Syndicate content

Archive - 2014

December 10th

New Technique Permits Rapid, Large-Scale Studies of Gene Function

Using a gene-editing system originally developed to delete specific genes, MIT researchers have now shown that they can reliably turn on any gene of their choosing in living cells. This new application for the CRISPR/Cas9 gene-editing system should allow scientists to more easily determine the function of individual genes, according to Dr. Feng Zhang, the W.M. Keck Career Development Professor in Biomedical Engineering in MIT’s Departments of Brain and Cognitive Sciences and Biological Engineering, and a member of the Broad Institute and MIT’s McGovern Institute for Brain Research. This approach also enables rapid functional screens of the entire genome, allowing scientists to identify genes involved in particular diseases. In a study published online on December 10, 2014 in Nature, Dr. Zhang and colleagues identified several genes that help melanoma cells become resistant to a cancer drug. Silvana Konermann, a graduate student in Dr. Zhang’s lab, and Dr. Mark Brigham, a McGovern Institute postdoc, are the paper’s lead authors. The CRISPR system relies on cellular machinery that bacteria use to defend themselves from viral infection. Researchers have previously harnessed this cellular system to create gene-editing complexes that include a DNA-cutting enzyme called Cas9 bound to a short RNA guide strand that is programmed to bind to a specific genome sequence, telling Cas9 where to make its cut. In the past two years, scientists have developed Cas9 as a tool for turning genes off or replacing them with a different version. In the new study, Dr. Zhang and colleagues engineered the Cas9 system to turn genes on, rather than knock them out.

TriLink BioTech Secures Contract for the Synthesis of Ebola Vaccine

In a December 10, 2014 press release, TriLink BioTechnologies (http://www.trilinkbiotech.com), a leader in manufacturing high-quality nucleic acids, today announced that it secured a contract with Battelle for the manufacture of mRNA to support vaccine development against filoviruses. The contract is in support of a project conducted by Medical Countermeasure Systems (MCS) – Joint Vaccine Acquisition Program (JVAP). MCS-JVAP works in conjunction with the Department of Defense to advance development, testing, FDA licensing, production, and storage of biological defense vaccines. The overall goal of the MCS-JVAP project is to create a trivalent vaccine effective against aerosolized exposure to Ebola Sudan, Ebola Zaire, and Marburg viruses. These viruses are highly lethal and may be used as biological warfare agents. Currently there are limited measures to fight against filovirus infections. TriLink’s role is to synthesize the mRNA needed for preclinical studies and to scale up the process in preparation for the synthesis of clinical grade material. "We are very excited to have been awarded this contract with Battelle for the MCS-JVAP project. TriLink is well known for our expertise in modified nucleic acid chemistry and mRNA manufacturing. This, coupled with our experience in the production of alphavirus replicons aligns well with the fundamental needs of this research, " said TriLink President and CEO, Dr. Richard Hogrefe. “Because we are a pharmaceutical-grade GMP manufacturer, we will be able to see this project into the clinic.” The project is sponsored by the Defense Technical Information Center. ATTN: DTIC-AI, B723 John J. Kingman Rd., Ste 0944, Fort Belvoir, VA 22060-6218.

New Drug Combination for Advanced Breast Cancer Delays Disease Progression

A new combination of cancer drugs delayed disease progression for patients with hormone-receptor-positive metastatic breast cancer, according to a multi-center phase II trial. The findings of the randomized study (S6-03) were to be presented on December 12. 2014 at the 2014 San Antonio Breast Cancer Symposium, held December 9-13, 2014, by Dr. Kerin Adelson, assistant professor of medical oncology at Yale Cancer Center and chief quality officer at Smilow Cancer Hospital at Yale-New Haven. The trial enrolled 118 post-menopausal women with metastatic hormone-receptor-positive breast cancer whose cancer continued to progress after being treated with an aromatase inhibitor. The study, based on work done by Dr. Doris Germain of Mt. Sinai Hospital in New York, found that the combination of the drugs bortezomib and fulvestrant — versus fulvestrant alone — doubled the rate of survival at 12 months and reduced the chance of cancer progression overall. Bortezomib, used most commonly in treating multiple myeloma, is a proteasome inhibitor that prevents cancer cells from clearing toxic material. Fulvestrant causes clumping of the estrogen-receptor protein. When bortezomib blocks the ability of the cell to clear these protein clumps, they grow larger and become toxic to the cancer cells. This, in turn, amplifies the effectiveness of fulvestrant, a drug commonly used in this subset of patients. The drug combination doubled the number of patients whose cancer had not progressed after one year from 14% to 28%, according to Dr. Adelson.

December 9th

Prion Misfolding Can Be Reversed by Yeast

Yeast cells can sometimes reverse the protein misfolding and clumping associated with diseases such as Alzheimer's, according to new research from the University of Arizona (UA). The new finding contradicts the idea that once prion proteins have changed into the shape that aggregates, the change is irreversible. "It's believed that when these aggregates arise that cells cannot get rid of them," said Dr. Tricia Serio, UA professor and head of the department of molecular and cellular biology. "We've shown that's not the case. Cells can clear themselves of these aggregates." Prions are proteins that change into a shape that triggers their neighbors to change, also. In that new form, the proteins cluster. The aggregates, called amyloids, are associated with diseases including Alzheimer's, Huntington's and Parkinson's. "The prion protein is kind of like Dr. Jekyll and Mr. Hyde," said Dr. Serio, senior author of the paper published today in the open-access journal eLife. "When you get Hyde, all the prion protein that gets made after that is folded in that bad way." For yeast, having clumps of amyloid is not fatal. Dr. Serio and her students exposed amyloid-containing cells of baker's yeast to 104 degrees F (40 degrees C), a temperature that would be a high fever in a human. When exposed to that environment, the cells activated a stress response that changed the clumping proteins back to the no-clumping shape. The finding suggests artificially inducing stress responses may one day help develop treatments for diseases associated with misfolded prion proteins, Dr. Serio said. "People are trying to develop therapeutics that will artificially induce stress responses," she said. "Our work serves as a proof of principal that it's a fruitful path to follow."

Ancient Parchment Provides DNA Clues to Agricultural Development Over Centuries

Millions of documents stored in archives could provide scientists with the key to tracing agricultural development across the centuries, according to new research completed at Trinity College Dublin in Ireland and the University of York in the UK. Amazingly, thanks to increasingly progressive genetic sequencing techniques, the all-important historical tales these documents tell are no longer confined to their texts; now, vital information also comes from the DNA of the parchment on which they are written. Researchers used these state-of-the-art scientific techniques to extract ancient DNA and protein from tiny samples of parchment from documents from the late 17th and late 18th centuries. The resulting information enabled them to establish the type of animals from which the parchment was made, which, when compared to genomes of their modern equivalents, provides key information as to how agricultural expansion shaped the genetic diversity of these animals. This information therefore gives the scientists an unrivalled resource to analyse the development of livestock husbandry across the centuries. The research was published online on ecember 8, 2014 in the international, peer-reviewed journal Philosophical Transactions of the Royal Society B. Professor of Population Genetics at Trinity College Dublin, Dr. Daniel Bradley, said: "This pilot project suggests that parchments are an amazing resource for genetic studies that consider agricultural development over the centuries. There must be millions stored away in libraries, archives, solicitors' offices, and even in our own attics.

Zone in with Zon--Broccoli and Autism Spectrum Disorder

Dr. Gerald Zon’s latest “Zone in with Zon” blog post, dated December 8, 2014, and published by TriLink BioTechnologies of San Diego, is entitled, “Broccoli May Reduce the Symptoms of Autism.” Although initially skeptical, Dr. Zon was persuaded to investigate the assertion because autism is such a common and difficult disorder and because the ABC News report (“Broccoli Sprout Extract May Help Curb Autism Symptoms”) referred to a supportive article in PNAS, a highly reputable scientific journal. In his blog, Dr. Zon first describes what autism is, saying that “autism is more accurately referred to as “autism spectrum disorder” (ASD) because it covers a wide range of complex neurodevelopment disorders, characterized by social impairments, communication difficulties, and restricted, repetitive, and stereotyped patterns of behavior. Classical ASD is the most severe form of ASD, while other conditions along the spectrum include a milder form known as Asperger syndrome, as well as childhood disintegrative disorder and pervasive developmental disorder not otherwise specified (PDD-NOS). Although ASD varies significantly in character and severity, it occurs in all ethnic and socioeconomic groups and affects every age group. Experts estimate that 1 out of 68 persons have an ASD. Interestingly, males are four times more likely to have an ASD than females.” With regard to the causes of autism, Dr. Zon notes that scientists are still not sure what causes ASD, although there seems to be agreement that both genetics and environment play roles. He notes that “thankfully for many children, symptoms improve with treatment and with age; however, children whose language skills regress early in life—before the age of 3—appear to have a higher than normal risk of developing epilepsy or seizure-like brain activity.”

Extract of Irish Potatoes Reduces Weight Gain to Surprising Extent

Take a look in your pantry: the miracle ingredient for fighting obesity may already be there. A simple potato extract may limit weight gain from a diet that is high in fat and refined carbohydrates, according to scientists at McGill University. The results of their recent study were so surprising that the investigators repeated the experiment just to be sure. Investigators fed mice an obesity-inducing diet for 10 weeks. The results soon appeared on the scale: mice that started out weighing on average 25 grams put on about 16 grams. But mice that consumed the same diet but with a potato extract gained much less weight: only 7 more grams. The benefits of the extract are due to its high concentration of polyphenols, a beneficial chemical component from the fruits and vegetables we eat. “We were astonished by the results,” said Professor Luis Agellon, one of the study’s authors. “We thought this can’t be right – in fact, we ran the experiment again using a different batch of extract prepared from potatoes grown in another season, just to be certain.” The rate of obesity due to over-eating continues to rise in Canada, affecting 1 in every 4 adults. Obesity increases the risk of cardiovascular disease and cancer. According to this study, potato extracts could be a solution for preventing both obesity and type 2 diabetes. The study was published in the November 2014 issue of Molecular Nutrition & Food Research. “The daily dose of extract comes from 30 potatoes, but of course we don’t advise anyone to eat 30 potatoes a day,” says Dr. Stan Kubow, principal author of the study, “as that would be an enormous number of calories.” What the investigators envisage instead is making the extract available as a dietary supplement or simply as a cooking ingredient to be added in the kitchen.

SNAP-Tagging Technique Provides Unprecedentedly Detailed Images of Mouse Neurons in Vivo

Scientists can now explore nerves in mice in much greater detail than ever before, thanks to a new approach developed by scientists at the European Molecular Biology Laboratory (EMBL) in Monterotondo, Italy, applied for the first time to neurons in living mice. The work, published online on December 8, 2014 in Nature Methods, enables researchers to easily use artificial tags, broadening the range of what they can study and vastly increasing image resolution. “Already we’ve been able to see things that we couldn’t see before,” says Dr. Paul Heppenstall from EMBL, who led the research. “Structures such as nerves arranged around a hair on the skin; we can now seethem under the microscope, just as they were presumed to be. The technique, called SNAP-tagging, had been used for about a decade in studies using cell cultures – cells grown in a lab dish – but Dr. Heppenstall’s group is the first to apply it to neurons in living mice. It allows researchers to use virtually any labels they want, making it easier to overcome the challenges that often come with studying complex tissues and animals. To study nerves in the skin, for instance, Dr. Heppenstall’s lab can employ artificial dyes that are small enough to cross the barrier posed by the skin itself, and stand out better from the skin’s natural fluorescence. And because these are artificial, custom-made tags, they can be designed to do more than just highlight particular structures. Scientists can produce tags that destroy certain structures or cells, for instance.

New Insight into Risk of Ankylosing Spondylitis

Scientists at the University of Southampton have discovered variations in an enzyme belonging to the immune system that leaves individuals susceptible to ankylosing spondylitis. The variation in ERAP1 can be detected by genetic testing which, if available, could lead to people becoming aware of the risk of the condition earlier. Ankylosing spondylitis is a chronic inflammatory disease which mainly affects joints in the spine. In severe cases, it can eventually cause complete fusion and rigidity of the spine, called "Bamboo spine." It tends to first develop in teenagers and young adults with most cases first starting in people aged 20-30. Ankylosing spondylitis is around three times more common in men than in women and there are around 200,000 people in the UK who have been diagnosed with the condition. Although there is currently no cure, treatments and medications can reduce symptoms and pain, and very early diagnosis may even help to slow progression of the disease. It can take up to 10 years to make a diagnosis so a genetic test could revolutionise management of ankylosing apondylitis, the researchers say. Professor Tim Elliott, who led the study with Dr. Edd James at the University of Southampton, comments: "These natural variations in ERAP1, which are normally involved in T cell immunity, predispose individuals to ankylosing spondylitis. We have also discovered how variations in ERAP1 change its enzyme function - and this means that it might actually be a target for developing new drugs to treat ankylosing spondylitis.

Quail Gait Information May Inform Studies of Dinosaur Gait

Dinosaurs did it. Human beings and monkey do it. And even birds do it. They walk on two legs. And although humans occupy a special position amongst mammals as they have two legs, the upright gait is not reserved only for man. In the course of evolution many animals have developed the bipedal gait - the ability to walk on two legs. "Birds are moving forward on two legs as well, although they use a completely different technique from us humans," Dr. Emanuel Andrada from the Friedrich Schiller University in Jena, Germany, says. Human beings keep their upper bodies generally in an upright position and the body's center of gravity is directly above the legs. The bodies of birds on the other hand are horizontally forward-facing, which appears to be awkward at first glance. Hence the motion scientist analyzed - together with colleagues - which effect this posture has on the movement of their legs and on their stability when they walk. The first detailed analysis of its kind has now been published online on November 5, 2014 by the scientists in the Proceedings of the Royal Society B. To this end, the team had quails walking through a high-speed X-ray installation at varying speeds. While the installation monitored the movements of the animals meticulously, the scientists were able to measure the power at work in the birds’ legs. From this data, the Jena research team could develop a computer model of the whole motion sequence, which served to simulate and analyze the stability and the energy balance in connection to different gaits.