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News Article | May 10, 2017
Site: www.eurekalert.org

Reported in Nature today, one of the largest sets of high quality human induced pluripotent stem cell lines from healthy individuals has been produced by a consortium involving the Wellcome Trust Sanger Institute. Comprehensively annotated and available for independent research*, the hundreds of stem cell lines are a powerful resource for scientists studying human development and disease. With collaborative partners from King's College London, the European Bioinformatics Institute, the University of Dundee and the University of Cambridge, the study also investigates in unprecedented detail the extensive variation between stem cells from different healthy people. Technological advancements have made it possible to take an adult cell and use specific growth conditions to turn back the clock - returning it to an early embryonic state. This results in an induced pluripotent stem cell (iPSC), which can develop into any type of cell in the body. These iPSCs have huge scientific potential for studying the development and the impact of diseases including cancer, Alzheimer's, and heart disease. However, the process of creating an iPSC is long and complicated and few laboratories have the facilities to characterise their cells in a way that makes them useful for other scientists to use. The Human Induced Pluripotent Stem Cell Initiative (HipSci) project used standardised methods to generate iPSCs on a large scale to study the differences between healthy people. Reference sets of stem cells were generated from skin biopsies donated by 301 healthy volunteers, creating multiple stem cell lines from each person. The researchers created 711 cell lines and generated detailed information about their genome, the proteins expressed in them, and the cell biology of each cell line. Lines and data generated by this initiative are available to academic researchers and industry. Dr Daniel Gaffney, a lead author on the paper, from the Wellcome Trust Sanger Institute, said: "We have created a comprehensive, high quality reference set of human induced pluripotent stem cell lines from healthy volunteers. Each of these stem cell lines has been extensively characterised and made available to the wider research community along with the annotation data. This resource is a stepping stone for researchers to make better cell models of many diseases, because they can study disease risk in many cell types, including those that are normally inaccessible." By creating more than one stem cell line from each healthy individual, the researchers were able to determine the similarity of stem cell lines from the same person. Prof Fiona Watt, a lead author on the paper and co-principal investigator of HipSci, from King's College London, said: "Many other efforts to create stem cells focus on rare diseases. In our study, stem cells have been produced from hundreds of healthy volunteers to study common genetic variation. We were able to show similar characteristics of iPS cells from the same person, and revealed that up to 46 per cent of the differences we saw in iPS cells were due to differences between individuals. These data will allow researchers to put disease variations in context with healthy people." The project, which has taken 4 years to complete, required a multidisciplinary approach with many different collaborators, who specialised in different aspects of creating the cell lines and characterising the data. Dr Oliver Stegle, a lead author on the paper, from the European Bioinformatics Institute, said: "This study was only possible due to the large scale, systematic production and characterisation of the stem cell lines. To help us to understand the different properties of the cells, we collected extensive data on multiple molecular layers, from the genome of the lines to their cell biology. This type of phenotyping required a whole facility rather than just a single lab, and will provide a huge resource to other scientists. Already, the data being generated have helped to gain a clearer picture of what a typical human iPSC cell looks like." Dr Michael Dunn, Head of Genetics and Molecular Sciences at Wellcome, said: "This is the fantastic result of many years of work to create a national resource of high quality, well-characterised human induced pluripotent stem cells. This has been a significant achievement made possible by the collaboration of researchers across the country with joint funding provided by Wellcome and the MRC. It will help to provide the knowledge base to underpin a huge amount of future research into the effects of our genes on health and disease. By ensuring this resource is openly available to all, we hope that it will pave the way for many more fascinating discoveries." *Data and cell lines from this study are being made available through http://www. , the European Collection of Authenticated Cell Cultures (ECACC) and the European Bank for Induced Pluripotent Stem Cells (EBiSC). Hipsci brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a global induced pluripotent stem cell resource for the research community. http://www. King's College London is one of the top 25 universities in the world (2016/17 QS World University Rankings) and among the oldest in England. King's has more than 29,600 students (of whom nearly 11,700 are graduate students) from some 150 countries worldwide, and some 8,000 staff. King's has an outstanding reputation for world-class teaching and cutting-edge research. In the 2014 Research Excellence Framework (REF), eighty-four per cent of research at King's was deemed 'world-leading' or 'internationally excellent' (3* and 4*). Since our foundation, King's students and staff have dedicated themselves in the service of society. King's will continue to focus on world-leading education, research and service, and will have an increasingly proactive role to play in a more interconnected, complex world. Visit our website to find out more about Vision 2029, King's strategic vision for the next 12 years to 2029, which will be the 200th anniversary of the founding of the university. http://www. The European Bioinformatics Institute (EMBL-EBI) is a global leader in the storage, analysis and dissemination of large biological datasets. EMBL-EBI helps scientists realise the potential of 'big data' by enhancing their ability to exploit complex information to make discoveries that benefit humankind. EMBL-EBI is at the forefront of computational biology research, with work spanning sequence analysis methods, multi-dimensional statistical analysis and data-driven biological discovery, from plant biology to mammalian development and disease. We are part of the European Molecular Biology Laboratory (EMBL), an international, innovative and interdisciplinary research organisation funded by 22 member states and two associate member states, and are located on the Wellcome Genome Campus, one of the world's largest concentrations of scientific and technical expertise in genomics. http://www. The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease. http://www. Wellcome exists to improve health for everyone by helping great ideas to thrive. We're a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate. http://www.

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

Relapse is now the main cause of death for breast cancer patients. Researchers at EMBL have found that, in mice, the tumour cells that survive therapy and eventually cause a relapse have specific traits that distinguish them from healthy cells. In a study published today in the Journal of Clinical Investigation, the scientists revealed that two of these traits could be promising targets for treatments to reduce tumour recurrence in breast cancer patients. "Our results suggest that residual cells retain an "oncogenic memory" that could be exploited to develop drugs against breast cancer recurrence," says Martin Jechlinger, who led the research at EMBL. Thanks to improvements in primary care, more and more breast cancer patients survive the initial tumour. Although treatments like chemotherapy and mastectomies aim to eliminate all of a patient's tumour cells, breast cancer cells that survive these initial therapies often reinitiate growth, causing a relapse further down the line. These residual cells are difficult to identify and analyse because, until they relapse, they look and act as normal cells. This means breast cancer relapse has remained largely unexplored, and makes it difficult to predict if and when a patient will experience relapse. "We found that residual cells have molecular traits that clearly distinguish them from normal breast tissue, and seem to cause relapse," Jechlinger explains. "When we treated those features in mice, their tumours were less likely to recur." Jechlinger and colleagues found that, compared to healthy cells, residual cancer cells have altered lipid metabolism. This contributes to maintaining high levels of "reactive oxygen species" -- chemically reactive molecules that are known to damage DNA. The scientists think that this damage triggers the relapse. The team then compared the findings from the mouse model to samples from breast cancer patients, thanks to collaborators at the European Institute of Oncology in Milan, Italy, and the National Centre for Tumour Diseases in Heidelberg, Germany. The two sets of results were consistent, which suggests they could be useful to understand and treat breast cancer recurrence in humans. "Every patient is different and every story is unique, but our results suggest that lipid metabolism is an exciting therapeutic target to reduce breast cancer recurrence," says Kristina Havas, who carried out much of the research in Jechlinger's lab at EMBL. In this study, to isolate and characterize the cells which survived therapy, the researchers used organotypic structures, or organoids. Organoids are small clusters of cells cultured outside the body that accurately mimic some of the structure and function of real organs. Organoids can be used for drug testing, investigating personalised therapies and understanding organ development.

News Article | May 19, 2017
Site: news.europawire.eu

HEIDELBERG, 19-May-2017 — /EuropaWire/ — The German National Academy of Sciences, Leopoldina, today welcomes EMBO Director Maria Leptin as one of its members. Election to the Leopoldina membership is the highest academic honour awarded by an institution in Germany and it is bestowed on scientists who are experts in their fields. Maria Leptin, together with 14 other eminent researchers from Germany and abroad, was elected in 2016, and will today be officially welcomed at a ceremony in Halle (Saale), Germany. Following the presentation of the membership certificates, Maria Leptin will deliver a lecture on the role of cellular coordination during the development of organs and whole organisms. Through her election, Maria Leptin became part of a membership of over 1,500 individuals from more than 30 countries. Other EMBO Members elected to the Leopoldina Membership in 2016 include Aaron Ciechanover, Haifa, Israel, Veit Hornung, Munich, Germany, Edvard Moser, Trondheim, Norway, May-Britt Moser, Trondheim, Norway, Christian Spahn, Berlin, Germany. For more information (in German): https://www.leopoldina.org/de/presse/pressemitteilungen/pressemitteilung/press/2487/ Maria Leptin received her PhD in 1983 for work on B cell activation carried out at the Basel Institute for Immunology under the supervision of Fritz Melchers. She switched to the study of development in Drosophila when she joined the laboratory of Michael Wilcox at the Medical Research Council’s Laboratory of Molecular Biology (LMB) in Cambridge, UK, for her postdoctoral work on Drosophila integrins. After a research visit at the lab of Pat O’Farrell at the University of California San Francisco (UCSF), where she began studying gastrulation, she spent the years from 1989 to 1994 as a group leader at the Max Planck Institute in Tübingen. In 1994, she became Professor at the Institute of Genetics University of Cologne. In January 2010 Maria Leptin became the Director of EMBO and established a research group in Heidelberg at the European Molecular Biology Laboratory (EMBL). The group studies the development of complex cell shapes in the respiratory system of Drosophila and the role of RNA localisation in generating cell shape. Professor Leptin is an elected member of EMBO, the Academia Europaea and the German National Academy of Sciences (Leopoldina). She also serves on the editorial boards of Developmental Cell, Developmental Biology and on advisory boards of several academic institutions.

News Article | April 25, 2017
Site: www.businesswire.com

KIEV, Ukraine--(BUSINESS WIRE)--Enamine Ltd., a chemical company, producer of novel chemical building blocks and screening libraries, and the European Molecular Biology Laboratory (EMBL) have agreed to establish a collaboration whereby Enamine provides library synthesis, medicinal chemistry and biological services for the discovery and development of novel small molecules against EMBL’s proprietary anti-cancer targets. The collaboration involves the deployment of a team of Full Time Equivalent

News Article | April 20, 2017
Site: www.chromatographytechniques.com

Scientists at the Centre for Genomic Regulation (CRG) in Barcelona and the Josep Carreras Leukaemia Research Institute and The Institute for Health Science Research Germans Trias i Pujol (IGTP) in Badalona, Spain, have discovered that the impact of environmental change can be passed on in the genes of tiny nematode worms for at least 14 generations—the most that has ever been seen in animals. The findings will be published on Friday, April 21, in the journal Science. Led by Ben Lehner, group leader at the EMBL-CRG Systems Biology Unit and ICREA and AXA professor, together with Tanya Vavouri from the Josep Carreras Leukaemia Research Institute and the Institute for Health Science Research Germans Trias i Pujol (IGTP), the researchers noticed that the impact of environmental change can be passed on in the genes for many generations while studying C. elegans worms carrying a transgene array -- a long string of repeated copies of a gene for a fluorescent protein that had been added into the worm genome using genetic engineering techniques. If the worms were kept at 20 degrees Celsius, the array of transgenes was less active, creating only a small amount of fluorescent protein. But shifting the animals to a warmer climate of 25 degrees significantly increased the activity of the transgenes, making the animals glow brightly under ultraviolet light when viewed down a microscope. When these worms were moved back to the cooler temperature, their transgenes were still highly active, suggesting they were somehow retaining the "memory" of their exposure to warmth. Intriguingly, this high activity level was passed on to their offspring and onwards for seven subsequent generations kept solely at 20 degrees, even though the original animals only experienced the higher temperature for a brief time. Keeping worms at 25 degrees for five generations led to the increased transgene activity being maintained for at least 14 generations once the animals were returned to cooler conditions. Although this phenomenon has been seen in a range of animal species - including fruit flies, worms and mammals including humans - it tends to fade after a few generations. These findings represent the longest maintenance of transgenerational environmental "memory" ever observed in animals to date. "We discovered this phenomenon by chance, but it shows that it's certainly possible to transmit information about the environment down the generations," says Lehner. "We don't know exactly why this happens, but it might be a form of biological forward-planning," adds first author of the study and CRG Alumnus, Adam Klosin. "Worms are very short-lived, so perhaps they are transmitting memories of past conditions to help their descendants predict what their environment might be like in the future," adds Vavouri. Comparing the transgenes that were less active with those that had become activated by the higher temperature, Lehner and his team discovered crucial differences in a type of molecular "tag" attached to the proteins packaging up the genes, known as histone methylation. Transgenes in animals that had only ever been kept at 20 degrees had high levels of histone methylation, which is associated with silenced genes, while those that had been moved to 25 degrees had largely lost the methylation tags. Importantly, they still maintained this reduced histone methylation when moved back to the cooler temperature, suggesting that it is playing an important role in locking the memory into the transgenes. The researchers also found that repetitive parts of the normal worm genome that look similar to transgene arrays also behave in the same way, suggesting that this is a widespread memory mechanism and not just restricted to artificially engineered genes.

Letunic I.,Biobyte Solutions GmbH | Doerks T.,EMBL | Bork P.,EMBL
Nucleic Acids Research | Year: 2015

SMART (Simple Modular Architecture Research Tool) is a web resource (http://smart.embl.de/) providing simple identification and extensive annotation of protein domains and the exploration of protein domain architectures. In the current version, SMART contains manually curated models for more than 1200 protein domains, with ∼200 new models since our last update article. The underlying protein databases were synchronized with UniProt, Ensembl and STRING, bringing the total number of annotated domains and other protein features above 100 million. SMART's 'Genomic' mode, which annotates proteins from completely sequenced genomes was greatly expanded and now includes 2031 species, compared to 1133 in the previous release. SMART analysis results pages have been completely redesigned and include links to several new information sources. A new, vector-based display engine has been developed for protein schematics in SMART, which can also be exported as highresolution bitmap images for easy inclusion into other documents. Taxonomic tree displays in SMART have been significantly improved, and can be easily navigated using the integrated search engine. © The Author(s) 2014.

Maitre J.-L.,EMBL | Heisenberg C.-P.,IST Austria
Current Biology | Year: 2013

Cadherins are transmembrane proteins that mediate cell-cell adhesion in animals. By regulating contact formation and stability, cadherins play a crucial role in tissue morphogenesis and homeostasis. Here, we review the three major functions of cadherins in cell-cell contact formation and stability. Two of those functions lead to a decrease in interfacial tension at the forming cell-cell contact, thereby promoting contact expansion - first, by providing adhesion tension that lowers interfacial tension at the cell-cell contact, and second, by signaling to the actomyosin cytoskeleton in order to reduce cortex tension and thus interfacial tension at the contact. The third function of cadherins in cell-cell contact formation is to stabilize the contact by resisting mechanical forces that pull on the contact. © 2013 Elsevier Ltd.

Letunic I.,EMBL | Doerks T.,EMBL | Bork P.,EMBL
Nucleic Acids Research | Year: 2012

SMART (Simple Modular Architecture Research Tool) is an online resource (http://smart.embl.de/) for the identification and annotation of protein domains and the analysis of protein domain architectures. SMART version 7 contains manually curated models for 1009 protein domains, 200 more than in the previous version. The current release introduces several novel features and a streamlined user interface resulting in a faster and more comfortable workflow. The underlying protein databases were greatly expanded, resulting in a 2-fold increase in number of annotated domains and features. The database of completely sequenced genomes now includes 1133 species, compared to 630 in the previous release. Domain architecture analysis results can now be exported and visualized through the iTOL phylogenetic tree viewer. 'metaSMART' was introduced as a novel subresource dedicated to the exploration and analysis of domain architectures in various metagenomics data sets. An advanced full text search engine was implemented, covering the complete annotations for SMART and Pfam domains, as well as the complete set of protein descriptions, allowing users to quickly find relevant information. © The Author(s) 2011. Published by Oxford University Press.

Letunic I.,EMBL | Bork P.,EMBL
Nucleic Acids Research | Year: 2011

Interactive Tree Of Life (http://itol.embl.de) is a web-based tool for the display, manipulation and annotation of phylogenetic trees. It is freely available and open to everyone. In addition to classical tree viewer functions, iTOL offers many novel ways of annotating trees with various additional data. Current version introduces numerous new features and greatly expands the number of supported data set types. Trees can be interactively manipulated and edited. A free personal account system is available, providing management and sharing of trees in user defined workspaces and projects. Export to various bitmap and vector graphics formats is supported. Batch access interface is available for programmatic access or inclusion of interactive trees into other web services. © 2011 The Author(s).

The present invention relates to unnatural amino acids comprising a cyclooctynyl or trans-cyclooctenyl analog group and having formula (I) or an acid or base addition salt thereof. The invention also relates to the use of said unnatural amino acids, kits and processes for preparation of polypeptides that comprise one or more than one cyclooctynyl or trans-cyclooctenyl analog group. These polypeptides can be covalently modified by in vitro or in vivo reaction with compounds comprising an azide, nitrile oxide, nitrone, diazocarbonyl or 1,2,4,5-tetrazine group.

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