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Archive - Jan 2014

January 20th

New Sequencing System from Illumina May Enable World’s First $1,000 Genomes

In a January 14, 2014 press release, Illumina, Inc. (NASDAQ:ILMN) announced that it had broken the ‘sound barrier’ of human genomics by enabling the $1,000 genome. This achievement is made possible by the Illumina’s new HiSeq X Ten Sequencing System. This platform includes dramatic technology breakthroughs that enable researchers to undertake studies of unprecedented scale by providing the throughput to sequence tens of thousands of human whole genomes in a single year in a single lab. Initial customers for the transformative HiSeq X Ten System include Macrogen, a global next-generation sequencing service organization based in Seoul, South Korea and its CLIA laboratory in Rockville, Maryland, the Broad Institute in Cambridge, Massachusetts, the world’s leading research institute in genomic medicine, and the Garvan Institute of Medical Research in Sydney, Australia, a world leader in biomedical research. “The sequencing capacity and economies of scale of the HiSeq X Ten facility will also allow Garvan to accelerate the introduction of clinical genomics and next-generation medicine in Australia,” said Professor John Mattick, Executive Director of the Garvan Institute of Medical Research. “We expect the HiSeq X Ten to underpin a new phase of collaboration between government, industry, and other medical research stakeholders.” “For the first time, it looks like it will be possible to deliver the $1,000 genome, which is tremendously exciting,” said Dr. Eric Lander, founding director of the Broad Institute and a professor of biology at MIT. “The HiSeq X Ten should give us the ability to analyze complete genomic information from huge sample populations.

January 18th

More Rigid Analogs of ADEPS Have Potent Antibiotic Activity

As concerns about bacterial resistance to antibiotics grow, researchers are racing to find new kinds of drugs to replace ones that are no longer effective. One promising new class of molecules called acyldepsipeptides — ADEPs — kills bacteria in a way that no marketed antibacterial drug does — by altering the pathway through which cells rid themselves of harmful proteins. Now, researchers from Brown University and the Massachusetts Institute of Technology have shown that giving the ADEPs more backbone can dramatically increase their biological potency. By modifying the structure of the ADEPs in ways that make them more rigid, the team prepared new ADEP analogs that are up to 1,200 times more potent than the naturally occurring molecule. A paper describing the research was published online on January 14, 2014 in the Journal of the American Chemical Society. “The work is significant because we have outlined and validated a strategy for the enhancing the potency of this promising class of antibacterial drug leads,” said Dr. Jason Sello, professor of chemistry at Brown and the paper’s senior author. “The molecules that we have synthesized are among the most potent antibacterial agents ever reported in the literature.” ADEPs kill bacteria by a mechanism that is distinct from all clinically available anti-bacterial drugs. They work by binding to a protein in bacterial cells that acts as a “cellular garbage disposal,” as Dr. Sello describes it. This barrel-shaped protein, called ClpP, breaks down proteins that are misfolded or damaged and could be harmful to the cell. However, when ClpP is bound by an ADEP, it’s no longer so selective about the proteins it degrades In essence, the binding by ADEP causes the garbage disposal to run amok and devour healthy proteins throughout the cell. For bacteria, a runaway ClpP is deadly.

Novel Biological Mechanism Relays Electrons Along Hemes in Proteins in Mineral-Breathing Bacteria

Researchers simulating how certain bacteria run electrical current through tiny molecular wires have discovered a secret that nature uses for electron travel. The results are key to understanding how the bacteria do chemistry in the ground, and will help researchers use these bacteria in microbial fuel cells, batteries, or for turning waste into electricity. Within the bacteria's protein-based wire, molecular groups called hemes communicate with each other to allow electrons to hop along the chain like stepping stones. The researchers found that evolution has set the protein up so that, generally, when the electron's drive to hop is high, the heme stepping stones are less tightly connected, like being farther apart; when the drive to hop is low, the hemes are more closely connected, like being closer together. The outcome is an even electron flow along the wire. This is the first time scientists have seen this evolutionary design principle for electron transport, the researchers reported online on January 2, 2014 in PNAS. "We were perplexed at how weak the thermodynamic driving force was between some of these hemes," said geochemist Dr. Kevin Rosso of the Department of Energy's Pacific Northwest National Laboratory. "But it turns out those pairs of hemes are essentially hugging each other. When the driving force is strong between hemes, they are only shaking hands. We've never seen this compensation scheme before, but it seems that the purpose is to allow the protein to transfer electrons with a steady flow along heme wires." Certain bacteria breathe using metal like people use oxygen. In the process, these bacteria steal electrons from carbon and ultimately transfer the electrons to metals or minerals in the ground.

Newly Discovered ATP Receptor Helps Plants Manage Environmental Change, Pests, and Wounds

ATP (adenosine triphosphate) is the main energy source inside a cell and is considered to be the high energy molecule that drives all life processes in animals, including humans. Outside the cell, membrane receptors that attract ATP drive muscle control, neurotransmission, inflammation, and development. Now, researchers at the University of Missouri (MU) have found, for the first time, the same receptor in plants and believe it to be a vital component in the way plants respond to dangers, including pests, environmental changes, and plant wounds. This discovery could lead to herbicides, fertilizers, and insect repellants that naturally work with plants to make them stronger. "Plants don't have ears to hear, fingers to feel, or eyes to see," said Dr. Gary Stacey an investigator in the MU Bond Life Sciences Center and professor of plant sciences in the College of Agriculture, Food and Natural Resources. "Plants use these chemical signals to determine if they are being preyed upon or if an environmental change is occurring that could be detrimental to the plant. We have evidence that when ATP is outside of the cell it is probably a central signal that controls the plant's ability to respond to a whole variety of stresses." Dr. Stacey and fellow researchers, graduate student Jeongmin Choi, and postdoctoral fellow Dr. Kiwamu Tanaka, screened 50,000 plants over two years to identify the ATP receptors. By isolating a key gene in the remaining plants, scientists found the receptor that aids in plant development and helps repair a plant during major events. "We believe that when a plant is wounded, ATP is released into the wound and triggers the gene expressions necessary for repair," Dr. Stacey said.

Bacterium “Breathes” Toxic Metals to Survive, Potential for Industry and Environment

Buried deep in the mud along the banks of a remote salt lake near Yosemite National Park are colonies of bacteria with an unusual property: they breathe a toxic metal to survive. Researchers from the University of Georgia discovered the bacteria on a recent field expedition to Mono Lake (image) in California, and their experiments with this unusual organism show that it may one day become a useful tool for industry and environmental protection. The bacteria use elements that are notoriously poisonous to humans, such as antimony and arsenic, in place of oxygen, an ability that lets them survive buried in the mud of a hot spring in this unique saline soda basin. "Just like humans breathe oxygen, these bacteria respire poisonous elements to survive," said Chris Abin, co-author of a paper describing the research published in the January 7, 2014 issue of Environmental Science & Technology and a doctoral candidate in microbiology. "It is particularly fond of arsenic, but it uses other related elements as well, and we think it may be possible to harness these natural abilities to make useful products out of different elements." Antimony, for example, is a naturally occurring silver-colored metal that is widely used by numerous industries to make plastics, vulcanized rubber, flame retardants, and a host of electronic components including solar cells and LEDs. To make these products, antimony must be converted into antimony trioxide, and this bacterium is capable of producing two very pure types of crystalline antimony trioxide perfectly suited for industry. Traditional chemical methods used to convert antimony ore into antimony trioxide can be expensive, time-consuming, and often create harmful byproducts.

Male Honey Bees More Susceptible Than Females to Widespread Intestinal Parasite

Gender differences in nature are common, including in humans. A research team from Bern, Switzerland has found that male European honey bees, or drones, are much more susceptible than female European honey bees, known as workers, to a fungal intestinal parasite called Nosema ceranae. Originally from Asia, Nosema ceranae has rapidly spread throughout the world in recent years, and may contribute to the high number of colony deaths now observed in many regions of the northern hemisphere. These findings demonstrate the delicate nature of male honey bees, which are important to honey bee colony reproduction, and its susceptibility to a well-distributed parasite. Honey bees are complex social organisms that demonstrate haploid-diploidy. The two female castes, workers and queens, are diploid, like humans. They contain two copies of each chromosome. Male honey bees, known as drones, on the other hand, are haploid and contain only one chromosome set. The haploid susceptibility hypothesis predicts that haploid males are more prone to disease compared to their diploid female counterparts because dominant genes on one chromosome copy have the opportunity to mask mutated genes on the other copy in diploid organisms. A research team from the Vetsuisse Faculty of the University of Bern in Switerland demonstrated in a January 17, 2014 online article in the open-access journal PLOS ONE that male honey bees are significantly more susceptible (they die sooner and have poor body condition) to an exotic fungal intestinal parasite called Nosema ceranae compared to female worker honey bees. The parasite, originally from Asia, has recently spread to have a near-global distribution during a period of high honey bee colony losses in many global regions.

January 17th

Scientists ID Evolutionary Switch in Regulation of Low Oxygen Response in Fungi; Possible Huge Clinical Impact

All but a few eukaryotes die without oxygen, and they respond dynamically to changes in the level of oxygen available to them. University College Dublin (UCD) scientists used genetic analysis to pinpoint an evolutionary switch in regulating response to low oxygen levels in fungi. One example of an ancient oxygen-requiring biochemical pathway in eukaryotes is the biosynthesis of sterols, producing cholesterol in animals and ergosterol in fungi. The mechanism regulating the sterol pathway is widely conserved between animals and fungi and centers on a protein family of transcription activators named the sterol regulatory element binding proteins (SREBPs), which form part of a sterol-sensing complex. However, in one group of fungi; the Saccharomycotina, which includes the model yeast Saccharomyces cerevisiae and the major pathogen Candida albicans, control of the sterol pathway has been taken over by an unrelated regulatory protein, Upc2. New research published in PLOS Genetics by UCD researchers, in collaboration with colleagues from AgroParisTech, France, and the University of Kansas, USA, used comparative genomic analysis to investigate the timing of the evolutionary switch from one regulatory mechanism to another; from SREBPs to Upc2. Led by Professor Geraldine Butler, UCD Conway Institute and UCD School of Biomolecular & Biomedical Science, the group found that one yeast species, Yarrowia lipolytica (image), is unique in that it contains both SREBP and Upc2 genes. Y. lipolytica is used in the biotechnology industry to produce lipids and lies at the base of the Saccharomycotina group. Using a mixture of genetic and biochemical analysis, the group showed that Upc2 is the main regulator of the hypoxic response in Y.

How Male Black Widow Avoids Appearing As Prey When Approaching Potential Mate

A team of Simon Fraser University (Canada) (SFU) biologists has found that male black widow spiders shake their abdomens to produce carefully pitched vibrations that let females know they have “come a-courting” and are not potential prey. The team’s research has just been published online on January 17, 2014 in the open-access journal Frontiers in Zoology. SFU graduate students Samantha Vibert and Catherine Scott, working with SFU biology professor Dr. Gerhard Gries, recorded the vibrations made by male black widow spiders (Latrodectus hesperus), hobo spiders (Tegenaria agrestis), and prey insects. Ms. Scott explains: “The web functions as an extension of the spider's exquisitely tuned sensory system, allowing her to very quickly detect and respond to prey coming into contact with her silk. This presents prospective mates with a real challenge when they first arrive at a female's web: they need to signal their presence and desirability, without triggering the female's predatory response.” The researchers found that the courtship vibrations of both species differed from those of prey, but that the very low-amplitude vibratory signals produced when male black widows shake their abdomens were particularly distinctive. “These 'whispers' may help to avoid potential attacks from the females they are wooing," explains Ms. Scott. [Press release] [Frontiers in Zoology article]

Scientists Find Possible Cure for Deadly Flesh-Eating Streptococcus Infection

Collaboration between the National University of Singapore (NUS) and The Hebrew University of Jerusalem (HUJ) on inflammation research may lead to a potential treatment for deadly bacterial infections. Scientists from the NUS-HUJ-CREATE Inflammation Research Programme based in Singapore have found that asparaginase (ASNASE) – the enzyme that degrades the amino acid asparagine and serves as a common chemotherapeutic agent – arrests Group A Streptococcus (GAS) growth in human blood and blocks bacteria’s proliferation, thus initiating a new potential treatment against deadly Streptococcal infections. These findings were published in the January 16, 2014 issue of the prestigious journal Cell. The research program is funded by the National Research Foundation, Prime Minister’s Office, Singapore, under its Campus for Research Excellence and Technological Enterprise (CREATE) program. The NUS-HUJ-CREATE Inflammation Research Program was established in 2011, and is focused on advancing an understanding of cellular and molecular mechanisms of inflammation of diseases prevalent in Asia, a field that is currently under-studied. GAS is a strict human pathogen that causes a wide range of infections, from mild to deadly. It can colonize the host without causing any symptoms, or cause mild infections of skin and trough such as pharyngitis. On the invasive end of the spectrum, GAS can cause life-threatening infections such as bacteremia, necrotizing fasciitis (commonly known as flesh-eating disease), and streptococcal toxic shock syndrome. Annually, disseminated GAS infections cause approximately 160,000 deaths globally and severe injuries to those infected.

Vitamin D Relaxes Blood Vessels, Affects Blood Pressure

It’s not just your mood that the dark months of winter can influence. Low levels of sunlight also mean lower levels of vitamin D in the body. Vitamin D deficiency can trigger a range of diseases, but until recently little was known about the exact biological mechanisms behind this. A research team at the University of Veterinary Medicine, Vienna, Austria, has now decrypted one of these unknown molecular mechanisms. Vitamin D regulates the elasticity of blood vessels and thus also affects blood pressure amplitude. The results were published in the January 2014 issue of Molecular Endocrinology. UV-B radiation in sunlight is the most important factor for the production of vitamin D, and that is why many people suffer from low levels of vitamin D during the winter months. Although certain foods do contain vitamin D, it is not usually possible to get an adequate supply of the vitamin from food. Many clinical studies have indicated that low vitamin D levels are related to cardiovascular disease such as high blood pressure, but also other diseases such as diabetes mellitus, autoimmune diseases, and even cancer. However, the underlying molecular mechanisms were unclear. The two primary authors of the Molecular Endocrinology article, molecular biologist Dr. Olena Andrukhova and medical doctor Svetlana Slavic, of the Institute of Physiology, Pathophysiology, and Biophysics at the Vetmeduni Vienna, found that prolonged vitamin D deficiency can stiffen blood vessels. Examining the aorta, an elastic blood vessel that expands with each pulse of blood and then constricts again, the researchers showed that vitamin D deficiency makes the vessel less flexible. Dr. Andrukhova explains in detail: "Vitamin D enhances the production of the enzyme eNOS (endothelial nitric oxide synthase) in the inner layer of blood vessels, the endothelium.