DuPont Pioneer in Johnston, Iowa, have spent more than a decadedeveloping improved crops through genetic engineering, and some companies say that their transgenic varieties look promising in field trials. But there are still no fertilizer-frugal transgenic crops on the market, and several agricultural organizations around the globe are reviewing their biotechnology initiatives in this area.


Plant biologist Allen Good of the University of Alberta in Edmonton, Canada, spent years working with companies to develop genetically modified (GM) crops that require little fertilizer, but he says that this approach has not been as fruitful as conventional techniques. The problem is that there are so many genes involved in nutrient uptake and use — and environmental variations alter how they are expressed.


“Nutrient efficiency was supposed to be one of those traits with broad applicability that could make companies lots of money. But they haven't developed the way we thought,” says Good.


Despite the scientific and breeding challenges, some researchers say that all strategies must be explored to develop crops that are less nutrient needy. With the global population heading towards 10 billion people by 2050, frugal crops could be essential to feed the planet. “There is a huge worldwide potential for these traits to help increase food production and sustainable development,” says Matin Qaim, an agricultural economist at the University of Göttingen in Germany.

Via Meristemi
No comment yet.
Rescooped by Dr. Stefan Gruenwald from Cancer Immunotherapy Review!

Duke's Poliovirus Oncolytic Therapy Wins "Breakthrough" Status

Duke's Poliovirus Oncolytic Therapy Wins "Breakthrough" Status | Amazing Science |

The recombinant poliovirus therapy developed at the Preston Robert Tisch Brain Tumor Center at Duke Health has been granted “breakthrough therapy designation” from the U.S. Food and Drug Administration.


Duke’s poliovirus therapy is an immunotherapy developed in the laboratory of Matthias Gromeier, M.D., a professor in the departments of Neurosurgery, Molecular Genetics and Microbiology, and Medicine at Duke University School of Medicine. 


Using a modified form of poliovirus that has been altered to eliminate harm, the therapy preferentially attacks cancer cells, which have an abundance of receptors that work like magnets to attract the poliovirus. The modified poliovirus then kills the infected tumor cells while also igniting an additional immune response.


A phase I clinical trial using the therapy was launched in 2012 to determine an optimal dose of the novel treatment among adult patients with glioblastoma whose cancer had returned after receiving traditional therapy.


Early testing found that lower doses of the treatment were superior to higher doses. Of 23 glioblastoma patients enrolled at the optimal dose level, 15 are still alive and enrollment is ongoing. Three patients treated early using different dosages are still alive more than 36 months after treatment. With current standard therapy, the median survival time for people with glioblastoma is 14.6 months. 


The Duke team is moving to expand its work and open a clinical trial for children with brain tumors, which is expected to begin enrollment before year’s end. The researchers have also received federal grants to explore the therapy’s effect on solid tumors. Laboratory studies are already underway in breast cancer models.

Via Krishan Maggon
No comment yet.
Scooped by Dr. Stefan Gruenwald!

Scientists digitally mimic evolution to create novel proteins from components

Scientists digitally mimic evolution to create novel proteins from components | Amazing Science |

Here’s an innovative idea: create new proteins by simply “sewing” together pieces of existing proteins. That’s exactly what researchers at the University of North Carolina School of Medicine have done to design new “cellular machines” needed to understand and battle diseases. Published today in the journal Science, the new technique, called SEWING, was inspired by natural evolutionary mechanisms that also recombine portions of the 100,000 different known proteins in the body.


Traditionally, researchers have used computational protein design to recreate in the laboratory what already exists in the natural world. But in recent years, their focus has shifted toward inventing novel proteins with new functionality. Those design projects all start with a specific structural “blueprint” in mind, and as a result are limited.


Senior study author Brian Kuhlman, PhD, professor of biochemistry and biophysics, and his colleagues believe that by removing the limitations of a pre-determined blueprint and taking cues from evolution, they can more easily create new functional proteins. “We can now begin to think about engineering proteins to do things that nothing else is capable of doing,” he said. “The structure of a protein determines its function, so if we are going to learn how to design new functions, we have to learn how to design new structures. Our study is a critical step in that direction and provides tools for creating proteins that haven’t been seen before in nature.”


To mimic the mechanisms of natural protein evolution, they developed a computer design strategy called SEWING (Structure Extension With Native-substructure Graphs):


  1. The researchers digitally chopped up naturally occurring proteins into well-defined pieces.
  2. They performed a series of computational tests to figure out which pieces would fit well together. In nature, this step would involve looking for stretches of amino acid sequences that are similar between proteins. On the computer, it involved searching for regions of structural similarity to make things fit in the right place.
  3. They whittled down the list to the top 21 proteins, which they produced in the lab.
  4. To confirm what they created, they took pictures of these proteins using x-ray crystallography and nuclear magnetic resonance (NMR), and found that the proteins contained all the unique structural varieties they had designed on the computer.

Currently, the researchers are using SEWING to create proteins that can bind to several other proteins at a time. Many of the most important natural proteins are similar multitaskers, including the blood protein hemoglobin, which carries four copies of oxygen from the lungs to the body’s tissues.

No comment yet.
Scooped by Dr. Stefan Gruenwald!

Penn Bioengineers Show Why Lab-made Stem Cells Might Fail: Errors in DNA Folding

Penn Bioengineers Show Why Lab-made Stem Cells Might Fail: Errors in DNA Folding | Amazing Science |

Induced pluripotent stem cells hold promise for regenerative medicine because they can, in theory, turn into any type of tissue and because they are made from a patient’s own adult cells, guaranteeing compatibility. However, the technique that turns adult cells into these iPS cells is not foolproof; after reverting to their pluripotent state, these cells don’t always correctly differentiate back into adult cells. 


Researchers from the University of Pennsylvania have now discovered one of the reasons why: the reversion process does not always fully capture the way a cell’s genome is folded up inside its nucleus. This folding configuration directly influences gene expression and therefore the functionality of the cell.


The new study shows that current techniques might not produce iPS cells that are equivalent to the pluripotent stem cells found in embryos, as some clones retain folding patterns that partially resemble those found in the adult cells from which they are made.  


Led by Jennifer Phillips-Cremins, assistant professor in the School of Engineering and Applied Science’s Department of Bioengineering, and Jonathan Beagan, a graduate student in her lab, the study, published in the journal Cell Stem Cell, also suggests ways of minimizing these folding errors.


Though techniques for reverting adult cells into iPS cells have existed for a decade and avoid the issues surrounding the use of embryonic stem cells that have stymied research into regenerative medicine, clinical investigations of these cells have been cautious and slow. IPS cells can fail to correctly differentiate into the desired tissue. Moreover, there are also concerns that the resulting tissue could have unforeseen genetic abnormalities or could become cancerous.


Even outside the clinical applications, many researchers are interested in iPS cells as a way of generating a “disease in a dish.” Rather than taking a tissue sample from a patient with a genetic disorder, which is especially challenging when the affected organ is the brain, researchers could use iPS cells derived from that patient’s skin cells to grow model organs as needed. Observing the development of those tissues could provide clues to the progression of the disease, as well as serve as ideal test-beds for treatments not yet approved for use in humans.


In both clinical and research applications, however, the traits that allow for the generation of “high quality” iPS cells capable of correctly differentiating into the desired tissue with no genetic abnormalities is unclear. “We know there is a link between the topology of the genome and gene expression,” Phillips-Cremins said, “so this motivated us to explore how the genetic material is reconfigured in three dimensions inside the nucleus during the reprogramming of mature brain cells to pluripotency. We found evidence for sophisticated configurations that differ in important ways between iPS cells and embryonic stem cells.”

No comment yet.
Scooped by Dr. Stefan Gruenwald!

Gene circuits in live cells can perform complex computations

Gene circuits in live cells can perform complex computations | Amazing Science |
MIT researchers have developed a technique to integrate both analogue and digital computation in living cells, allowing them to form gene circuits capable of carrying out complex processing operations.


Living cells are capable of performing complex computations on the environmental signals they encounter. These computations can be continuous, or analogue, in nature — the way eyes adjust to gradual changes in the light levels. They can also be digital, involving simple on or off processes, such as a cell’s initiation of its own death. Synthetic biological systems, in contrast, have tended to focus on either analogue or digital processing, limiting the range of applications for which they can be used.


But now a team of researchers at MIT has developed a technique to integrate both analogue and digital computation in living cells, allowing them to form gene circuits capable of carrying out complex processing operations. The synthetic circuits, presented in a paper published today in the journal Nature Communications, are capable of measuring the level of an analogue input, such as a particular chemical relevant to a disease, and deciding whether the level is in the right range to turn on an output, such as a drug that treats the disease. In this way they act like electronic devices known as comparators, which take analogue input signals and convert them into a digital output, according to Timothy Lu, an associate professor of electrical engineering and computer science and of biological engineering, and head of the Synthetic Biology Group at MIT’s Research Laboratory of Electronics, who led the research alongside former microbiology PhD student Jacob Rubens. “Most of the work in synthetic biology has focused on the digital approach, because digital systems are much easier to program,” Lu says.


However, since digital systems are based on a simple binary output such as 0 or 1, performing complex computational operations requires the use of a large number of parts, which is difficult to achieve in synthetic biological systems.


“Digital is basically a way of computing in which you get intelligence out of very simple parts, because each part only does a very simple thing, but when you put them all together you get something that is very smart,” Lu says. “But that requires you to be able to put many of these parts together, and the challenge in biology, at least currently, is that you can’t assemble billions of transistors like you can on a piece of silicon,” he says.


The mixed signal device the researchers have developed is based on multiple elements. A threshold module consists of a sensor that detects analogue levels of a particular chemical.

This threshold module controls the expression of the second component, a recombinase gene, which can in turn switch on or off a segment of DNA by inverting it, thereby converting it into a digital output.


If the concentration of the chemical reaches a certain level, the threshold module expresses the recombinase gene, causing it to flip the DNA segment. This DNA segment itself contains a gene or gene-regulatory element that then alters the expression of a desired output.


“So this is how we take an analogue input, such as a concentration of a chemical, and convert it into a 0 or 1 signal,” Lu says. “And once that is done, and you have a piece of DNA that can be flipped upside down, then you can put together any of those pieces of DNA to perform digital computing,” he says.


The team has already built an analogue-to-digital converter circuit that implements ternary logic, a device that will only switch on in response to either a high or low concentration range of an input, and which is capable of producing two different outputs.

Ziggi Ivan Santini, PhD.'s curator insight, June 13, 3:35 AM

Researchers have developed a technique to integrate both analogue and digital computation in living cells, allowing them to form gene circuits capable of carrying out complex processing operations.

Scooped by Dr. Stefan Gruenwald!

Study: Molecular motors shape chromosome structure

Study: Molecular motors shape chromosome structure | Amazing Science |

Human cells contain 23 pairs of chromosomes that form a loosely organized cluster in the cell nucleus. When cells divide, they must first condense these chromosomes — each of which when fully extended is a thousand times longer than the cell’s nucleus and physically indistinguishable from the others — into compact structures that can be easily separated and packaged into their offspring.


An MIT-led team has now developed a model that explains how cells handle this difficult task. In computer simulations, the researchers demonstrate that certain molecular “machines” can transform chromosomes from a loosely tangled rope into a series of tiny loops that condense each chromosome and allow it to extricate itself from the others. Moreover, the researchers demonstrate that a similar model explains how chromosomes are organized when cells are not dividing, and they hypothesize that loop extrusion by molecular motors splits chromosomes into separate domains, helping to control which genes are expressed in a given cell.


This mechanism, outlined in three recent papers published in Cell Reports, eLife, and Biophysical Journal, suggests that chromosome organization relies on proteins that act as molecular motors that pull strands of DNA into progressively larger loops. The MIT team suggests that two proteins thought to function primarily as “staples” that hold DNA together, cohesin and condensin, can also actively manipulate DNA.


“Nobody has ever directly observed this mechanism of loop extrusion. If it exists, it will solve lots of problems,” says Leonid Mirny, a professor of physics in MIT’s Institute for Medical Engineering and Sciences, who led the research. “We will know how chromosomes condense, how they segregate, how genes talk to enhancers. Lots of things can be solved by this mechanism.”

No comment yet.
Rescooped by Dr. Stefan Gruenwald from DNA and RNA Research!

DNA typo tracker uncovers glitches in gene regulation

DNA typo tracker uncovers glitches in gene regulation | Amazing Science |

A new tool allows researchers to identify thousands of genome errors in dozens of people at once.


A new tool allows researchers to identify thousands of genome errors in dozens of people at once, a huge boost in efficiency from previous methods1. The technique is a variation on so-called ChIP-Seq, which detects segments of DNA that serve as landing strips for proteins that control gene expression. It allows researchers to home in on three times as many of these landing strips as they previously could, and in a fraction of the time. It also pinpoints variants that deter regulatory proteins from touching down on the DNA, and that may be associated with conditions such as autism.

Large genomic studies have identified many of these variants, but offer few clues to their function. The new work uncovers interactions between genetic sequences and regulatory proteins, hinting at the variants’ roles in gene expression. The work appeared in April in Cell.


Scientists perform ChIP-Seq by growing cells in a tube, breaking them open to release DNA and then using antibodies as ‘molecular magnets’ to pull out stretches of the genome bound to proteins. They then sequence those regions to see how they differ between individuals with and without a condition such as autism. But scientists had to perform these analyses on one genome at a time, and normal variations between individuals can mask genetic variants associated with a condition. The assays are also expensive and time-consuming, limiting the number of samples that researchers can analyze.


The new method sidesteps these limitations by pooling genetic samples from a group of people and performing ChIP-Seq on the pooled DNA. If an individual in the group carries a mutation that disrupts a landing zone — preventing or impeding the protein’s binding — the mutated strip should be underrepresented in the extracted pool of molecules.


The researchers tested their technique on cell lines from 60 unrelated people, using antibodies to pull out five regulatory proteins that control immune cell development. They then counted the number of copies of each piece of DNA bound to each of those proteins.


Up to 3 percent of the extracted DNA-protein pieces was underrepresented in the pool of molecules. The researchers identified errors in the DNA segments that may prevent one or more regulatory proteins from binding. Comparing the binding sites with those identified in a previous ChIP-Seq study, the researchers found a near-perfect overlap, confirming the new method’s accuracy2.

Via Integrated DNA Technologies
No comment yet.
Rescooped by Dr. Stefan Gruenwald from DNA and RNA Research!

Scientists Find New Roles For small nucleolar RNAs (SNORDs)

Scientists Find New Roles For small nucleolar RNAs (SNORDs) | Amazing Science |

Small nucleolar RNAs play a role in the development of some diseases.


C/D box small nucleolar RNAs (SNORDs) are abundant, short, nucleoli-residing, noncoding RNAs that guide the methyltransferase fibrillarin to perform 2′-O-methylation of target RNAs. Scientists now identified 29 SNORDs present in a fibrillarin-containing fraction as well as a fibrillarin-free fraction enriched in spliceosomes. One of these SNORDs, SNORD27, directs rRNA methylation and regulates alternative pre-mRNA splicing (AS) of E2F7 pre-mRNA, a transcriptional repressor of cell cycle-regulated genes.SNORD27 likely regulates E2F7 pre-mRNA AS by masking splice sites through base pairing. This previously unidentified function of SNORDs increases the number of factors regulating AS, a critical step in the expression of the vast majority of human genes, and highlights a potential coupling between AS, cell cycle, proliferation, and ribosome biogenesis.

Via Integrated DNA Technologies
No comment yet.
Scooped by Dr. Stefan Gruenwald!

Engineered bacterium grows on carbon dioxide and hydrogen and excretes fuel alcohols

Engineered bacterium grows on carbon dioxide and hydrogen and excretes fuel alcohols | Amazing Science |

Harvard Chemist Daniel Nocera has announced during a lecture at the Energy Policy Institute in Chicago, that he and his colleagues have engineered a bacterium that has made it capable of taking in carbon dioxide and hydrogen, and excreting several types of alcohol fuels, along with biomass that can be burned and used as an energy source. During the talk, he claimed that a paper he and his colleagues have written regarding the work will soon be published in the journal Science.

No comment yet.
Scooped by Dr. Stefan Gruenwald!

Silk Stabilizes Blood Samples for Months at High Temperatures

Silk Stabilizes Blood Samples for Months at High Temperatures | Amazing Science |

Researchers at Tufts University have stabilized blood samples for long periods of time without refrigeration and at high temperatures by encapsulating them in air-dried silk protein.  The technique, which is published online this week in the Proceedings of the National Academy of Sciences, has broad applications for clinical care and research that rely on accurate analysis of blood and other biofluids.


Blood contains proteins, enzymes, lipids, metabolites, and peptides that serve as biomarkers for health screening, monitoring and diagnostics. Both research and clinical care often require blood to be collected outside a laboratory.  However, unless stored at controlled temperatures, these biomarkers rapidly deteriorate, jeopardizing the accuracy of subsequent laboratory analysis. Existing alternative collection and storage solutions, such as drying blood on paper cards, still fail to effectively protect biomarkers from heat and humidity.


The Tufts scientists successfully mixed a solution or a powder of purified silk fibroin protein extracted from silkworm cocoons with blood or plasma and air-dried the mixture. The air-dried silk films were stored at temperatures between 22 and 45 degrees C (71.6 to 113 degrees F).   At set intervals, encapsulated blood samples were recovered by dissolving the films in water and analyzed.


"This approach should facilitate outpatient blood collection for disease screening and monitoring, particularly for underserved populations, and also serve needs of researchers and clinicians without access to centralized testing facilities. For example, this could support large-scale epidemiological studies or remote pharmacological trials," said senior and corresponding author David L. Kaplan, Ph.D., Stern Family Professor in the Department of Biomedical Engineering at Tufts School of Engineering.  


 "We found that biomarkers could be successfully analyzed even after storage for 84 days at temperatures up to 113 degrees F. Encapsulation of samples in silk provided better protection than the traditional approach of drying on paper, especially at these elevated temperatures which a shipment might encounter during overseas or summer transport," said the paper’s co-first author Jonathan A. Kluge, who earned both his Ph.D. and B.S. from Tufts School of Engineering and was a postdoctoral associate in the Kaplan lab when the research was done.  


The paper noted that the silk-based technique requires accurate starting volumes of the blood or other specimens to be known, and salts or other buffers are needed to reconstitute samples for accurate testing of certain markers. 


Kaplan, whose specialty is biopolymer engineering, has studied the unique properties and applications of silk for more than 20 years. He and his collaborators have successfully demonstrated silk’s ability to stabilize a variety of bioactive materials including antibiotics, vaccines, enzymes and monoclonal antibiotics with numerous biomedical and biomaterial applications. He also holds Tufts faculty appointments in the Department of Chemical and Biological Engineering, School of Medicine, School of Dental Medicine and Department of Chemistry in the School of Arts and Sciences.

No comment yet.
Scooped by Dr. Stefan Gruenwald!

Mirror-image polymerase copies mirror-world DNA

Mirror-image polymerase copies mirror-world DNA | Amazing Science |

Researchers at Tsinghua University in Beijing have created a mirror-image version of a protein that performs two of the most fundamental processes of life: copying DNA and transcribing it into RNA.

The work is a “small step” along the way to making mirror-image life forms, says molecular biologist Jack Szostak of Harvard Medical School in Boston, Massachusetts. “It’s a terrific milestone,” adds his Harvard colleague George Church, who hopes one day to create an entire mirror-image cell.

Many organic molecules are ‘chiral’: that is, they can exist in mirror-image forms that cannot be superimposed, like a right-handed and left-handed glove. But life almost always employs one version: cells use left-handed amino acids, and have DNA that twists like a right-handed screw, for instance.


Life forms created in this mirrored way would not be able to use any of the biological material of our normal world.


In their research paper, the Tsinghua researchers also present their work as an effort to investigate why life’s chirality is the way it is. This remains mysterious: it may simply be down to chance, or it could have been triggered by a fundamental asymmetry in nature.


But Steven Benner, at the Foundation for Applied Molecular Evolution in Alachua, Florida, says it’s unlikely that creating a mirror form of biochemical life could shed any light on this question. Almost every physical process behaves identically when viewed in a mirror. The only known exceptions — called ‘parity violations’ — lie in the realm of subatomic physics. Such tiny differences would never show up in these biochemical experiments, says Benner. (He is also interested in making DNA that can avoid unwanted degradation by natural enzymes or viruses, but rather than using mirror-DNA, he has created artificial DNA with non-natural building blocks.)


Church’s ultimate goal, to make a mirror-image cell, faces enormous challenges. In nature, RNA is translated into proteins by the ribosome, a complex molecular machine. “Reconstructing a mirror-image of the ribosome would be a daunting task,” says Zhu. Instead, Church is trying to mutate a normal ribosome so that it can handle mirror-RNA.


Church says that it is anyone’s guess as to which approach might pay off. But he notes that a growing number of researchers are working on looking-glass versions of biochemical processes. “For a while it was a non-field,” says Church. “But now it seems very vibrant.”


No comment yet.
Scooped by Dr. Stefan Gruenwald!

Scientists hold closed meeting to discuss building a human genome from scratch

Scientists hold closed meeting to discuss building a human genome from scratch | Amazing Science |

More than 130 scientists, lawyers, entrepreneurs, and government officials from five continents gathered at Harvard this week for an “exploratory” meeting to discuss the topic of creating genomes from scratch — including, but not limited to, those of humans, said George Church, Harvard geneticist and co-organizer of the meeting.  The meeting was closed to the press, which drew the ire of prominent academics.


Synthesizing genomes involves building them from the ground up — chemically combining molecules to create DNA. Similar work by Craig Venter in 2010 created what was hailed as the first synthetic cell, a bacterium with a comparatively small genome.


In recent months, Church has been vocal in saying that the much-hyped genome-editing technology called CRISPR, which is only a few years old and which he helped develop, would soon be obsolete. Instead of changing existing genomes through CRISPR, Church has said, scientists could build exactly the genomes they want from scratch, by stringing together off-the-shelf DNA letters.


The topic is a heavy one, touching on fundamental philosophical questions of meaning and being. If we can build a synthetic genome — and eventually, a creature — from the ground up, then what does it mean to be human?


“This idea is an enormous step for the human species, and it shouldn’t be discussed only behind closed doors,” said Laurie Zoloth, a professor of religious studies, bioethics, and medical humanities at Northwestern University.


In response, she co-authored an article with Drew Endy, a bioengineering professor at Stanford University, calling for broader conversations around the research.


Church said that the meeting was originally going to be “an open meeting with lots of journalists engaged.” It was supposed to be accompanied by a peer-reviewed article on the topic. But, he said, the journal (which Church declined to identify) wanted the paper to include more information about the ethical, social, and legal components of synthesizing genomes — things that were discussed at the meeting.

No comment yet.
Scooped by Dr. Stefan Gruenwald!

Scientists Unveil A Novel Genome Editing Technique Similar To CRISPR-CAS

Scientists Unveil A Novel Genome Editing Technique Similar To CRISPR-CAS | Amazing Science |

The CRISPR/Cas9 system is currently the technique in genome editing. Thanks to recent developments in the CRISPR genome editing system, we are able to alter DNA with unprecedented precision and accuracy. Ultimately, this revolutionary genome editing technique allows us to modify any region of the genome of any species—without harming other genes. But more than that, we are able to edit these genes at just a fraction of the cost of previous methods.


It has utterly revolutionized gene editing. However, a team of researchers has just developed a new approach that just might prove to be as efficient and effective as the current standard.

In a study published in Nature Biotechnology, researchers from Chunyu Han’s lab have developed a novel genome editing technique basically just like CRISPR.


According to the report, the method is based on the Natronobacterium gregoryi Argonaute (NgAgo), a DNA-guided endonuclease that’s similar to Cas9, the endonuclease of CRISPR. These are a specific type of protein, otherwise known as restriction enzymes, that are responsible for cutting DNA at specific locations. Remarkably, the study shows that NgAgo is suitable for genome editing in human cells.


The team asserts that their study has a number of key differences between NgAgo and Cas9, where the former is at the advantage. They claim that that the method appears to have a low tolerance to guide-target mismatches, leading to a high efficiency in editing:


  • One of these is that NgAgo does not need to be followed by a protospacer-adjacent motif (PAM), a DNA sequence seen in Cas9. Notably, Cas9 will not successfully bind or cleave a target DNA sequence if this is not followed by the PAM (as it is responsible for the protein to differentiate CRISPR DNA from target DNA).
  • Another benefit is that the loading temperature of NgAgo is found to be at 55°C and not at Cas9’s 37°C. This shows that this could be another option for genome editing at conditions such as this. Also, at this temperature, the method follows a “one-guide-faithful” rule, that is, NgAgo cannot swap target DNA with other free DNA, minimizing off-target effects.


Though there has yet to be an extensive side-by-side comparison of the two enzymes, NgAgo and Cas9 appear to have similar efficiencies. The authors report that their tests with 47 guides targeting 8 human genes, the results showed a 21% to 41% efficiency.

No comment yet.
Scooped by Dr. Stefan Gruenwald!

Making Virus Sensors Cheap and Simple: New Method Detects Single Viruses

Making Virus Sensors Cheap and Simple: New Method Detects Single Viruses | Amazing Science |

Although the technique presently works on just one virus, scientists say it could be adapted to detect a range of viruses that plague humans including Ebola, Zika and HIV.


"The ultimate goal is to build a cheap, easy-to-use device to take into the field and measure the presence of a virus like Ebola in people on the spot," says Jeffrey Dick, a chemistry graduate student and co-lead author of the study. "While we are still pretty far from this, this work is a leap in the right direction."


The new method is highly specific, meaning it is only sensitive to one type of virus, filtering out possible false negatives caused by other viruses or contaminants. There are two other commonly used methods for detecting viruses in biological samples, but they have drawbacks. One requires a much higher concentration of viruses, and the other requires samples to be purified to remove contaminants. The new method, however, can be used with urine straight from a person or animal.


The researchers demonstrated their new technique on a virus that belongs to the herpesvirus family, called murine cytomegalovirus (MCMV). To detect individual viruses, the team places an electrode — a wire that conducts electricity, in this case, one that is thinner than a human cell — in a sample of mouse urine. They then add to the urine some special molecules made up of enzymes and antibodies that naturally stick to the virus of interest. When all three stick together and then bump into the electrode, there's a spike in electric current that can be easily detected.


The researchers say their new method still needs refinement. For example, the electrodes become less sensitive over time because a host of other naturally occurring compounds stick to them, leaving less surface area for viruses to interact with them. To be practical, the process will also need to be engineered into a compact and rugged device that can operate in a range of real-world environments.


No comment yet.
Rescooped by Dr. Stefan Gruenwald from Alzheimer's Disease R&D Review!

Biochemistry and Cell Biology of Tau in Neurofibrillary Degeneration

Biochemistry and Cell Biology of Tau in Neurofibrillary Degeneration | Amazing Science |

The tau protein is a subunit of one of the major hallmarks of Alzheimer disease (AD), the neurofibrillary tangles, and is therefore of major interest as an indicator of disease mechanisms. Many of the unusual properties of Tau can be explained by its nature as a natively unfolded protein. Examples are the large number of structural conformations and biochemical modifications (phosphorylation, proteolysis, glycosylation, and others), the multitude of interaction partners (mainly microtubules, but also other cytoskeletal proteins, kinases, and phosphatases, motor proteins, chaperones, and membrane proteins). The pathological aggregation of Tau is counterintuitive, given its high solubility, but can be rationalized by short hydrophobic motifs forming β structures. The aggregation of Tau is toxic in cell and animal models, but can be reversed by suppressing expression or by aggregation inhibitors. This review summarizes some of the structural, biochemical, and cell biological properties of Tau and Tau fibers. Further aspects of Tau as a diagnostic marker and therapeutic target, its involvement in other Tau-based diseases, and its histopathology are covered by other chapters in this volume.

Via Krishan Maggon
Krishan Maggon 's curator insight, May 18, 2:01 AM
Cold Spring Harb Perspect Med. 2012 Jul; 2(7): a006247. 
doi: 10.1101/cshperspect.a006247 PMCID: PMC3385935 

Biochemistry and Cell Biology of Tau Protein in Neurofibrillary Degeneration 

Eva-Maria Mandelkow and Eckhard Mandelkow

Image   Visualization of Tau and kinesin bound to microtubules.
Scooped by Dr. Stefan Gruenwald!

By the year 2040, embryo selection could replace sex as the way to make babies

By the year 2040, embryo selection could replace sex as the way to make babies | Amazing Science |

Human reproduction is about to undergo a radical shift. Embryo selection, in connection with in-vitro fertilization (IVF), will help our species eliminate many genetic diseases, extend healthy lifespans, and enhance people’s overall well-being. Within 20 years, I predict that it will supplant sex as the way large numbers of us conceive of our children. But while the embryo selection revolution will do a lot of good, it will also raise thorny ethical questions about diversity, equality and what it means to be human–questions we are woefully unprepared to address.


IVF for humans has been around since 1978, the year Louise Brown, the first so-called “test-tube baby,” was born in the UK. Since then, nearly six million infants around the world have been conceived via IVF, with the procedure growing in popularity each year. Starting in the 1990s, doctors began using preimplantation genetic screening (PGS) to extract cells from early-stage embryos and screen them for simple genetic diseases.


Over time, many genetic diseases will come to be seen as preventable parental lifestyle choices rather than bad luck. At present, over a thousand such diseases, including cystic fibrosis, Huntington’s disease, Tay-Sachs, sickle-cell anemia, and Duchenne muscular dystrophy, can be screened during PGS and the list is growing constantly. With this information, parents using IVF and PGS can select embryos not carrying those diseases if they choose to do so. Some jurisdictions, including the US, Mexico, Italy, and Thailand, also allow parents to select the gender of their future children.


These are still the early days of PGS. The process of linking single gene mutations to specific diseases has been slow and painstaking, but also relatively straightforward. As increasingly more people have their full genomes sequenced, an essential foundation for the future of personalized medicine, scientists will be able to uncover and screen for genetic and epigenetic patterns underpinning far more genetically complex diseases like epilepsy and type 1 diabetes.


As the PGS procedure improves and the number of diseases it prevents increases, I foresee that growing numbers of parents will decide to use assisted reproduction technologies when conceiving children. Over time, many genetic diseases will come to be seen as preventable parental lifestyle choices rather than bad luck. People will be free to opt out of laboratory-managed conception for religious, ideological, or economic reasons—or in fits of passion.


But having children through IVF and embryo selection will become the norm for parents of all ages and genetic predispositions. We’ll still have sex for most of the wonderful reasons we do now, just not to have babies. Governments and insurance companies will have strong incentives to cover the expense of IVF and embryo screening.


In the few countries like Australia, France, Israel, and Sweden, where assisted reproduction is covered by national health plans, the popular shift toward managed conception will not pose challenging questions of socio-economic equity. In other countries where the cost of IVF and PGS remains high—the procedures currently cost up to $20,000 in the US—the equity challenge will be greater. And in the poorest countries, IVF and PGS may not be available at all.


But as IVF and PGS become more widely accepted, the cost will go down and access percentages will go up. In many countries, governments and insurance companies will have strong incentives to cover the expense of IVF and embryo screening. This cost will be far less than that of providing lifetime care for all the children born with preventable genetic diseases in the absence of screening. Another option would be pre-natal screening of embryos during pregnancy, a far more morally fraught process with significantly fewer benefits.


Even as the procedures become more prevalent, IVF and PGS will not be without risk. Egg extraction can be extremely painful and sometimes even dangerous for women. Early-stage embryos can be damaged during the biopsy process, and up to a fifth of the embryos may not survive cryogenic freezing prior to implantation. The process can also be expensive, time-consuming, and stressful for parents. And a preliminary study released in the Journal of the American Medical Association (JAMA) earlier this year suggested that children born from IVF may be slightly more likely to carry certain birth defects than their non-IVF peers.


No comment yet.