DOE News
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    The DOE Science News Source is a Newswise initiative to promote research news from the Office of Science of the DOE to the public and news media.
    • 2018-12-03 11:05:09
    • Article ID: 704778

    To curb maternal deaths in developing countries, researchers use X-rays to map a lifesaving drug in action

    New research will help in the quest to design low-cost drugs that can tackle postpartum bleeding and other conditions without severe side effects.

    • Credit: Yekaterina Kadyshevskaya/University of Southern California

      Using SLAC’s Linac Coherent Light Source, researchers mapped the shape of the EP3 receptor, one of the main triggers of labor in pregnant women. It’s shown here as tangles of teal coils; misoprostol, a drug known to stop postpartum bleeding in pregnant women, is shown as a yellow and red molecule that has bound into a pocket within the receptor.

    Every year, hundreds of thousands of women die during childbirth or due to pregnancy-related complications. Postpartum hemorrhaging, a condition in which the body bleeds excessively following the birth of a baby, is the leading cause of maternal mortality.

    Misoprostol, a generic drug that induces labor and stops postpartum bleeding, has become a staple in developing countries – where 99 percent of these deaths occur – because it’s affordable and easy to store and administer. Due to its far-reaching applications in reproductive health, it’s listed as an essential medicine by the World Health Organization. But the drug also targets other tissues in the cardiovascular and central nervous systems and the gastrointestinal tract, bringing about serious side effects.

    A team that includes researchers from the Bridge Institute at the University of Southern California (USC) and the Department of Energy’s SLAC National Accelerator Laboratory used X-rays to map the shape of a receptor in the body as it binds with misoprostol. This research, published in Nature Chemical Biology, could help in the quest to design low-cost drugs that can tackle postpartum bleeding without affecting other tissues.

    “Misoprostol is a key drug for women’s health, especially in countries that lack access to medical resources and facilities, where it saves many mothers’ lives at childbirth,” says co-author Raymond Stevens, director of the Bridge Institute at the USC Michelson Center for Convergent Bioscience and a professor of chemistry and biological sciences at USC. “The development of newer therapeutics that are more selective with the tissues they target would be an impactful advancement in women’s health. This research improves our understanding of how the drug works and provides a starting point for new drug discoveries.”

    Molecular impersonation

    Misoprostol is part of a class of drugs that bind to prostaglandin receptors, which produce a variety of physical effects in the body when activated. Because these drugs are so similar to the natural compounds in the body that bind to these receptors, they can control these effects, which include labor, inflammation, pain and fever.

    “The human body is built of a few trillions of cells, and these cells have to talk to each other,” says co-author Alex Batyuk, a scientist at SLAC’s Linac Coherent Light Source (LCLS) X-ray laser. “The way they communicate is through these receptors, which sit in the cell membrane and transmit signals in and out of cells. About a third of the drugs on the market act on these kinds of receptors, mimicking the natural compounds that cells use to communicate with each other.”

    Misoprostol works by targeting a prostaglandin receptor called EP3, one of the main triggers of labor in pregnant women. But because it can bind to a number of other receptors in a variety of tissues, the drug can produce side effects ranging from diarrhea to fetal heart abnormalities, fetal death and uterine rupture.

    Roadmap for drug design

    The researchers used LCLS to build a map of EP3 as it binds to misoprostol. They bound misoprostol to EP3, then crystallized the pair and zapped it with an X-ray laser beam, using the patterns formed when the X-rays scattered off the crystal to reconstruct the shape and structure of the receptor binding to the drug.

    Until now, researchers were unable to determine the structure of EP3 and how drugs like misoprostol target and bind to it, a major roadblock in drug development. This research is the first to provide the 3D structure of a receptor in the prostaglandin family and might even extend beyond misoprostol into drugs used to treat other medical conditions controlled by prostaglandin receptors such as arteriosclerosis, the thickening and hardening of the artery walls.

    “Trying to design new drugs without understanding the structure of the receptors they bind to is like trying to build a car from the ground up with no blueprint,” says Martin Audet, a biochemist at USC. “In this research, we produced a chemical map of this receptor to understand how it binds. This could enable us to get even more data about its molecular mechanics – how it moves and interacts with drug molecules – which will help us fine-tune other potential drug compounds and predict how they will impact the body. It provides a path forward to a new generation of drugs with fewer side effects.”

    The research team also included scientists from Stanford University; Arizona State University; the GPCR Consortium in California; Domain Therapeutics in Canada; the iHuman Institute and the School of Life Science and Technology, both in China; and Moscow Institute of Physics and Technology in Russia.

    Key components of this research were carried out at LCLS and at Argonne National Laboratory’s Advanced Photon Source, both DOE Office of Science user facilities. This work was supported by the National Institutes of Health; the Canadian Institute of Health and Research; the Science and Technology Centers Program of the National Science Foundation through BioXFEL; the GPCR Consortium; and the Russian Science Foundation.


    SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, Calif., SLAC is operated by Stanford University for the U.S. Department of Energy's Office of Science. For more information, please visit slac.stanford.edu.

    SLAC National Accelerator Laboratory is supported by the Office of Science of the U.S. Department of Energy. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time.

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    Ice Formed by Contact Freezing: Pressure Matters, Not Just Temperature

    Distortion of water droplet surface may increase the likelihood of the droplet freezing.

    Future Loss of Arctic Sea-Ice Cover Could Contribute to the Substantial Decrease in California's Rainfall

    A new modeling framework helps understand the consequences of future sea-ice loss in the Arctic.

    Tangled magnetic fields power cosmic particle accelerators

    Magnetic field lines tangled like spaghetti in a bowl might be behind the most powerful particle accelerators in the universe. That's the result of a new computational study by researchers from the Department of Energy's SLAC National Accelerator Laboratory, which simulated particle emissions from distant active galaxies.

    Argonne scientists maximize the effectiveness of platinum in fuel cells

    In new research from the U.S. Department of Energy's Argonne National Laboratory and published in Science, scientists have identified a new catalyst that uses only about a quarter as much platinum as current technology by maximizing the effectiveness of the available platinum.

    Drawn into a Whirlpool: A New Way to Stop Dangerous Fast Electrons in a Fusion Device

    A new phenomena forms vortices that trap particles, impeding electron avalanches that harm fusion reactors.

    Barely scratching the surface: A new way to make robust membranes

    Argonne researchers have demonstrated a new technique's viability for membranes.

    During Droughts, Bacteria Help Sorghum Continue Growing

    Researchers discover how certain bacteria may safeguard plant growth during a drought, making way for strategies to improve crop productivity.

    Sierra Snowpack Could Drop Significantly By End of Century

    A future warmer world will almost certainly feature a decline in fresh water from the Sierra Nevada mountain snowpack. Now a new study by Lawrence Berkeley National Laboratory that analyzed the headwater regions of California's 10 major reservoirs, representing nearly half of the state's surface storage, found they could see on average a 79 percent drop in peak snowpack water volume by 2100.

    The Biermann Battery Effect: Spontaneous Generation of Magnetic Fields and Their Severing

    The mechanism responsible for creating intense magnetic fields in laser-driven plasmas also helps tear the fields apart.

    Compelling Evidence for Small Drops of Perfect Fluid

    Nuclear physicists analyzing data from the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC) have published additional evidence that collisions of miniscule projectiles with gold nuclei create tiny specks of the perfect fluid that filled the early universe.


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    DOE approves technical plan and cost estimate to upgrade Argonne facility; Project will create X-rays that illuminate the atomic scale, in 3D

    The U.S. Department of Energy has approved the technical scope, cost estimate and plan of work for an upgrade of the Advanced Photon Source, a major storage-ring X-ray source at Argonne.

    Costas Soukoulis elected to National Academy of Inventors

    Costas Soukoulis, Ames Laboratory senior scientist and Iowa State University Frances M. Craig Endowed Chair and Distinguished Professor, has been named as a 2018 National Academy of Inventors (NAI) Fellow.

    Biophysicist F. William Studier Elected Fellow of the National Academy of Inventors

    F. William Studier, a Senior Biophysicist Emeritus at the U.S. Department of Energy's Brookhaven National Laboratory and Adjunct Professor of Biochemistry at Stony Brook University, has been elected as a Fellow of the National Academy of Inventors (NAI). He is among 148 renowned academic inventors being recognized by NAI for 2018.

    Blast to the future

    A grant from DOE's Technology Commercialization Fund will help researchers at Argonne and industry partners seek improvements to U.S. manufacturing by making discovery and design of new materials more efficient.

    Department of Energy to Provide $24 Million for Computer-Based Materials Design

    The U.S. Department of Energy (DOE) announced plans to provide $24 million in new and renewal research awards to advance the development of sophisticated software for computer-based design of novel materials.

    Argonne scientists recognized for decades of pioneering leadership in research

    Argonne scientists Ali Erdemir and Jack Vaughey were named 2018 Fellows of the American Association for the Advancement of Science (AAAS).

    Kurfess, Smith join ORNL to lead advanced manufacturing initiatives

    Two leaders in US manufacturing innovation, Thomas Kurfess and Scott Smith, are joining the Department of Energy's Oak Ridge National Laboratory to support its pioneering research in advanced manufacturing.

    Four Berkeley Lab Scientists Named AAAS Fellows

    Four Berkeley Lab scientists - Allen Goldstein, Sung-Hou Kim, Susannah Tringe, and Katherine Yelick - have been named Fellows of the American Association for the Advancement of Science, the world's largest general scientific society.

    U.S. Department of Energy to Host Nationwide CyberForce Competition(tm) December 1

    Students from dozens of colleges/universities will participate in the U.S. Department of Energy's CyberForce Competition(tm) this weekend

    Seven ORNL researchers named 2019 INCITE award winners

    Seven researchers from the Department of Energy's Oak Ridge National Laboratory have been chosen by the Innovative and Novel Computational Impact on Theory and Experiment, also known as INCITE, program to lead scientific investigations that require the nation's most powerful computers. The ORNL-based projects span a broad range of the scientific spectrum and represent the potential of high-performance computing in ensuring America's scientific competitiveness and energy security.


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    Ice Formed by Contact Freezing: Pressure Matters, Not Just Temperature

    Distortion of water droplet surface may increase the likelihood of the droplet freezing.

    Future Loss of Arctic Sea-Ice Cover Could Contribute to the Substantial Decrease in California's Rainfall

    A new modeling framework helps understand the consequences of future sea-ice loss in the Arctic.

    Drawn into a Whirlpool: A New Way to Stop Dangerous Fast Electrons in a Fusion Device

    A new phenomena forms vortices that trap particles, impeding electron avalanches that harm fusion reactors.

    During Droughts, Bacteria Help Sorghum Continue Growing

    Researchers discover how certain bacteria may safeguard plant growth during a drought, making way for strategies to improve crop productivity.

    The Biermann Battery Effect: Spontaneous Generation of Magnetic Fields and Their Severing

    The mechanism responsible for creating intense magnetic fields in laser-driven plasmas also helps tear the fields apart.

    Subtlety and the Selective Art of Separating Lanthanides

    Unexpected molecular interactions involving water clusters have a subtle, yet profound, effect on extractants picking their targets.

    Review Examines the Science and Needs of Nitrogen-Based Transformations

    Advances in biochemistry and catalysis could lead to faster, greener nitrogen-rich fertilizer.

    Quickly Capture Tiny Particles Reacting

    New method takes a snapshot every millisecond of groups of light-scattering particles, showing what happens during industrially relevant reactions.

    New Technology Consistently Identifies Proteins from a Dozen Cells

    A new platform melding microfluidics and robotics allows more in-depth bioanalysis with fewer cells than ever before.

    Optimal Foraging: How Soil Microbes Adapt to Nutrient Constraints

    How microbial communities adjust to nutrient-poor soils at the genomic and proteomic level gives scientists insights into land use.


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