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Agency: Cordis | Branch: H2020 | Program: RIA | Phase: EINFRA-9-2015 | Award Amount: 2.96M | Year: 2015

Genomics is probably the fastest evolving field in current science. A decade ago our main concern was to obtain the sequence (the 1D code) of the genome; but today the big challenges are to determine how genotype information is transferred into phenotype, and how pathological phenotypic changes can be predicted from genome alterations. While investigating these points, we have realized that a part of the regulation of gene expression is implicitly coded in the way in which chromatin is folded. As technology has advanced and information of the folded state of chromatin has emerged, a new branch of genomics (3D/4D genomics) has emerged. Hundreds of laboratories are now defining a young and active community that, though in the end concerned with the same scientific problem, uses many different approaches to study it that individually target radically different length and timescales. The community faces severe practical problems related to: i) how huge, noisy, and diverse data related to widely different size and time scales can be integrated, ii) the lack of standardized analysis and simulation tools, iii) the complete disconnection of associated informatics databases, and iv) the lack of validated and flexible visualization engines. MuG is born at the critical point in the evolution of the field, in a bottom-up approach from the biologist who are suffering severe IT problemes. MuG, supported by European leaders in the field, join three different expertise: biologist with interest in chromatin structure, methods developers and HPC facilities with strong history of supporting Bio-computational problems. We believe that MuG will be a steep-forward in approaching the potential of High Performance Computing to the development of 3D/4D genomics, and will contribute to give a structure to this new and exciting field.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: INFRADEV-3-2015 | Award Amount: 19.05M | Year: 2015

The life sciences are undergoing a transformation. Modern experimental tools study the molecules, reactions, and organisation of life in unprecedented detail. The precipitous drop in costs for high-throughput biology has enabled European research laboratories to produce an ever-increasing amount of data. Life scientists are rapidly generating the most complex and heterogeneous datasets that science can currently imagine, with unprecedented volumes of biological data to manage. Data will only generate long-term value if it is Findable, Accessible, Interoperable and Re-usable (FAIR). This requires a scalable infrastructure that connects local, national and European efforts and provides standards, tools and training for data stewardship. Formally established as a legal entity in January 2014, ELIXIR - the European life science Infrastructure for Biological Information - is a distributed organisation comprising national bioinformatics research infrastructures and the European Bioinformatics Institute (EMBL-EBI). This coordinated infrastructure includes data standards, exchange, interoperability, storage, security and training. Recognising the importance of a data foundation for European life sciences, the ESFRI and European Council named ELIXIR as one of Europes priority Research Infrastructures. In response ELIXIR have developed ELIXIR-EXCELERATE. The project will fast-track ELIXIRs early implementation phase by i) coordinate and enhance existing resources into a world-leading data service for academia and industry, ii) grow bioinformatics capacity and competence across Europe, and iii) complete the management processes needed for a large distributed infrastructure. ELIXIR-EXCELERATE will deliver a step-change in the life sciences. It will enable cost-effective and sustainable management and re-use of data for millions of users across the globe and improve the competitiveness of European life science industries through accessible data and robust standards and tools.

Agency: Cordis | Branch: H2020 | Program: CSA | Phase: SwafS-25-2016 | Award Amount: 642.36K | Year: 2016

The proposed European Academy for Biomedical Science (ENABLE) consortium will connect aspiring European researchers of tomorrow with prominent scientists of today, in particular to inspire and to give them the necessary tools to follow in their footsteps. ENABLE will organize peer-reviewed symposia celebrating European life science achievements from molecule to man/patient. These symposia will have a strong element of public outreach and engagement thereby giving all stakeholders a voice on medical scientific discovery. A new and unique brand of conferences aimed at accelerating life science discovery and personalized medicine. ENABLE scientific symposia: ENABLE will organize an annual scientific symposium, across one of the thematic areas of the partner institutes with the intention of exploring the newest research and pioneering developments. These ENABLE symposia will be organized entirely by a committee of PhD students and postdocs i.e. by and for young researchers, including basic, applied and clinical scientists (in training). ENABLE outreach: ENABLE symposia will actively seek public engagement via outreach activities to the European adult public as well as primary- and high-school children. From rejoicing scientific achievements to public understanding of scientific research, open discussions regarding challenging and ethical topics are paramount, e.g. hype versus hope. These topics will be addressed in specially designed events for the target groups, providing a first European platform for such consultations and knowledge exchange. ENABLing careers: Coupled to the scientific symposium, ENABLE will organize specific career workshops covering essential skills and job opportunities. ENABLing careers will become a hub for promoting open positions for undergraduates and young researchers in European institutions undertaking biomedical and life sciences research.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: EINFRA-5-2015 | Award Amount: 4.78M | Year: 2015

Life Science research has become increasingly digital, and this development is accelerating rapidly. Biomolecular modelling techniques such as homology modelling, docking, and molecular simulation have advanced tremendously due to world-leading European research, resulting in extreme demands for better computational performance and throughput as these tools are used in applied research and industrial development. This research has direct influence on our daily life in areas such as health and medical applications, the development of new drugs, efficient drug delivery, biotechnology, environment, agriculture and food industry. Life Science is one of the largest and fastest growing communities in need of high-end computing, and it is a critically important industrial sector for Europe. However, compared to some other disciplines, the use of e-Infrastructure is still relatively new - many advanced techniques are not applied commercially due to limited experience. It requires significant support to: Make e-Infrastructure useable by researchers who are not computing experts, Improve the performance and applicability of key life science applications, Handle large amounts of data in computational workflows. BioExcel proposes to tackle these challenges by establishing a dedicated CoE for Biomolecular Research, covering structural and functional studies of the building blocks of living organisms - proteins, DNA, saccharides, membranes, solvents and small molecules like drug compounds - all areas where with large academic and industrial users bases in Europe. Specifically, BioExcel will Improve the efficiency and scalability of important software packages for biomolecular research; Improve the usability of ICT technologies for biomolecular researchers in academia and industry; Promote best practices and train end users in making good use of both software and e-Infrastructure; Develop appropriate governance structures and business plans for a sustainable CoE.

Gonzalez C.,Barcelona Institute for Research in Biomedicine | Gonzalez C.,Catalan Institution for Research and Advanced Studies
Nature Reviews Cancer | Year: 2013

For decades, lower-model organisms such as Drosophila melanogaster have often provided the first glimpse into the mechanism of action of human cancer-related proteins, thus making a substantial contribution to elucidating the molecular basis of the disease. More recently, D. melanogaster strains that are engineered to recapitulate key aspects of specific types of human cancer have been paving the way for the future role of this 'workhorse' of biomedical research, helping to further investigate the process of malignancy, and serving as platforms for therapeutic drug discovery.© 2013 Macmillan Publishers Limited. All rights reserved.

Perez A.,Barcelona Institute for Research in Biomedicine
Accounts of chemical research | Year: 2012

It has been known for decades that DNA is extremely flexible and polymorphic, but our knowledge of its accessible conformational space remains limited. Structural data, primarily from X-ray diffraction studies, is sparse in comparison to the manifold configurations possible, and direct experimental examinations of DNA's flexibility still suffer from many limitations. In the face of these shortcomings, molecular dynamics (MD) is now an essential tool in the study of DNA. It affords detailed structural and dynamical insights, which explains its recent transition from a small number of highly specialized laboratories to a large variety of groups dealing with challenging biological problems. MD is now making an irreversible journey to the mainstream of research in biology, with the attendant opportunities and challenges. But given the speed with which MD studies of DNA have spread, the roots remain somewhat shallow: in many cases, there is a lack of deep knowledge about the foundations, strengths, and limits of the technique. In this Account, we discuss how MD has become the most important source of structural and flexibility data on DNA, focusing on advances since 2007 of atomistic MD in the description of DNA under near-physiological conditions and highlighting the possibilities and shortcomings of the technique. The evolution in the field over the past four years is a prelude to the ongoing revolution. The technique has gained in robustness and predictive power, which when coupled with the spectacular improvements in software and hardware has enabled the tackling of systems of increasing complexity. Simulation times of microseconds have now been achieved, with even longer times when specialized hardware is used. As a result, we have seen the first real-time simulation of large conformational transitions, including folding and unfolding of short DNA duplexes. Noteworthy advances have also been made in the study of DNA-ligand interactions, and we predict that a global thermodynamic and kinetic picture of the binding landscape of DNA will become available in a few years. MD will become a crucial tool in areas such as biomolecular engineering and synthetic biology. MD has also been shown to be an excellent source of parameters for mesoscopic models of DNA flexibility. Such models can be refined through atomistic MD simulations on small duplexes and then applied to the study of entire chromosomes. Recent evidence suggests that MD-derived elastic models can successfully predict the position of regulatory regions in DNA and can help advance our understanding of nucleosome positioning and chromatin plasticity. If these results are confirmed, MD simulations can become the ultimate tool to decipher a physical code that can contribute to gene regulation. We are entering the golden age of MD simulations of DNA. Undoubtedly, the expectations are high, but the challenges are also enormous. These include the need for more accurate potential energy functionals and for longer and more complex simulations in more realistic systems. The joint research effort of several groups will be crucial for adapting the technique to the requirements of the coming decade.

Luders J.,Barcelona Institute for Research in Biomedicine
Nature Cell Biology | Year: 2012

The pericentriolar material (PCM), the microtubule-organizing component of the centrosome, contains a multitude of proteins and is commonly described as an amorphous cloud surrounding the centrioles. However, the days of the PCM as an unstructured matrix are numbered. Using super-resolution microscopy, several reports have now revealed remarkable domain organization within the PCM. © 2012 Macmillan Publishers Limited.

Lopez-Domenech G.,Barcelona Institute for Research in Biomedicine
Nature communications | Year: 2012

Brain function requires neuronal activity-dependent energy consumption. Neuronal energy supply is controlled by molecular mechanisms that regulate mitochondrial dynamics, including Kinesin motors and Mitofusins, Miro1-2 and Trak2 proteins. Here we show a new protein family that localizes to the mitochondria and controls mitochondrial dynamics. This family of proteins is encoded by an array of armadillo (Arm) repeat-containing genes located on the X chromosome. The Armcx cluster is unique to Eutherian mammals and evolved from a single ancestor gene (Armc10). We show that these genes are highly expressed in the developing and adult nervous system. Furthermore, we demonstrate that Armcx3 expression levels regulate mitochondrial dynamics and trafficking in neurons, and that Alex3 interacts with the Kinesin/Miro/Trak2 complex in a Ca(2+)-dependent manner. Our data provide evidence of a new Eutherian-specific family of mitochondrial proteins that controls mitochondrial dynamics and indicate that this key process is differentially regulated in the brain of higher vertebrates.

Agency: Cordis | Branch: H2020 | Program: MSCA-IF-EF-ST | Phase: MSCA-IF-2015-EF | Award Amount: 158.12K | Year: 2017

In this project I will use Single Molecule Pull-down (SiMPull) for studying activity and regulation of human gamma-tubulin ring complexes (gamma-TuRCs). Gamma-TuRCs are the main nucleators of microtubule (MT) polymerization. Additionally, gamma-TuRCs may play a role in modulating MT dynamics. Regulation of gamma-TuRC activity is key to organizing the dynamic MT arrays needed for essential processes in various cell types. Progress in understanding gamma-TuRC regulation at the molecular level is currently hampered by a lack of information about subunit stoichiometries and interactions, and by technical difficulties that have prevented reconstitution of gamma-TuRCs in vitro. I will tackle these challenges by using SiMPull to immunoprecipitate and immobilize gamma-TuRCs to a glass surface directly from cell extracts collected at different cell cycle stages, and analyze individual gamma-TuRCs using high resolution microscopy. I will express tagged gamma-TuRC subunits in cells to isolate wildtype and mutant gamma-TuRCs. Using fluorescent protein tags and antibodies I will visualize and quantify components in individual gamma-TuRCs and, by incubation in pure tubulin and GTP, determine how gamma-TuRC composition is related to its ability to nucleate MTs and modulate MT dynamics. Together, the proposed research will expand the fields toolbox, thereby allowing new, molecular level insight into gamma-TuRC activity and its regulation.

Agency: Cordis | Branch: H2020 | Program: ERC-COG | Phase: ERC-CoG-2015 | Award Amount: 2.00M | Year: 2016

Finding the mutations, genes and pathways directly involved in cancer is of paramount importance to understand the mechanisms of tumour development and devise therapeutic strategies to overcome the disease. Due to their role in cancer development and maintenance, the proteins encoded by cancer genes are candidate therapeutic targets. Indeed, in recent years we have witnessed the development of successful cancer-targeting therapies to counteract the effect of driver mutations. Although the coding part of the human genome has now largely been explored in the search for cancer driver mutations in most frequent cancer types, the extent of involvement of noncoding mutations in cancer development remains a mystery. The main challenges faced are: 1) the functional role of most noncoding regions is unknown, and 2) tumours often have thousands of somatic mutations, so that distinguishing cancer driver mutations from bystanders is like finding the proverbial needle in a haystack. To overcome these two challenges I propose to analyse the pattern of somatic mutations across thousands of tumours in noncoding regions to identify signals of positive selection. These signals are an indication that mutations in the region have been positively selected during tumour evolution and are thus directly involved in the tumour phenotype. The large scale analysis proposed here will allow us to create a catalogue of noncoding elements involved in different types of cancer upon mutations. We will study in detail a selected set of driver elements to uncover their specific function and role in the tumourigenic process. Furthermore, we will explore possibilities of counteracting their driver effect with targeted drugs. The results of this project may boost our understanding of the biological role of noncoding regions, help to unravel novel molecular causes of cancer and provide novel targeted therapeutic opportunities for cancer patients.

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