 Your new post is loading...
While digital technology is extremely good at solving certain problems, it often struggles with tasks that the human brain excels at. In a new study, scientists have leveraged brain-inspired connectivity between artificial neurons to solve a real-world problem of identifying mutations of a new viral species. In the September issue of the journal Nature, scientists from Texas A&M University, Hewlett Packard Labs and Stanford University have described a new nanodevice that acts almost identically to a brain cell. Furthermore, they have shown that these synthetic brain cells can be joined together to form intricate networks that can then solve problems in a brain-like manner. "This is the first study where we have been able to emulate a neuron with just a single nanoscale device, which would otherwise need hundreds of transistors," said Dr. R. Stanley Williams, senior author on the study and professor in the Department of Electrical and Computer Engineering. "We have also been able to successfully use networks of our artificial neurons to solve toy versions of a real-world problem that is computationally intense even for the most sophisticated digital technologies." In particular, the researchers have demonstrated proof of concept that their brain-inspired system can identify possible mutations in a virus, which is highly relevant for ensuring the efficacy of vaccines and medications for strains exhibiting genetic diversity. Over the past decades, digital technologies have become smaller and faster largely because of the advancements in transistor technology. However, these critical circuit components are fast approaching their limit of how small they can be built, initiating a global effort to find a new type of technology that can supplement, if not replace, transistors. In addition to this "scaling-down" problem, transistor-based digital technologies have other well-known challenges. For example, they struggle at finding optimal solutions when presented with large sets of data. "Let's take a familiar example of finding the shortest route from your office to your home. If you have to make a single stop, it's a fairly easy problem to solve. But if for some reason you need to make 15 stops in between, you have 43 billion routes to choose from," said Dr. Suhas Kumar, lead author on the study and researcher at Hewlett Packard Labs. "This is now an optimization problem, and current computers are rather inept at solving it." Kumar added that another arduous task for digital machines is pattern recognition, such as identifying a face as the same regardless of viewpoint or recognizing a familiar voice buried within a din of sounds. But tasks that can send digital machines into a computational tizzy are ones at which the brain excels. In fact, brains are not just quick at recognition and optimization problems, but they also consume far less energy than digital systems. Hence, by mimicking how the brain solves these types of tasks, Williams said brain-inspired or neuromorphic systems could potentially overcome some of the computational hurdles faced by current digital technologies. To build the fundamental building block of the brain or a neuron, the researchers assembled a synthetic nanoscale device consisting of layers of different inorganic materials, each with a unique function. However, they said the real magic happens in the thin layer made of the compound niobium dioxide. When a small voltage is applied to this region, its temperature begins to increase. But when the temperature reaches a critical value, niobium dioxide undergoes a quick change in personality, turning from an insulator to a conductor. But as it begins to conduct electric currents, its temperature drops and niobium dioxide switches back to being an insulator. These back-and-forth transitions enable the synthetic devices to generate a pulse of electrical current that closely resembles the profile of electrical spikes, or action potentials, produced by biological neurons. Further, by changing the voltage across their synthetic neurons, the researchers reproduced a rich range of neuronal behaviors observed in the brain, such as sustained, burst and chaotic firing of electrical spikes. "Capturing the dynamical behavior of neurons is a key goal for brain-inspired computers," said Kumar. "Altogether, we were able to recreate around 15 types of neuronal firing profiles, all using a single electrical component and at much lower energies compared to transistor-based circuits."
Most antibiotics in use today are based on natural molecules produced by bacteria—and given the rise of antibiotic resistance, there’s an urgent need to find more of them. Yet coaxing bacteria to produce new antibiotics is a tricky proposition. Most bacteria won’t grow in the lab. And even when they do, most of the genes that cause them to churn out molecules with antibiotic properties never get switched on. The researchers placed tiny droplets of 25 newly discovered antibiotics on a carpet of beta-lactam resistant S. aureus. They identified two compounds that generated circles of dead bacteria (dark spots) around each droplet. Researchers at The Rockefeller University have found a way around these problems, however. By using computational methods to identify which genes in a microbe’s genome ought to produce antibiotic compounds and then synthesizing those compounds themselves, they were able to discover two promising new antibiotics without having to culture a single bacterium. The team, which was led by Sean Brady, head of the Laboratory of Genetically Encoded Small Molecules, began by trawling publicly available databases for the genomes of bacteria that reside in the human body. They then used specialized computer software to scan hundreds of those genomes for clusters of genes that were likely to produce molecules known as non-ribosomal peptides that form the basis of many antibiotics. They also used the software to predict the chemical structures of the molecules that the gene clusters ought to produce. The software initially identified 57 potentially useful gene clusters, which the researchers winnowed down to 30. Brady and his colleagues then used a method called solid-phase peptide synthesis to manufacture 25 different chemical compounds. By testing those compounds against human pathogens, the researchers successfully identified two closely related antibiotics, which they dubbed humimycin A and humimycin B. Both are found in a family of bacteria called Rhodococcus—microbes that had never yielded anything resembling the humimycins when cultured using traditional laboratory techniques. The humimycins proved especially effective against Staphylococcus and Streptococcus bacteria, which can cause dangerous infections in humans and tend to grow resistant to various antibiotics. Further experiments suggested that the humimycins work by inhibiting an enzyme that bacteria use to build their cell walls—and once that cell-wall building pathway is interrupted, the bacteria die.
Via Integrated DNA Technologies
Twist Bioscience dramatically scaled down the equipment for synthesizing DNA in a lab, making the process cheaper and faster. The stamp-sized wafers contain 100 microwells. Each of these contains 100 nanowells in which DNA can be synthesized.
AT TWIST BIOSCIENCE’S office in San Francisco, CEO Emily Leproust pulled out of her tote bag two things she carries around everywhere: a standard 96-well plastic plate ubiquitous in biology labs and her company’s invention, a silicon wafer studded with a similar number of nanowells.
Twist’s pitch is that it has dramatically scaled down the equipment for synthesizing DNA in a lab, making the process cheaper and faster. As Leproust gave her spiel, I looked from the jankety plastic plate, the size of two decks of cards side by side, to the sleek stamp-sized silicon wafer and politely nodded along. Then she handed me a magnifying lens to look down the wafer’s nanowells. Inside each nanowell was another 100 microscope holes.
That’s when I actually got it. The 96-well plate was not equivalent to the wafer, the entire plate was equivalent toone nanowell on the wafer. To put a number on it, traditional DNA synthesis machines can make one gene per 96-well plate; Twist’s machine can make 10,000 genes on a silicon wafer set the same size as the plate.
But who wants to order 10,000 genes? Until recently, that question might have been met with silence. “It was a lonely time,” says Leproust of her early fundraising efforts for Twist. Fast forward a couple years, though, and Twist has just signed a deal to sell at least 100 million letters of DNA—equivalent to tens of thousands of genes—to Ginkgo Bioworks, a synthetic biology outfit that inserts genes into yeast to make scents like rose oil or flavors like vanillin. Ginkgo is at the forefront of a wave of synthetic biology companies, bolstered by new gene-editing technologies like Crispr and investor interest.
“We’re Intel and Ginkgo is Microsoft,” says Leproust, which sounds exactly the kind of rhetoric you hear all the time in startupland. But her words reveal Twist’s specific ambition to be the driver behind synthetic biology innovations. Synthesizing genes in a lab allows biologists to design—down to the letter—the ones they want to test. Companies out there are already tinkering with DNA in various cells to create spider silk, cancer treatments, biodegradable plastic, diesel fuel—and Twist’s founders thinks the company can become the driving technology behind that new world.
Via Marko Dolinar
Researchers led by bioengineers at the University of California, San Diego have generated the most complete genome sequences from single E. coli cells and individual neurons from the human brain. The breakthrough comes from a new single-cell genome sequencing technique that confines genome amplification to fluid-filled wells with a volume of just 12 nanoliters. "Our preliminary data suggest that individual neurons from the same brain have different genetic compositions. This is a relatively new idea, and our approach will enable researchers to look at genomic differences between single cells with much finer detail," said Kun Zhang, a professor in the Department of Bioengineering at the UC San Diego Jacobs School of Engineering and the corresponding author on the paper. The researchers report that the genome sequences of single cells generated using the new approach exhibited comparatively little "amplification bias," which has been the most significant technological obstacle facing single-cell genome sequencing in the past decade. This bias refers to the fact that the amplification step is uneven, with different regions of a genome being copied different numbers of times. This imbalance complicates many downstream genomic analyses, including assembly of genomes from scratch and identifying DNA content variations among cells from the same individual. Sequencing the genomes of single cells is of great interest to researchers working in many different fields. For example, probing the genetic make-up of individual cells would help researchers identify and understand a wide range of organisms that cannot be easily grown in the lab from the bacteria that live within our digestive tracts and on our skin, to the microscopic organisms that live in ocean water. Single-cell genetic studies are also being used to study cancer cells, stem cells and the human brain, which is made up of cells that increasingly appear to have significant genomic diversity.
Deep sequencing was used to discover a novel rhabdovirus (Bas-Congo virus, or BASV) associated with a 2009 outbreak of 3 human cases of acute hemorrhagic fever in Mangala village, Democratic Republic of Congo (DRC), Africa. The cases, presenting over a 3-week period, were characterized by abrupt disease onset, high fever, mucosal hemorrhage, and, in two patients, death within 3 days. BASV was detected in an acute serum sample from the lone survivor at a concentration of 1.09×106 RNA copies/mL, and 98.2% of the genome was subsequently de novo assembled from ~140 million sequence reads. Phylogenetic analysis revealed that BASV is highly divergent and shares less than 34% amino acid identity with any other rhabdovirus. High convalescent neutralizing antibody titers of >1:1000 were detected in the survivor and an asymptomatic nurse directly caring for him, both of whom were health care workers, suggesting the potential for human-to-human transmission of BASV. The natural animal reservoir host or arthropod vector and precise mode of transmission for the virus remain unclear. BASV is an emerging human pathogen associated with acute hemorrhagic fever in Africa.
Grants of almost $19 million will help to develop technologies to dramatically reduce the cost of DNA sequencing, the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, has announced. During the past decade, DNA sequencing costs have fallen dramatically (see www.genome.gov/sequencingcosts), fueled by tools, technologies and process improvements developed by genomics researchers. In 2004, NHGRI launched the Advanced DNA Sequencing Technology Program to accelerate improvements in DNA sequencing technologies. By 2009, the program had surpassed its initial goal of producing high-quality genome sequences of roughly 6 billion base pairs — the amount of DNA found in humans and other mammals that receive roughly 3 billion base pairs from each of their parents — for $100,000 each. Today, the cost of sequencing a human genome using these next-generation DNA sequencing technologies has dipped to just under $8,000. Price is still one big hurdle in the way of widespread use of genomics in research and clinical care. Speed and accuracy are among other factors. The grants will attempt to address all of these challenges.
|
Vanderbilt engineers have developed a new method for duplicating DNA that makes devices small enough to hold in your hand that are capable of identifying infectious agents before symptoms appear. Imagine a “DNA photocopier” small enough to hold in your hand that could identify the bacteria or virus causing an infection even before the symptoms appear. This possibility is raised by a fundamentally new method for controlling a powerful but finicky process called the polymerase chain reaction or PCR. PCR was developed in 1983 by Kary Mullis, who received the Nobel Prize for his invention. It is generally considered one of the most important advances in the field of molecular biology because it can make billions of identical copies of small segments of DNA so they can be used in molecular and genetic analyses. Vanderbilt University biomedical engineers Nicholas Adams and Frederick Haselton came up with an out-of-the-box idea, which they call adaptive PCR. It uses left-handed DNA (L-DNA) to monitor and control the molecular reactions that take place in the PCR process. Left-handed DNA is the mirror image of the DNA found in all living things. It has the same physical properties as regular, right-handed DNA but it does not participate in most biological reactions. As a result, when fluorescently tagged L-DNA is added to a PCR sample, it behaves in an identical way to the regular DNA and provides a fluorescent light signal that reports information about the molecular reactions taking place and can be used to control them. In order to test their idea, Adams and Haselton recruited Research Assistant Professor of Physics William Gabella to create a working prototype of an adaptive PCR machine and then they tested it extensively with the assistance of biomedical engineering undergraduate Austin Hardcastle. A description of the technique and their test results are described in the paper “Adaptive PCR Based on Hybridization Sensing of Mirror-Image L-DNA” published in the journal Analytical Chemistry.
A group coordinated by the International School for Advanced Studies (SISSA) in Trieste has built a three-dimensional computer model of the human genome. The shape of DNA (as well as its sequence) significantly affects biological processes and is therefore crucial for understanding its function. This new study has provided a first three-dimensional, approximate but realistic, identikit of the human genome. Thanks to the characteristics of the new method, the structural reconstruction based on both experimental information and statistical methods will be refined as new experimental data become available. The study, carried out in collaboration with the University of Oslo, has just been published in Scientific Reports (a journal of the Nature group). Genome sequencing is a milestone in modern biology as it allows access to the entire “list of instructions” (the chemical sequence of genetic makeup) for the development and function of organisms. Sequencing the genome is a bit like writing down the exact order of the color of beads in a necklace: knowing how they are arranged along the thread gives us no indication as to the shape of the necklace. The shape of the DNA strand can be highly complex, given that the chromosomes are loosely arranged in an apparently chaotic tangle in the cell nucleus. Since the shape of chromosomes may have a decisive effect on their function, it is important that it should be characterized, in part because scientists think the DNA tangle in the nucleus is only apparently chaotic and that it has instead a specific “geography” for each tissue and stage of cell life. “Arriving at a precise description of the shape of the DNA tangle is unfortunately incredibly complicated”, explains Cristian Micheletti, SISSA professor and coordinator of the new study. “In our case, we used experimental data on ‘proximity pairs’”. “Imagine having to create a map of a city”, he explains, “based only on information like ‘the post office is opposite the station’, ‘the chemist is close to the gym’, ‘the fruit and vegetable market is near the football field’ and so on. If you have only a small number of such statements to go by, your map will be approximate and in some cases indeterminate. But if you have hundreds, thousands or even more, then your map will become increasingly precise and accurate. This is the logic we followed”. “Proximity pairs” therefore refers to information on the closeness of two points on the map. In the case of nuclear DNA, this information was provided by a technique (which Micheletti defines as “brilliant”) known as Hi-C, developed by North American research groups in 2010. In this chemical-physical technique, bits of genome located close to each another in the nucleus are tied together and then identified by their sequence. By collecting large numbers of these proximity pairs scientists discovered which points of the chromosomes lie close to each other in the nucleus. While this is today the most powerful technique for investigating DNA organisation in the nucleus, it is still inadequate for inferring its overall shape. “For this reason, we thought we would try to go ‘further’”, comments Micheletti.
Via Integrated DNA Technologies
Computer program crudely predicts a facial structure from genetic variations.
Researchers have now shown how 24 gene variants can be used to construct crude models of facial structure. Thus, leaving a hair at a crime scene could one day be as damning as leaving a photograph of your face. Researchers have developed a computer program that can create a crude three-dimensional (3D) model of a face from a DNA sample.
Using genes to predict eye and hair color is relatively easy. But the complex structure of the face makes it more valuable as a forensic tool — and more difficult to connect to genetic variation, says anthropologist Mark Shriver of Pennsylvania State University in University Park, who led the work, published today in PLOS Genetics1.
Shriver and his colleagues took high-resolution images of the faces of 592 people of mixed European and West African ancestry living in the United States, Brazil and Cape Verde. They used these images to create 3D models, laying a grid of more than 7,000 data points on the surface of the digital face and determining by how much particular points on a given face varied from the average: whether the nose was flatter, for instance, or the cheekbones wider. They had volunteers rate the faces on a scale of masculinity and femininity, as well as on perceived ethnicity.
Next, the authors compared the volunteers’ genomes to identify points at which the DNA differed by a single base, called a single nucleotide polymorphism (SNP). To narrow down the search, they focused on genes thought to be involved in facial development, such as those that shape the head in early embryonic development, and those that are mutated in disorders associated with features such as cleft palate. Then, taking into account the person’s sex and ancestry, they calculated the statistical likelihood that a given SNP was involved in determining a particular facial feature.
This pinpointed 24 SNPs across 20 genes that were significantly associated with facial shape. A computer program the team developed using the data can turn a DNA sequence from an unknown individual into a predictive 3D facial model (see 'Face to face'). Shriver says that the group is now trying to integrate more people and genes, and look at additional traits, such as hair texture and sex-specific differences.
For Venter life can be reduced to “protein robots” and “DNA machines” but he also believes that technology will unlock far more exotic opportunities for creating life. The title of the publication refers to the idea that we may be able to transmit DNA sequences found on Mars back to Earth (at the speed of light) to be replicated at home by biological printers. “I am confident that life once thrived on Mars and may well still exist there today,” writes Venter. “The day is not far off when we will be able to send a robotically controlled genome-sequencing unit in a probe to other planets to read the DNA sequence of any alien microbe life that may be there.” Venter’s ideas may sound like science fiction but he has achieved comparable feats in the past. Frustrated by what he viewed as slow government-led efforts to sequence the human genome in the 90s, Venter raised private capital to create a rival effort under the company name of Celera Fears that Venter and his backers would attempt to patent the genome spurred the US-led effort into action and global genes-race was sparked, with both sides eventually agreeing to announce their result one day apart in February 2001. Venter parted ways with Celera in 2002 and founded the J.Craig Venter institute in 2006. In 2010 he and his colleagues at the institute announced that they had created the world’s first synthetic organism. The team creating a bacterium genome from scratch and ‘watermarked’ it with custom DNA strings (these included an encoded email address) before transplanting it into another cell. The cell then began to reproduce, making it the first living species created by humanity. Although such pioneering work frequently raises ethical questions over the danger of humanity ‘playing God’, Venter writes that he is not concerned with such concerns. In ‘Life at the Speed of Light’ he writes: “My greatest fear is not the abuse of technology but that we will not use it at all.
When Mexican police found a body in the woods it was burned beyond recognition, its DNA too damaged to be used for identification. Luckily, investigators were able to extract DNA from elsewhere - the digestive systems of maggots that had been feeding on the body. This is the first time that human DNA from a maggot gut has been analysed in this way to successfully identify a victim in a legal case. Police suspected that the body was that of a woman who had been abducted 10 weeks earlier because they found her high-school graduation ring near the crime scene. But when forensic investigators failed to obtain a decent DNA sample from any of the body's tissues, they turned to a team of pathologists at the Autonomous University of Nuevo León in San Nicolás, Mexico. María de Lourdes Chávez-Briones, Marta Ortega-Martínez and their colleagues dissected three maggot larvae collected from the body and extracted the contents of their gastrointestinal tracts. The human DNA they isolated allowed them to determine that the body was female. They then performed a paternity test between this DNA and that of the abducted woman's father. It revealed a 99.7 per cent chance that she was his daughter
|
