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Artist's depiction of a type IV secretion system nestled within a bacterial cell membrane. This structure shoots out thousands of toxic molecules (purple) into human cells during an infection. Credit: Caltech Experts predict that by 2050, antibiotic-resistant bacteria will cause as many deaths as cancer. Now, for the first time, Caltech scientists have created a 3-D image of a molecular structure that many different bacteria use to pump toxins into human cells and spread antibiotic-resistance genes to other bacteria. Understanding the architecture of this structure is a first step toward combating its effects. The study was conducted in the laboratory of Grant Jensen, professor of biophysics and biology and Howard Hughes Medical Institute Investigator. A paper describing the work first appeared online in the March 23 issue of EMBO Reports. The researchers looked specifically at Legionella, the bacteria that causes Legionnaires' disease, a severe and often lethal form of pneumonia. When Legionella invades a human cell, it wraps itself in a protective vesicle and opens the molecular structure, known as a type IV secretion system. The molecular "machine" sits in the cell membrane of the bacterium and proceeds to shoot tens of thousands of toxic molecules—hundreds of different types—into the human cell, hijacking cellular pathways and overwhelming the cell's defenses. Some type IV secretion systems are thought to be instrumental in spreading antibiotic-resistance genes throughout the bacterial population. "Understanding the structure of the type IV system is crucial to developing new antibiotics to disable it," says first author and postdoctoral scholar Debnath Ghosal. "While this study focuses only on the secretion system of Legionella, a very similar machine is used by many bacteria—such as the pathogens that cause stomach cancer, Q fever, and whooping cough." To image the structure—which, at 40 nanometers in diameter, is about 1,000 times too small to be seen by the human eye—the researchers employed a technique called electron cryotomography. In this method, bacteria are frozen alive and then rotated under a powerful electron microscope to create a series of 2-D images that can be digitally reconstructed into a 3-D picture. This was the first-ever image of a type IV machine within a bacterium. The imaging revealed that the structure is shaped into concentric arches, like the symbol for Wi-Fi. Understanding the structure should eventually aid efforts to design drugs that can block the machine. Developing a drug that would disable even one core protein component of the secretion system, Ghosal says, would enable human cells to fight back against the bacterial infection. "Most current antibiotics focus on destroying the cellular envelope that encompasses a bacterial cell, preventing it from replicating," says Jensen. "Developing new antibiotics that target different aspects of the bacterial cell, such as the type IV secretion system, would enable us to block infections in additional ways." The paper is titled "In situ structure of the Legionella Dot/Icm type IV secretion system by electron cryotomography." In addition to Ghosal and Jensen, coauthors are Caltech research scientist Yi Wei Chang, Kwang Cheol Jeong of the Washington University School of Medicine and the University of Florida, and Joseph Vogel of the Washington University School of Medicine. Funding was provided by the National Institutes of Health and the National Institute of Allergy and Infectious Diseases. Explore further: Spread of antibiotic resistance understood by unravelling bacterial secretion system


News Article | August 2, 2017
Site: www.eurekalert.org

Heidelberg, 2 August 2017 - There is increasing evidence that post-traumatic stress disorder (PTSD) increases the risk of developing dementia later in life. Researchers at the University Medical Center Goettingen, Germany, now shed light on the molecular mechanism that links the two disorders. The research is published today in The EMBO Journal. PTSD is a brain disorder that can occur after experiencing a traumatic event. Individuals with PTSD frequently relive the traumatic event, often triggered by stimuli similar to those that accompanied the trauma. A number of epidemiological studies have shown that individuals suffering from PTSD are more prone to acquiring Alzheimer's disease later in their lives. Unravelling the molecular underpinnings of this correlation will help to identify targeted therapies. The research team in Goettingen identified such a molecular link by showing that Formin 2 is deregulated in PTSD and Alzheimer's disease patients. To investigate this link further, the researchers showed that Formin 2 mutant mice show PTSD phenotypes at an early age and develop age-related memory decline. On the molecular level, Formin 2 is active in the brain, where it regulates the dynamics of the cytoskeleton, the structure that helps cells to maintain their shape and internal organization. It is required for neuronal cell contacts to change and to ease off again after they have been strengthened by learning. "Our hypothesis was that various risk factors eventually cause an aberrant activation of many genes that contribute to Alzheimer's disease. One of these factors could be developing PTSD via a process that involves Formin 2," said Farahnaz Sananbenesi, lead researcher of the study. To test this idea, the researchers undertook a comprehensive analysis of gene activity in Formin 2 mutant mice. Indeed, whereas young mice lacking Formin 2 were hardly different from normal mice, a deregulation of hundreds of genes built up as they aged. The researchers also found that the drug Vorinostat, which ameliorates PTSD phenotypes in younger mice, enhanced memory in aged Formin 2-deficient mice. "Our results indicate that it may be possible to develop therapeutic strategies for PTSD patients that, at the same time, lower the risk to develop Alzheimer's disease," said André Fischer who coordinated the study together with Dr. Sananbenesi. Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for dementia Roberto Carlos Agis-Balboa, Paulo Pinhero, Nelson Rebola, Cemil Kerimoglu, Eva Benito, Michael Gertig, Sanaz Bahari-Javan, Gaurav Jain, Susanne Burkhardt, Ivana Delalle, Alexander Jatzko, Markus Dettenhofer, Patricia A. Zunszain, Andrea Schmitt, Peter Falkai, Julius C. Pape, Elisabeth B. Binder, Christophe Mulle, Andre Fischer & Farahnaz Sananbenesi DOI 10.15252/embj.201796821 EMBO Press stands for publishing impactful, high quality and reliable research across the biosciences in its four journals, The EMBO Journal, EMBO Reports, Molecular Systems Biology and EMBO Molecular Medicine. EMBO Press pioneered the transparent editorial process in order to provide a rapid, fair and efficient publication process. Through developing and employing Source Data tools, EMBO Press works towards improving data transparency, reuse and discoverability. Through dedicated data integrity checks, it ensures the publication of reliable data. All submitted manuscripts are subject to scooping protection, which extends to manuscripts published on preprint servers. As a co-signatory of the San Francisco Declaration for Research Assessment, EMBO Press is an advocate for moving away from impact factors as a mechanism for research assessment. EMBO is an organization of more than 1700 leading researchers that promotes excellence in the life sciences. The major goals of the organization are to support talented researchers at all stages of their careers, stimulate the exchange of scientific information, and help build a European research environment where scientists can achieve their best work. EMBO helps young scientists to advance their research, promote their international reputations and ensure their mobility. Courses, workshops, conferences and scientific journals disseminate the latest research and offer training in techniques to maintain high standards of excellence in research practice. EMBO helps to shape science and research policy by seeking input and feedback from our community and by following closely the trends in science in Europe. ?For more information: http://www.


News Article | June 8, 2017
Site: www.eurekalert.org

Heidelberg, 8 June 2017 - Maya Schuldiner from the Weizmann Institute of Science in Israel is the recipient of the 2017 EMBO Gold Medal. She receives the award for significantly advancing the understanding of protein synthesis, trafficking and quality control. The EMBO Gold Medal is awarded annually and recognizes outstanding contributions to the life sciences in Europe by young independent group leaders. "Young independent group leaders are essential for a strong research ecosystem," says EMBO Director Maria Leptin. "They identify important unanswered questions, explore new experimental approaches, and act as mentors for the next generation of scientists. The EMBO Gold Medal highlights some of the remarkable achievements through which this group of scientists drives our understanding of biology." Schuldiner uses yeast as a model organism to examine two aspects of organelle cell biology: how proteins that reside inside organelles are targeted to the correct destination and how different organelles interact with each other to drive cell function. Specifically, she focuses on revealing new proteins and their functions in these processes. To achieve this her lab combines a wide variety of high-throughout screening techniques with cell biological, genetic and biochemical approaches. EMBO Member and previous EMBO Gold Medal recipient Matthew Freeman, University of Oxford, UK, describes Schuldiner as "an exceptional scientist, an intellectual leader, and an inspiring character. Maya's research stands out for successfully merging advanced high-throughput technologies with the ability to ask smart, focused questions." Maya Schuldiner describes receiving the EMBO Gold Medal as "a highlight in my career." She continues: "I'm excited to see that when one is truly passionate about being a scientist and just as devoted to being a mother it is possible to make both work together. And I would like to thank my husband Oren Schuldiner, because without his true partnership in raising our children I could not be as committed to science." She will receive the EMBO Gold Medal and an award of 10,000 euros at an award ceremony at the ASCB | EMBO 2017 meeting in Philadelphia, USA, on 4 December, during which she will also present her research. Maya Schuldiner carried out a PhD in developmental biology at The Hebrew University in Jerusalem, Israel, under the supervision of Nissim Benvenisty. She switched fields to cellular biology for her postdoctoral research, which she carried out in the laboratory of Jonathan Weissman at the University of California, San Francisco. In 2008, she moved back to Israel to establish her own laboratory at the Weizmann Institute of Sciences in Rehovot. The research in her laboratory focuses on using high-throughput screening and imaging techniques to discover novel functions of proteins in yeast. Maya Schuldiner received a Human Frontiers Science Program Career Development Award in 2008 and became a member of the EMBO Young Investigator Programme in 2011. She received a European Research Council Consolidator Grant in 2015 and currently holds the Dr. Omenn and Martha Darling Professorial Chair in Molecular Genetics. She is passionate about mentoring and has established a course on combining motherhood and career and a course on scientific soft-skills, which she currently teaches at the Weizmann Institute. EMBO is an organization of more than 1700 leading researchers that promotes excellence in the life sciences. The major goals of the organization are to support talented researchers at all stages of their careers, stimulate the exchange of scientific information, and help build a European research environment where scientists can achieve their best work. EMBO helps young scientists to advance their research, promote their international reputations and ensure their mobility. Courses, workshops, conferences and scientific journals disseminate the latest research and offer training in techniques to maintain high standards of excellence in research practice. EMBO helps to shape science and research policy by seeking input and feedback from our community and by following closely the trends in science in Europe.


News Article | June 16, 2017
Site: www.eurekalert.org

Heidelberg, June 16, 2017 - EMBO announces today that 65 outstanding life scientists have been elected to its membership, joining a group of more than 1700 of the best researchers in Europe and around the world. The total number includes 56 EMBO Members residing in 19 Member States of the European Molecular Biology Conference (EMBC) and nine EMBO Associate Members currently working in the USA and Japan. "Election to the EMBO Membership is recognition of research excellence, and I am pleased to welcome so many great scientists to our organisation," says EMBO Director Maria Leptin. She continues: "We received more nominations than ever before during this election cycle, which pays tribute to the strength and diversity of the European life sciences. Drawing on our new members' expertise and insight will be invaluable in helping EMBO to deliver and strengthen its programmes and activities in the years to come." EMBO Members are actively involved in the execution of the organisation's initiatives by evaluating applications for EMBO funding and by serving on EMBO Council, Committees and Editorial Boards. New EMBO Members and Associate Members will be formally welcomed at the EMBO Members' Meeting in Heidelberg 18-20 October 2017. An online directory with all existing and new EMBO Members is available at people.embo.org. Eva Benkova Institute of Science and Technology Austria (IST), Klosterneuburg, AT Fátima Gebauer Hernández Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, ES Daniel W. Gerlich Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, AT Ben Lehner Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, ES Jonathan Weissman HHMI and University of California, San Francisco, US EMBO is an organization of more than 1700 leading researchers that promotes excellence in the life sciences. The major goals of the organization are to support talented researchers at all stages of their careers, stimulate the exchange of scientific information, and help build a European research environment where scientists can achieve their best work. EMBO helps young scientists to advance their research, promote their international reputations and ensure their mobility. Courses, workshops, conferences and scientific journals disseminate the latest research and offer training in techniques to maintain high standards of excellence in research practice. EMBO helps to shape science and research policy by seeking input and feedback from our community and by following closely the trends in science in Europe. For more information: http://www.


News Article | September 15, 2017
Site: www.eurekalert.org

Amsterdam and Heidelberg, 15 September 2017 - SourceData (sourcedata.embo.org), an open platform from EMBO, designed to make published scientific data easily findable, has won the 2017 ALPSP Award for Innovation in Publishing. The results were announced on 14 September 2017 at the ALPSP 10th Anniversary Conference and Awards in Amsterdam. The Association of Learned and Professional Society Publishers (ALPSP) represents organizations and institutions that publish scholarly and professional content around the world. The award recognizes innovative projects that are of significant value to scholarly communication. SourceData was one of six projects shortlisted from over 40 submissions and was declared one of two winners along with Publons, a cross-publisher platform for researchers to collate and verify evidence of their work as an editor or peer reviewer. SourceData project lead, Thomas Lemberger, accepted the award, stating that "the project grew out of a simple idea to make it easier for scientists to find and use the data published in journal articles." SourceData describes the data published in figures using a machine-readable format that identifies the biological entities contained in the figures and the causal relationships between them. This format allows researchers to search directly for data on specific research questions and to easily navigate between related figures, including those published in different papers. "It is a great honour to have the innovation and value of SourceData recognised by publishers," said Lemberger. "SourceData can provide publishers with new tools to help their readers find relevant content and can give scientists an easier way to search the published literature for pertinent data." SourceData was developed at EMBO in collaboration with the Swiss Institute of Bioinformatics and supported by the Robert Bosch Stiftung. In September 2016, the SmartFigures Lab (smartfigures.net), SourceData's first implementation in a publishing environment, was launched in partnership with publishers Wiley and developers 67 Bricks. SourceData makes use of the information routinely provided by authors to describe their results, including figure legends, axis labels and figure contents. The resulting description captures the elements studied, such as genes or proteins, and their role: whether they were manipulated or observed. Figures can then be linked to each other based on their common elements and searched based on their tested relationships. SourceData provides a suite of applications including SmartFigures: enhanced figures containing links to related results and data that can be embedded in online publications, DataSearch: a search engine that finds published figures based on their data content, and MetaFig: a curation interface that offers computer-assisted importing of new figures into the SourceData format. The SourceData team plans to continue engaging with the community of authors, researchers and publishers to promote broad adoption of the platform. For more information about SourceData, visit sourcedata.embo.org EMBO is an organization of more than 1700 leading researchers that promotes excellence in the life sciences. The major goals of the organization are to support talented researchers at all stages of their careers, stimulate the exchange of scientific information, and help build a European research environment where scientists can achieve their best work. EMBO helps young scientists to advance their research, promote their international reputations and ensure their mobility. Courses, workshops, conferences and scientific journals disseminate the latest research and offer training in techniques to maintain high standards of excellence in research practice. EMBO helps to shape science and research policy by seeking input and feedback from our community and by following closely the trends in science in Europe. ?For more information: http://www.


Pulverer B.,EMBO
EMBO Journal | Year: 2014

New guidelines for the reporting of research and source data enhance the interpretation and reproducibility of published research. New guidelines for the reporting of research and source data enhance the interpretation and reproducibility of published research. © 2014 The Author.


Pulverer B.,EMBO
EMBO Journal | Year: 2014

Systematic image screening at EMBO Press uncovers many problems, most of which can be resolved. Standardized pre-publication image screening would make for a more reliable literature. Flagging putative image manipulation post-publication remains an important control mechanism, but must not fall victim to an overzealous response. The STAP stem cell papers are a case in point. Systematic image screening at EMBO Press uncovers many irregularities, which are thereby prevented from entering the scientific literature. Such mechanisms may have helped thwart publication of manipulated images in recent high-profile papers. © 2014 The Author.


Pulverer B.,EMBO
EMBO Journal | Year: 2015

A reliable scientific literature is crucial for an efficient research process. Peer review remains a highly successful quality assurance mechanism, but it does not always prevent data and image aberrations and the publication of flawed data. Journals need to be in a position to detect such problems and take proportionate action. Publishers should apply consistent policies to correcting the published literature and adopt versioning. The scientific community ought to encourage corrections. Peer review is a successful quality assurance mechanism for a reliable scientific literature, but it does not always prevent the publication of flawed data. Journals need to be in a position to assess data and image aberrations and correct the literature. The scientific community should encourage author-initiated corrections. © 2015 The Author.


Pulverer B.,EMBO
EMBO Journal | Year: 2015

The San Francisco Declaration on Research Assessment (DORA) points out that using the Journal Impact Factor as a proxy measure for the value or quality of specific research and individual scientists leads to biased research assessment. How can we resist misusing metrics? © 2015 The Author.


An interview with Jeffery Taubenberger from NIAID about how understanding the evolution of influenza could inform vaccine development and public health measures to deal with flu pandemics. © 2014 The Author.

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