Tagged: EBOLA Toggle Comment Threads | Keyboard Shortcuts

  • richardmitnick 7:58 pm on June 6, 2017 Permalink | Reply
    Tags: Antibodies from Ebola survivor could lead to treatments and vaccines, , , EBOLA, , ,   

    From NIH: “Antibodies from Ebola survivor could lead to treatments and vaccines” 

    National Institutes of Health

    June 6, 2017
    Harrison Wein, Ph.D.

    1
    Colorized scanning electron micrograph of filamentous Ebola virus particles (green) attached to and budding from an infected cell (blue) (25,000x magnification).NIAID

    The 2013-16 Ebola outbreak in West Africa highlighted the need for an effective treatment or vaccine. Researchers have been making progress on several fronts, but many scientific and logistical challenges loom.

    Viruses from three of the five known ebolavirus species (Zaire, Sudan, and Bundibugyo) have caused large outbreaks in humans, and the other two (Reston and Tai Forest) cause severe disease in primates. The related Marburg and Ravn viruses also cause similar hemorrhagic fevers and serious outcomes in people. An ideal approach would target many, if not all, of the viruses in this family, called filoviruses.

    Scientists have searched for insights from natural antibodies, molecules produced by the immune system that bind to a specific substance, such as an invading virus. Antibodies recognize small, often unique, portions of viruses. Researchers previously discovered an antibody from a mouse that recognizes a common region among multiple ebolavirus species. The antibody proved protective in mouse models of infection.

    A team of academic, industry, and government scientists set out to find similar broadly protective human antibodies. The group was led by Dr. John M. Dye at the U.S. Army Medical Research Institute of Infectious Diseases, Dr. Kartik Chandran at Albert Einstein College of Medicine, and Dr. Zachary A. Bornholdt at Mapp Biopharmaceutical, Inc. Their work was funded in part by NIH’s National Institute of Allergy and Infectious Diseases (NIAID). Results appeared in Cell on May 18, 2017.

    The researchers surveyed 349 antibodies derived from the blood of one survivor of the West African Ebola outbreak, which was caused by the Zaire strain of ebolavirus. They searched for antibodies that could neutralize all five ebolavirus species. Two that they found of interest were called ADI-15878 and ADI-15742. Both protected human cells in the laboratory from becoming infected with the three ebolaviruses that cause outbreaks in humans. Neither, however, protected against the more distantly related filoviruses Lloviu or Marburg.

    In animal models of ebolavirus infection, the antibodies protected mice from the Zaire and Sudan ebolaviruses and ferrets from Bundibugyo ebolavirus. However, in ferrets treated with ADI-15742, the researchers found that the virus had developed a mutation that enabled it to escape the antibody’s effects.

    Further study showed that the antibodies recognize a section of a protein found on the surface of ebolaviruses called the GP fusion loop, which is critical for infection. The antibodies don’t prevent the viruses from being engulfed by cells. Rather, they are taken up along with the virus particles and neutralize the viruses as they are being processed within the cell.

    “Since it’s impossible to predict which of these agents will cause the next epidemic, it would be ideal to develop a single therapy that could treat or prevent infection caused by any known ebolavirus,” Bornholdt says. While much work still needs to be done, the identification of this vulnerable shared region on the surface of ebolaviruses is an important step toward creating effective treatments or vaccines.

    See the full article here .

    You can Help Stamp Out EBOLA.

    This WCG project runs at Scripps Institute


    Scripps

    Outsmart Ebola Together

    Visit World Community Grid (WCG). Download and install the BOINC software on which it runs. Attach to the Outsmart Ebola Together project. This will allow WCG to use your computer’s free CPU cycles to process computational data for the project.


    While you are at WCG and BOINC, check out the other very worthwhile projects running on this software. All project results are “open source”, free for the use of scientists world while to advance health and other issues of mankind.

    MyBOINC

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the nation’s medical research agency — making important discoveries that improve health and save lives.

     
  • richardmitnick 3:51 pm on December 23, 2016 Permalink | Reply
    Tags: , EBOLA, , New Ebola Vaccine Gives 100 Percent Protection,   

    From NYT: “New Ebola Vaccine Gives 100 Percent Protection” 

    New York Times

    The New York Times

    DEC. 22, 2016
    DONALD G. McNEIL Jr.

    1
    Health workers in November 2015 with Mibemba Soumah, infected by Ebola, at a treatment center in Conakry, Guinea. Credit Samuel Aranda for The New York Times.

    In a scientific triumph that will change the way the world fights a terrifying killer, an experimental Ebola vaccine tested on humans in the waning days of the West African epidemic has been shown to provide 100 percent protection against the lethal disease.

    The vaccine has not yet been approved by any regulatory authority, but it is considered so effective that an emergency stockpile of 300,000 doses has already been created for use should an outbreak flare up again.

    Since Ebola was discovered in the former Zaire in 1976, there have been many efforts to create a vaccine. All began with a sense of urgency but then petered out for lack of money. Although only about 1,600 people died of Ebola over those years, the grotesque nature their deaths — copious hemorrhaging from every orifice — has lent the disease a frightening reputation.

    Ultimately, only the huge, explosive 2014 outbreak that took 11,000 lives in Africa and spread overseas, reaching a handful of people in Europe and the United States, provided the political and economic drive to make an effective vaccine.

    The test results of the trial in Guinea were released Thursday in The Lancet.

    The vaccine was not ready in time to stop the outbreak, which probably began in a hollow, bat-filled tree in Guinea and swept Liberia and Sierra Leone before being defeated. But the prospect of a vaccine stockpile now has brought optimism among public health experts.

    “While these compelling results come too late for those who lost their lives during West Africa’s Ebola epidemic, they show that when the next outbreak hits, we will not be defenseless,” said Marie-Paule Kieny, the World Health Organization’s assistant director-general for health systems and innovation and the study’s lead author. “The world can’t afford the confusion and human disaster that came with the last epidemic.”

    The vaccine opens up new, faster, more efficient ways to encircle and strangle the virus. The many small Ebola outbreaks that occurred between 1976 and 2014 were all stopped in remote villages by laborious methods: medical teams flew in, isolated the sick, and donned protective gear to treat them and bury the dead.

    2
    A volunteer receiving the experimental Ebola vaccine at a clinic in Conakry, Guinea, in 2015. Credit Yann Libessart/Medicins Sans Frontieres, via European Pressphoto Agency

    But that tactic failed in 2014 when the virus reached crowded capital cities, where it spread like wildfire and dead bodies piled up in the streets.

    The new vaccine has some flaws, experts said. It appears to work only against one of the two most common strains of the Ebola virus, and it may not give long-lasting protection. Some of those who get it report side effects like joint pain and headaches.

    “It’s certainly good news with regard to any new outbreak — and one will occur somewhere,” said Dr. Anthony S. Fauci, director of the National Institute for Allergy and Infectious Diseases, which makes many vaccines and did some early testing on this one. “But we still need to continue working on Ebola vaccines.”

    The Lancet study was done in 11,841 residents of Guinea last year. Among the 5,837 people who got the vaccine, none came down with Ebola 10 or more days later. There were 23 Ebola cases among the thousands of others not immediately vaccinated.

    (The 10-day window was important because the trial used the “ring vaccination” technique developed during the drive to eliminate smallpox. Once a confirmed case was found, researchers contacted everyone in the circle of family, friends, neighbors and caregivers around the victim. About half the “circles” were offered vaccine. No one who fell ill within the first nine days after vaccination was counted, however, because it was assumed that they had already been infected before vaccination.)

    The Ebola trial was led by the World Health Organization, the Guinean Health Ministry, Norway’s Institute of Public Health and other institutions. The vaccine, known as rVSV-ZEBOV, was developed over a decade ago by the Public Health Agency of Canada and the United States Army and is now licensed to Merck.

    Its genetic “spine” is that of a vesicular stomatitis virus, which sickens cattle but usually does not infect humans. Spliced into the spine is the gene coding for an Ebola virus surface protein that prompts the immune system to make antibodies.

    Tests in monkeys showed that one shot protected all of them when it was given at least a week before they were given a high dose of Ebola. The shot even protected a few monkeys who received it a day after being infected with Ebola.

    The Ebola virus has five known subtypes, the most common of which are Ebola-Zaire, the one that caused the West African outbreak, and Ebola-Sudan. Ebola is also related to Marburg virus, which is similarly lethal.

    An ideal vaccine would protect against all Ebola strains and Marburg. However, Dr. Kieny said, it may not be possible to make a shot effective against several strains if it is t based on the VSV spine because VSV triggers a lot of side effects.

    Risks that are acceptable in the midst of a deadly epidemic are not acceptable in a preventive vaccine given to healthy children and adults, several experts noted.

    The new vaccine is “a step in the right direction but not the ultimate solution,” said Dr. Gary J. Nabel, chief scientific officer for global health research at the Sanofi pharmaceutical company, who designed a different Ebola vaccine in the 1990s when he worked at the National Institutes of Health.

    A randomized clinical trial involving tens of thousands of subjects is the preferred way to test any vaccine, he noted. But by the time testing could start in mid-2015 in West Africa, isolation and treatment of the sick in tent hospitals had made Ebola cases so rare that researchers had to switch to ring vaccination around the few they could find.

    A likely candidate for a routine Ebola vaccine is one now being developed by GSK, Dr. Nabel said. It uses two shots: the first has the Ebola surface protein attached to a chimpanzee adenovirus that can infect humans without harming them; the second uses a weakened pox virus similar to that used in smallpox vaccine.

    Dr. Seth F. Berkley, chief executive of Gavi, the Vaccine Alliance, said his organization’s board voted in late 2014 to spend up to $390 million for 12 million doses of an Ebola vaccine. At the time, several companies had candidates but none had been fully tested in humans. “That was at a time when the epidemic was raging and we did not know if it could be controlled without a vaccine,” he said.

    By early last year, when preliminary results suggested the Merck vaccine worked well, Gavi gave the company $5 million to make 300,000 doses as an emergency supply to be used if Ebola-Zaire exploded again.

    It is not yet clear how big a stockpile will eventually be created. Merck is now required to seek approval of its vaccine from the World Health Organization, which itself requires licensing by a major regulatory agency like the United States Food and Drug Administration or the European Medicines Agency.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

     
  • richardmitnick 9:57 am on September 9, 2016 Permalink | Reply
    Tags: , , EBOLA, , , ,   

    From Vanderbilt: “Investigators create ‘Trojan Horse’ to fight Ebola” 

    Vanderbilt U Bloc

    Vanderbilt University

    Sep. 8, 2016
    Bill Snyder
    william.snyder@Vanderbilt.Edu
    (615) 322-4747

    A multi-center research team including scientists from the Vanderbilt Vaccine Center has come up with a clever “Trojan Horse” strategy for thwarting the highly lethal Ebola virus.

    Using “bispecific” antibodies — two monoclonal antibodies combined into a single package — they first tricked the virus into revealing a normally hidden binding site required for infection. Then in a mouse model, they blocked the site, fully protecting the animals from Ebola infection.

    Their findings, reported in this week’s Science magazine, suggest that this two-step, “deliver-and-block” strategy can provide broad protection against Ebola and other members of its hemorrhagic filovirus family, including the Marburg virus.

    We were intrigued to find this remarkable antibody that has the capacity to inhibit both Marburg and Ebola viruses,” said James Crowe Jr., M.D., Ann Scott Carell Professor in the Vanderbilt University School of Medicine and director of the Vanderbilt Vaccine Center at Vanderbilt University Medical Center.

    “The team’s feat of delivering the antibody into cells using creative engineering tricks so that it can kill Ebola inside cells is very exciting,” Crowe said.

    This advance is only the latest in a string of fundamental discoveries made during the past decade by a far-flung group of researchers including Crowe and four other corresponding authors of the paper.

    The four are Kartik Chandran, Ph.D., and Jonathan Lai, Ph.D., of Albert Einstein College of Medicine in New York, John Dye, Ph.D., of the U.S. Army Medical Research Institute of Infectious Diseases in Fort Detrick, Maryland, and Javad Aman, Ph.D., of Integrated Biotherapeutics in Gaithersburg, Maryland.

    Like other viruses, Ebola must “hijack” factors in the cells it infects to make copies of itself. As a first step, the virus enters a vesicle called an endosome inside the cell. There it commandeers two cellular enzymes called proteases to cut a sugar-bearing glycoprotein on its surface in two.

    Cleavage of the glycoprotein reveals a previously hidden receptor-binding site that attaches to another cellular factor, a cholesterol transporter protein called Niemann–Pick C1 or NPC1. This step is essential for infection to occur.

    Mutations in the NPC1 gene result in an abnormal protein that causes the rare lipid storage disorder Niemann-Pick type C disease. While patients with this disease are often quite ill, their abnormal NPC1 protein also renders them resistant to infection by Ebola and the related Marburg virus.

    Last year, Crowe, Vanderbilt graduate student Andrew Flyak and colleagues at The Scripps Research Institute in La Jolla, California, reported that a human survivor of a severe Marburg infection had neutralizing antibodies that recognized and blocked the NPC1 binding site in Marburg virus

    These antibodies also could bind to the Ebola virus, but only to the form of the virus inside cells.

    Crowe and Flyak followed up that finding by generating a “monoclonal” antibody, called MR72, which specifically recognized and could block the NPC1 binding site. To actually prevent Ebola virus infection, however, they’d have to get the antibody into the endosome inside the cell where the action is taking place.

    To do that, the researchers fused MR72 to another antibody, called FVM09, which recognizes and attaches to the Ebola glycoprotein before it is cut in two. The result was an immunological “Trojan horse.” Once the virus brought its antibody cargo into the endosome, MR72 went to work, and blocked infection.

    “This Trojan horse bispecific antibody approach may also find utility against other viral pathogens known to use intracellular receptors,” they concluded.

    Other contributors to the current study were Erica Ollmann Saphire, Ph.D., at Scripps and Zachary Bornholdt, Ph.D., now at Mapp Pharmaceutical in San Diego. The study was supported in part by National Institutes of Health grants AI109762, AI088027 and AI122403.

    See the full article here .

    You can Help Stamp Out EBOLA.

    This WCG project runs at Scripps Institute

    Outsmart Ebola Together

    Visit World Community Grid (WCG). Download and install the BOINC software on which it runs. Attach to the Outsmart Ebola Together project. This will allow WCG to use your computer’s free CPU cycles to process computational data for the project.

    WCGLarge
    WCG Logo New

    BOINCLarge
    BOINC WallPaper

    While you are at WCG and BOINC, check out the other very worthwhile projects running on this software. All project results are “open source”, free for the use of scientists world while to advance health and other issues of mankind.

    MyBOINC

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Vanderbilt Campus

     
  • richardmitnick 3:25 pm on August 12, 2016 Permalink | Reply
    Tags: , EBOLA, , ,   

    From Scripps: “Team Pinpoints Ebola’s Weak Spots” 

    Scripps
    Scripps Research Institute

    8.12.16
    Madeline McCurry-Schmidt

    Scientists at The Scripps Research Institute (TSRI) now have a high-resolution view of exactly how the experimental therapy ZMapp™ targets Ebola virus.

    The new study is also the first to show how an antibody in the ZMapp™ “drug cocktail” targets a second Ebola virus protein, called sGP, whose vulnerable spots had previously been unknown.

    “This sGP protein is tremendously important,” said TSRI Professor Erica Ollmann Saphire, who co-led the study with TSRI Associate Professor Andrew Ward. “This is the roadmap we need to target the right molecules in infection.”

    “Determining the proper balance in targeting these two Ebola proteins will be key to building improved therapeutics,” added Ward.

    The study was published August 8, 2016 in the journal Nature Microbiology.

    1
    The team succeeded in showing how experimental therapy ZMapp™ targets the Ebola virus, here pictured targeting the virus’s GP protein. (Image courtesy of Andrew Ward and Jesper Pallesen.)

    Zooming in on ZMapp™

    Scientists need detailed images of Ebola virus’s molecular structure. Like enemy reconnaissance, structures can show where Ebola is vulnerable and how medical treatments can neutralize it.

    TSRI scientists are harnessing an imaging technique called cryo-electron microscopy (in which a sample is pelted with electrons) to create high-resolution, 3-D images of Ebola virus and the antibodies that fight it.

    “We’re at the cutting edge of our ability to resolve high-resolution protein complexes,” said TSRI Research Associate C. Daniel Murin, co-first author of the new study with TSRI Research Associate Jesper Pallesen.

    In the new study, the researchers used cryo-electron microscopy to see exactly how Ebola virus interacts with the three antibodies in the ZMapp™ experimental therapy produced by Mapp Biopharmaceutical, also a study collaborator.

    The researchers had imaged these interactions at a low resolution in a 2014 study, but the new study revealed substantially more details, including the exact angles the antibodies use to approach the molecule on the surface of the virus, termed its surface glycoprotein (GP), and the individual amino acid contact points at which the antibodies bind GP. This information provides new clues to researchers trying to make the antibodies even more effective.

    “The three components of ZMapp™, now resolved at high-resolution, can be further engineered in a structure-based manner for improved potency,” said Ward.

    Solving an Elusive Structure

    Next, the researchers took a closer look at one of the three antibodies that make up ZMapp™, called 13C6. This antibody is unique because it can also target the soluble Ebola protein sGP.

    sGP’s role in infection is a mystery. Ebola virus makes the protein profusely, indicating that it is important, but then sGP appears just to float in a person’s blood serum. One theory is that sGP may be essential in the natural host “reservoir.”

    “Eighty to ninety percent of what Ebola virus makes in infection is this shed molecule,” said Saphire. “It’s like a smoke screen, and we need to know where it is similar to our target GP and where it is different.”

    To add to the mystery, Ebola makes GP and sGP using the same gene. A small difference in the way the gene is read changes how the molecules are shaped and changes their roles.

    One obstacle to understanding sGP is that it is too small to be seen with cryo-electron microscopes. To solve this problem, the researchers added “bulk” by pairing sGP with antibodies, including 13C6. This allowed them to kill two birds with one stone—they could see sGP’s structure while also studying how antibodies interact with it.

    The new image shows the binding sites, or “epitopes,” the antibody targets. “We can see hot spots on this virus that we can hit,” said Pallesen.

    This study is the latest research from the Viral Hemorrhagic Fever Consortium, an international partnership of research institutes led by Saphire. The researchers said collaboration with the consortium was key to this study, allowing scientists to share samples and data, including viral genetic sequences isolated from patients in the most recent Ebola outbreak.

    In addition to Saphire, Ward, Murin and Pallesen, authors of the study, Structures of Ebola virus GP and sGP in complex with therapeutic antibodies, were Natalia de Val, Christopher A. Cottrell, Kathryn M. Hastie, Hannah Turner and Marnie Fusco of TSRI; Kristian G. Andersen of TSRI and the Scripps Translational Science Institute; Andrew I. Flyak and James E. Crowe of Vanderbilt University and Larry Zeitlin of Mapp Biopharmaceutical.

    This study was supported by the National Institutes of Health (NIH, grant R01 AI067927), the NIH’s National Institute of Allergy and Infectious Diseases (grants U19AI109762 and U19AI109711) and the National Science Foundation.

    See the full article here .

    You can Help Stamp Out EBOLA.

    This WCG project rubs at Scripps Institute

    Outsmart Ebola Together

    You can help researchers at The Scripps Research Institute find a cure for Ebola by donating your computing power to this project and encouraging others to join.

    Visit World Community Grid (WCG). Download and install the BOINC software on which it runs. Attach to the Outsmart Ebola Together project. This will allow WCG to use your computer’s free CPU cycles to process computational data for the project.

    WCGLarge
    WCG Logo New

    BOINCLarge
    BOINC WallPaper

    While you are at WCG and BOINC, check out the other very worthwhile projects running on this software. All project results are “open source”, free for the use of scientists world while to advance health and other issues of mankind.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    The Scripps Research Institute (TSRI), one of the world’s largest, private, non-profit research organizations, stands at the forefront of basic biomedical science, a vital segment of medical research that seeks to comprehend the most fundamental processes of life. Over the last decades, the institute has established a lengthy track record of major contributions to the betterment of health and the human condition.

    The institute — which is located on campuses in La Jolla, California, and Jupiter, Florida — has become internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases, virology, and synthetic vaccine development. Particularly significant is the institute’s study of the basic structure and design of biological molecules; in this arena TSRI is among a handful of the world’s leading centers.

    The institute’s educational programs are also first rate. TSRI’s Graduate Program is consistently ranked among the best in the nation in its fields of biology and chemistry.

     
  • richardmitnick 9:13 am on March 22, 2016 Permalink | Reply
    Tags: , EBOLA, ,   

    From “Outsmart Ebola Together” at WCG 

    New WCG Logo
    WCGLarge

    21 Mar 2016
    Dr. Erica Ollmann Saphire, PhD
    The Scripps Research Institute

    Summary
    In this project update, Dr. Erica Ollman Sapphire covers many fronts on the fight against Ebola, from the long-term effects of the disease on survivors, to her team’s continued experiments using World Community Grid and their work with other Ebola researchers.

    The Long-Term Effects of the Ebola Epidemic

    As the bulk of the Ebola virus epidemic winds down, we see long-term effects of the infection in survivors. For some, the virus has entered the central nervous system, causing re-emergence of meningitis-like disease, severe eye pain, loss of vision and other complications. Evidence of the virus has been isolated from the semen of survivors up to nine months after release from treatment centers. This has likely resulted in at least one case of sexually transmitted Ebola virus. Additional cases of Ebola virus have erupted in Sierra Leone and in Liberia after each country was declared free of human-to-human transmission. Appearance of these new cases means that the virus is likely still in the ecological reservoir or is being re-introduced into the environment or to other humans. At the same time, survivors face numerous health challenges, economic challenges, personal losses and social stigmas.

    Searching for Effective Treatments

    The need for small molecule drugs that can treat Ebola virus infection remains. Small molecules that could cross the blood-brain barrier could be used to treat the life-threatening cases in which the virus expanded in the central nervous system long after release from the clinic. Importantly, such molecules must not only be developed against Ebola virus but against similar viruses that could cause the next outbreak.

    The goal of Outsmart Ebola Together is to identify candidate drugs active against Ebola virus, Lassa virus and other related health threats. To accomplish this goal, we are studying the atomic structure of the target, which is the Ebola virus molecule, and the ligands, which are the structures of millions of candidate drug molecules. The target and ligand are evaluated against one another, and a software program computes the tendency of the molecules to associate with each other. Simulating these experiments on computers saves considerable time and cost, because laboratory testing requires purchasing or synthesizing the candidate molecules, a potentially time-consuming and expensive process.

    So far, 33.4 million of these virtual experiments have been conducted by World Community Grid volunteers, the percentage of tasks completed is increasing, and will probably reach 100% soon. We are currently seeking a computational scientist (and funding to support him or her) to filter this tremendous body of work into the most meaningful compounds we can test in a laboratory.

    Recent Publications and Continuing Work

    In the meantime, new targets are planned. Recently, we solved the structures of the protein of Marburg virus that builds and releases new viruses from the infected cell, while simultaneously silencing the ability of our cells to detect and fight the infection (Oda, et al. Journal of Virology, Crystal structure of Marburg virus VP40: matrix assembly and immunosuppression). In that effort, we are working with an excellent team of biophysicists at Notre Dame University, led by Dr. Robert Stahelin, to understand how the virus interacts with and hijacks the membranes of our cells. Understanding the structure of the Marburg virus is important because, like the Ebola virus, it can cause fever, severe bleeding, organ failure, and, in many cases, death.

    Our structure of the molecule that achieves the same functions for Lassa virus–which can also cause severe bleeding, fever, and death–will be released soon (Hastie, et al. in press).

    A collaborative team involving my lab has searched in the blood of a survivor of this Ebola outbreak to find some of the highest potency antibodies yet identified (Bornholdt, et al. 2016 Science, Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak). This group is part of the global consortium that gathers and analyze antibodies against these deadly viruses, and we were recently featured on the show Breakthrough by National Geographic.

    We thank all World Community Grid volunteers who have donated computing power to Outsmart Ebola Together, and we are grateful for your continued support as the project progresses.

    See the full article here.

    Please help promote STEM in your local schools.
    STEM Icon

    Stem Education Coalition

    World Community Grid (WCG) brings people together from across the globe to create the largest non-profit computing grid benefiting humanity. It does this by pooling surplus computer processing power. We believe that innovation combined with visionary scientific research and large-scale volunteerism can help make the planet smarter. Our success depends on like-minded individuals – like you.”

    WCG projects run on BOINC software from UC Berkeley.

    BOINC is a leader in the field(s) of Distributed Computing, Grid Computing and Citizen Cyberscience.BOINC is more properly the Berkeley Open Infrastructure for Network Computing.

    BOINC WallPaper

    CAN ONE PERSON MAKE A DIFFERENCE? YOU BET!!

    “Download and install secure, free software that captures your computer’s spare power when it is on, but idle. You will then be a World Community Grid volunteer. It’s that simple!” You can download the software at either WCG or BOINC.

    Please visit the project pages-
    Outsmart Ebola together

    Outsmart Ebola Together

    Mapping Cancer Markers
    mappingcancermarkers2

    Uncovering Genome Mysteries
    Uncovering Genome Mysteries

    Say No to Schistosoma

    GO Fight Against Malaria

    Drug Search for Leishmaniasis

    Computing for Clean Water

    The Clean Energy Project

    Discovering Dengue Drugs – Together

    Help Cure Muscular Dystrophy

    Help Fight Childhood Cancer

    Help Conquer Cancer

    Human Proteome Folding

    FightAIDS@Home

    World Community Grid is a social initiative of IBM Corporation
    IBM Corporation
    ibm

    IBM – Smarter Planet
    sp

     
  • richardmitnick 10:21 am on March 15, 2016 Permalink | Reply
    Tags: , EBOLA, ,   

    From SLAC: “X-ray Studies at SLAC and Berkeley Lab Aid Search for Ebola Cure” 


    SLAC Lab

    March 14, 2016
    No writer credit

    Research Reveals Structures That Could Be Key to Preventing Infection

    q
    TPC1 channel that Ebola and related filoviruses use to infect cells.

    In experiments carried out partly at the Department of Energy’s SLAC National Accelerator Laboratory, scientists have determined in atomic detail how a potential drug molecule fits into and blocks a channel in cell membranes that Ebola and related filoviruses need to infect victims’ cells.

    The study by researchers at University of California, San Francisco marks an important step toward finding a cure for Ebola and other diseases that depend on the channel. The results were published March 9 in Nature.

    “There are no effective treatments for filovirus infections in humans,” said UCSF postdoctoral researcher Alex Kintzer, who performed the study with Professor Robert Stroud. “With these new structures, pharmaceutical chemists can now design new candidate drug molecules that would be more efficient and effective in blocking the channel and defeating these viruses.”

    To determine the structures, Kintzer first made crystals containing many copies of the target channel protein, called TPC1, bound to the potential drug molecule, Ned-19.

    The researchers then exposed the crystals to intense X-rays at two DOE Office of Science User Facilities – SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL) and the Advanced Light Source (ALS) at Lawrence Berkeley National Laboratory.

    SLAC SSRL
    SSRL at SLAC

    LBL ALS interior
    ALS at LBL

    Analyzing the patterns and intensities of the X-rays that diffract from the crystals enables researchers to determine their atomic structures.

    Isolating TPC1 from its complex membrane structure is a difficult process that often results in loosely packed crystals that produce faint diffraction patterns, and finding crystals that diffracted well enough to determine the atomic structure of TPC1 required extensive analysis. SSRL’s Beam Line 12-2 was crucial to the successful analysis of these crystals, because its bright X-rays are particularly well-suited for biomedical diffraction studies, and its pixel-array detector is 1,000 times faster than conventional detectors in logging data.

    “These features of Beam Line 12-2 were especially important in enabling Alex to rapidly analyze the diffraction of his challenging crystals,” said Ana Gonzalez, SSRL’s Macromolecular Crystallography User Support Group leader, who helped Kintzer take full advantage of the beamline’s capabilities.

    Even so, the project involved testing about 6,900 crystals during more than 36 sessions at SSRL and ALS. It took nearly four years to complete, from planning to publication.

    One interesting aspect of this study is that the specific TPC1 sample the researchers used did not come from a human or lab animal. Rather, it was from the cells of a weedy Eurasian annual plant related to broccoli (called mouse-ear cress, or Arabidopsis thaliana) that researchers have used as a model species for studying cell activities and genetics since the mid-1940s. (In 2000, for example, A. thaliana’s genome was the very first plant genome to be sequenced.)

    “It’s common in this field to use well-studied non-human components that have similar genetic sequences, structures and functional properties,” Kintzer said.

    Future research plans include determining the structure of human TPC1 and investigating other molecules that may treat or cure other diseases that exploit that channel’s function.

    “For example, TPC1 function also plays important roles in the progression of diabetes, obesity, fatty liver disease, heart disease and such neurodegenerative disorders as Parkinson’s disease,” Kintzer said. “We hope our work will eventually lead to more effective medicines for treating these diseases as well.”

    The research was supported by the National Institutes of Health (NIH) and the Sandler Foundation. Funding for the SSRL Structural Molecular Biology Program is provided by the DOE Office of Science and the NIH National Institute of General Medical Sciences (NIGMS). The Berkeley Center for Structural Biology is supported by NIGMS and the Howard Hughes Medical Institute.

    Citation: A. Kintzer and R. Stroud, Nature, 9 March 2016 (10.1038/nature17194).

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    SLAC Campus
    SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the DOE’s Office of Science.
    i1

     
  • richardmitnick 11:30 am on January 16, 2016 Permalink | Reply
    Tags: , EBOLA, , ,   

    From Nature: “Ebola re-emerges in Sierra Leone” 

    Nature Mag
    Nature

    15 January 2016
    Richard Van Noorden

    Temp 1
    A treatment facility in the Lunsar Ebola Treatment Centre in Port Loko, Sierra Leone. Pete Muller/National Geographic Creative

    When the World Health Organization (WHO) declared on 14 January that the spread of Ebola had been halted in West Africa, it cautioned that cases of the virus might yet re-emerge. That is exactly what has happened in Sierra Leone, where another death from Ebola was announced hours after the WHO’s statement.

    Health officials told reporters that a 22-year-old woman had died in Magburaka after falling ill in Baomoi Luma, near the border of Guinea. A test for Ebola was confirmed positive only after her death, which occurred earlier in the week, raising concerns that she may have been in contact with others while contagious.

    The case is Sierra Leone’s first since it was declared free of Ebola on 7 November 2015, although the country was still in a 90-day period of enhanced surveillance. The WHO and local partners say that they are investigating its origin and identifying the woman’s contacts.

    Flare-ups expected

    Although the epidemic phase of Ebola seems to be over, isolated cases were expected. The WHO considers human transmission of the virus to have halted when a country has gone 42 days (twice the virus’s incubation period) with no new cases — but the virus can persist in survivors for months in semen, as well as in tissues such as the eye, the central nervous system, the prostate gland and the placenta. It also remains hidden in animal reservoirs.

    Liberia, for example, was pronounced Ebola-free in May 2015, but the virus flared up twice before the WHO could declare the country clear of the virus again on 14 January. “We are now at a critical period in the Ebola epidemic as we move from managing cases and patients to managing the residual risk of new infections,” Bruce Aylward, special representative for the WHO’s Ebola response, noted in the organization’s press-released statement at the time.

    There is a particular focus on the potential of sexual transmission of Ebola to cause occasional cases. After a first-known case of sexual transmission of the disease was confirmed in Liberia last October, Armand Sprecher, a public-health specialist with Médecins Sans Frontières (also known as Doctors without Borders) in Brussels, wrote in an editorial: “The challenge with sexual transmission is not that it would be a source of many new Ebola virus disease cases, but that it may be a source of late cases.”

    Nature doi:10.1038/nature.2016.19180

    See the full article here .

    Want to help in the fight against Ebola? You can help from the comfort of your home by contributing unused CPU cycles of your personal computer (Windows, Mac, Linux) to World Community Grid’s (WCG) Outsmart Ebola Together project. Join WCG, attach to the project, let your computer do the data computation.

    WCGLarge
    WCG new
    Outsmart Ebola Together

    WCG runs on BOINC software from UC Berkeley.

    BOINC WallPaper

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Nature is a weekly international journal publishing the finest peer-reviewed research in all fields of science and technology on the basis of its originality, importance, interdisciplinary interest, timeliness, accessibility, elegance and surprising conclusions. Nature also provides rapid, authoritative, insightful and arresting news and interpretation of topical and coming trends affecting science, scientists and the wider public.

     
  • richardmitnick 11:23 am on December 24, 2015 Permalink | Reply
    Tags: , , EBOLA, ,   

    From U Colorado: “CU-Boulder study reveals evolutionary arms race between Ebola virus, bats” 

    U Colorado

    University of Colorado Boulder.

    December 22, 2015
    Sara Sawyer, 303-735-0531
    ssawyer@colorado.edu

    Trent Knoss, CU-Boulder media relations, 303-735-0528
    trent.knoss@colorado.edu

    Temp 1
    The Ebola virus, isolated in November 2014 from patient blood samples obtained in Mali. The virus was isolated on Vero cells in a BSL-4 suite at Rocky Mountain Laboratories. Credit: NIAID

    The Ebola virus and fruit bats have been waging a molecular battle for survival that may have started at least 25 million years ago, according to a study led by researchers at the University of Colorado Boulder, Albert Einstein College of Medicine and the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID).

    The findings, published today in the journaleLife [no link], shed new light on the biological factors that determine which bat species may harbor the virus in between outbreaks in humans and how bats may transmit the virus to people.

    The researchers showed that a single amino acid change in the Ebola virus could overcome the resistance of the African straw-colored fruit bat cells to infection. These findings hint at one way in which Ebola and other highly infectious filoviruses can evolve to better infect a host.

    “There seems to be a low barrier for Ebola virus to establish itself in this type of bat,” said co-lead author Sara Sawyer, an associate professor in CU-Boulder’s Molecular, Cellular, and Developmental Biology and the BioFrontiers Institute. “One has to wonder why that has not happened yet.”

    To learn more, the researchers exposed cells from four types of African bats (two of them previously linked to Ebola) to several filoviruses, including Ebola. Cells from only one type of bat proved resistant to Ebola virus infection: the African straw-colored fruit bat, which is commonly hunted for bushmeat in West Africa and migrates long distances.

    Outbreaks of Ebola virus disease among humans are thought to begin when a person comes into contact with a wild animal carrying Ebola virus.

    “We knew from our previous research that Ebola virus infects host cells by attaching its surface glycoprotein to a host cell receptor called NPC1,” said Kartik Chandran, an associate professor of microbiology and immunology at Albert Einstein College of Medicine in New York and a co-lead author of the study. “Here, we show how bats have evolved to resist Ebola infection and how, in turn, the virus could have evolved to overcome that resistance.”

    “Identifying potential animal reservoir hosts for Ebola virus will provide a crucial guide for public health prevention and response programs going forward,” said Maryska Kaczmarek, a graduate researcher in Sawyer’s lab at CU-Boulder and a co-author of the study.

    There are currently no FDA-approved treatments or vaccines for the Ebola virus. The 2014 Ebola outbreak in West Africa was the world’s deadliest to date, infecting an estimated 28,000 people and killing more than 11,000, according to the Centers for Disease Control and Prevention.

    The study was co-authored by Melinda Ng, Esther Ndungo, Rohit Jangra and Rohan Biswas, all at Albert Einstein; John Hawkins and Ann Demogines, all at University of Texas at Austin; Andrew Herbert, Ana Kuehne and Rebekah James, all at USAMRIID; Tabea Binger and Marcel Müller at University of Bonn Medical Center; Robert Gifford at University of Glasgow; Meng Yu and Lin-Fa Wang at Duke-NUS Graduate Medical School; Thijn Brummelkamp at Netherlands Cancer Institute; Christian Drosten at the German Centre for Infectious Diseases Research; and Jens Kuhn at the National Institutes of Health’s Integrated Research Facility at Fort Detrick.

    This research was supported by grants from National Institutes of Health, the Defense Threat Reduction Agency, European Union FP-7 Antigone, the EBOKON Project, and the National Research Foundation Singapore.

    See the full article here .

    If you want to help in the fight against Ebola, join World Community Grid [WCG]and attach to the Outsmart Ebola Together project running at the Scripps Institute. WCG runs on BOINC software from UC Berkeley.

    WCGLarge

    Outsmart Ebola Together

    Scripps

    BOINC WallPaper

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    U Colorado Campus

    As the flagship university of the state of Colorado, CU-Boulder is a dynamic community of scholars and learners situated on one of the most spectacular college campuses in the country. As one of 34 U.S. public institutions belonging to the prestigious Association of American Universities (AAU) – and the only member in the Rocky Mountain region – we have a proud tradition of academic excellence, with five Nobel laureates and more than 50 members of prestigious academic academies.

    CU-Boulder has blossomed in size and quality since we opened our doors in 1877 – attracting superb faculty, staff, and students and building strong programs in the sciences, engineering, business, law, arts, humanities, education, music, and many other disciplines.

    Today, with our sights set on becoming the standard for the great comprehensive public research universities of the new century, we strive to serve the people of Colorado and to engage with the world through excellence in our teaching, research, creative work, and service.

     
  • richardmitnick 3:46 pm on October 6, 2015 Permalink | Reply
    Tags: , EBOLA, , ,   

    From Outsmart Ebola Together at WCG: “Finding new avenues to attack Ebola” 

    New WCG Logo

    6 Oct 2015
    Dr. Erica Ollmann Saphire, PhD, The Scripps Research Institute

    Summary
    Efforts to simulate matches between candidate compounds and one key Ebola virus protein are largely complete. Simulations of matches against another, newly discovered target protein are beginning now. Even as simulation work continues, the team is beginning to analyze these results and home in on compounds that could form the basis for effective new drugs against Ebola and other related diseases. Thanks to your help, and a new grant, the work is proceeding well.

    1
    Two Protein Data Bank structures for the ribonuclease H domain of HIV reverse transcriptase. We used structural and experimental data for this domain to optimize our analysis protocols for the Lassa NP exonuclease site.

    Thanks to the efforts of thousands of World Community Grid members, my team has continued to make progress on Outsmart Ebola Together, a project whose goal is to find new drugs for curing Ebola and related life-threatening viral hemorrhagic fevers.

    Outsmart Ebola Together began with a study of potential drug attacks against the receptor-binding site of the Ebola surface glycoprotein (GP). We then announced the start of work on a second drug target: the nucleoprotein (NP) of Lassa Fever virus. Specifically, we are looking for drugs that attack the newly discovered “exonuclease site” of Lassa NP. This exonuclease site helps conceal the virus’s presence from the infected human cell by destroying the virus’s own excess production of double-stranded RNA.

    We have since prepared research tasks for testing the Lassa NP exonuclease site against millions of potential drugs. These tasks are now ready for use, and will be sent out to World Community Grid volunteers over the coming months.

    Our lab has also been investigating the Ebola NP and VP35 proteins. NP and VP35 must engage in a series of specific interactions with each other as Ebola virus replicates. These newly discovered interactions could potentially be disrupted by new drugs, making NP and VP35 possible future targets for investigation by Outsmart Ebola Together.

    At this stage in the project, we’ve gathered enough data that we need to begin focusing on analysis procedures for the data already returned by World Community Grid volunteers. We must analyze the data for both the Ebola GP receptor-binding site and the Lassa NP exonuclease site; and our analysis procedures must be sufficient to filter out false positives from the large quantity of results returned.

    For each viral protein site that we test against potential drugs, we assure the validity of our analysis as follows: We select a substantially analogous site (generally from a different virus) for which there exists experimental data about potential drugs that bind or do not bind to the site. We then tune our analysis protocols so that, when applied to this site, our analysis results closely match the known experimental results. Only when this is done do we feel that we can confidently apply the same analysis protocols to the site of current interest.

    In particular, this summer we looked closely at analysis optimization for the Lassa NP exonuclease site. As the analogous well-studied site, we chose the “ribonuclease H domain” of HIV reverse transcriptase, which has strong similarities to the Lassa NP exonuclease site in its protein structure and use of catalytic metal ions. The optimization of our analysis protocols against experimental data for the HIV ribonuclease H domain is now complete, and we are looking forward to the arrival of the Lassa NP exonuclease data as it is processed by World Community Grid volunteers. Candidate drugs that pass the analysis stage will go on to a next round of experiments, conducted in the lab rather than by computer simulation.

    We are also happy to announce that a $50,000 grant to support this work has been provided by the Robert Wood Johnson Foundation President’s Grant Fund of the Princeton Area Community Foundation. With this grant and the vast computing resources of World Community Grid, our way to the successful completion of the project is clear.

    As always, we close with a thank-you to the volunteers who have run this work for us. As you can see, we’ve already made significant progress but there is much work still to do. Make sure you’re signed up to contribute to this project, and spread the word about our lifesaving work!

    See the full article here.

    Please help promote STEM in your local schools.
    STEM Icon

    Stem Education Coalition

    World Community Grid (WCG) brings people together from across the globe to create the largest non-profit computing grid benefiting humanity. It does this by pooling surplus computer processing power. We believe that innovation combined with visionary scientific research and large-scale volunteerism can help make the planet smarter. Our success depends on like-minded individuals – like you.”

    WCG projects run on BOINC software from UC Berkeley.

    BOINC is a leader in the field(s) of Distributed Computing, Grid Computing and Citizen Cyberscience.BOINC is more properly the Berkeley Open Infrastructure for Network Computing.

    BOINC WallPaper

    CAN ONE PERSON MAKE A DIFFERENCE? YOU BET!

    “Download and install secure, free software that captures your computer’s spare power when it is on, but idle. You will then be a World Community Grid volunteer. It’s that simple!” You can download the software at either WCG or BOINC.

    Please visit the project pages-
    Outsmart Ebola together

    Outsmart Ebola Together

    Mapping Cancer Markers
    mappingcancermarkers2

    Uncovering Genome Mysteries
    Uncovering Genome Mysteries

    Say No to Schistosoma

    GO Fight Against Malaria

    Drug Search for Leishmaniasis

    Computing for Clean Water

    The Clean Energy Project

    Discovering Dengue Drugs – Together

    Help Cure Muscular Dystrophy

    Help Fight Childhood Cancer

    Help Conquer Cancer

    Human Proteome Folding

    FightAIDS@Home

    World Community Grid is a social initiative of IBM Corporation
    IBM Corporation
    ibm

    IBM – Smarter Planet
    sp

     
  • richardmitnick 11:15 am on October 3, 2015 Permalink | Reply
    Tags: , EBOLA, ,   

    From Oxford: “Behind the scenes of creating the ground-breaking Ebola vaccine” 

    U Oxford bloc

    Oxford University

    Professor Adrian Hill of Oxford’s Jenner Institute led the first clinical trial of a successful Ebola virus vaccine last year. To target the outbreak his remarkable team compressed a process that takes six months into six weeks.

    1

    The recent Ebola outbreak was the deadliest since the virus’ discovery in the 1970s. Fortunately Professor Adrian Hill, Director of Oxford’s Jenner Institute, and his team managed to create a vaccine response in record time.

    At his Alumni Weekend talk, Professor Hill described the desperate situation that West Africa was in last year. Ebola was in the news every day, with death tolls spiralling up through the summer. There were no vaccines known to protect against Ebola, or drugs to treat those infected at the time. Promising vaccine candidates did exist in the US, but only one had been tested in humans and had been subsequently abandoned.

    Usually Ebola outbreaks have been contained using the traditional methods of containment in Central Africa, but it was spreading through the continent rapidly – in Guinea, Sierra Leone, and Liberia – in 2014. With no vaccines ready to be tested out in West Africa the situation was grave, Professor Hill explained.

    2

    The resulting ambitious trial at Oxford was funded by the Wellcome Trust, Medical Research Council and Department for International Development. Phase one began in mid-September 2014 with 60 volunteers, and a further 80 out in Mali in October – after the team was swamped with volunteers anxious to help.

    For the successful vaccine Professor Hill’s team used a single Ebola gene in a chimpanzee adenovirus to generate an immune response. As it did not contain any infectious virus material, it did not cause the patient to become infected. The trial’s efficiency exceeded all expectations, with a novel vaccine ready from the trial to finished product in nine months.

    3

    The researchers then used an innovative trial design in West Africa, in which the family, friends and contacts in a ‘ring’ around an Ebola patient would be given the vaccine. In March 2015, the first infected individuals were identified and the ring vaccination began in Guinea, which continues to have the majority of cases. Both this ‘ring’ approach and the vaccine were a great success.

    Looking to the future, Professor Hill reflected that it would be wonderful if Britain could manufacture vaccines ‘on a significant scale’ once again. David Cameron has promised £20million to protect Britain from future pandemics this year, but how that money will be allocated has not yet been decided.

    Professor Hill explained more broadly the challenges left facing vaccination development. On the positive side, only two countries in the world are left with polio, and smallpox has been eradicated. This leaves the big three vaccinations to find as HIV/AIDS, malaria, and an improved TB jab.

    In terms of Ebola itself, the vaccine that Professor Hill’s team worked on was for the Zaire strain, but there still remains to be one for the Sudan strain. He pointed out that there will ‘almost certainly’ be more major outbreaks, especially as Africa’s population increases, people travel more and cities expand.

    For all of the team’s hard work, the University decided that their contributions should be recognised, and commissioned a University of Oxford Ebola medal this summer. The medals were presented by the Vice-Chancellor, Professor Andrew Hamilton, and the head of the Nuffield Department of Clinical Medicine, Professor Peter Ratcliffe. Professor Hamilton reflected: ‘The work of the team was absolutely critical. These kinds of outbreaks can arise at any time and we need to be ready to respond. They responded magnificently.’

    For further details about the Jenner Institute click here.

    Photographs courtesy of Oxford University Images

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    U Oxford campus

    Oxford is a collegiate university, consisting of the central University and colleges. The central University is composed of academic departments and research centres, administrative departments, libraries and museums. The 38 colleges are self-governing and financially independent institutions, which are related to the central University in a federal system. There are also six permanent private halls, which were founded by different Christian denominations and which still retain their Christian character.

    The different roles of the colleges and the University have evolved over time.

     
c
Compose new post
j
Next post/Next comment
k
Previous post/Previous comment
r
Reply
e
Edit
o
Show/Hide comments
t
Go to top
l
Go to login
h
Show/Hide help
shift + esc
Cancel