COST ACTION
Titulo: COST Action BM1204 EU Pancreas: An integrated European platform for pancreas cancer research: from basic science to clinical and public health interventions for a rare disease
Referencia: BM1204
Investigador Principal: Malats Riera, Nuria
Fecha Inicio: 01/04/2013
Fecha Fin: 13/12/2016
Presupuesto Otorgado: 300.283,80€
Fuente de Financiación: 7 FRAMEWORK PROGRAMME ( 2007-2013 )
Resumen
The application of the rapidly evolving -omics technologies to cancer research is a reality and it has demonstrated that large-scale international collaboration is essential to decipher relevant information in the context of massive-scale interrogations. This is even more important for rare and dreadful diseases like pancreas cancer (PDAC). We propose the creation of a unique European platform to facilitate the collaboration of a broad range of European and international PDAC multidisciplinary research groups to integrate knowledge and experience in a multidisciplinary way “from cell to society
EURATOM
Titulo: RISK-IR: Risk, Stem Cells and Tissue Kinetics – Ionising Radiation
Referencia: 323267
Investigador Principal: Serrano Marugán, Manuel
Fecha Inicio: 30/04/2017
Fecha Fin: 31/12/2018
Presupuesto Otorgado: 6.685.000,00€
Fuente de Financiación: 7 FRAMEWORK PROGRAMME ( 2007-2013 )
Resumen
The magnitude of cancer risk in humans exposed to low radiation doses (menos 100mSv) is uncertain and depends upon extrapolation of human population based estimates obtained at higher doses. The linear non-threshold extrapolation model currently used has some support from mechanistic/biophysical considerations but it is not based on understanding of the biological responses of the cells of origin for radiation cancer. Stem cells are widely recognised as the cells of origin for many cancers. Understanding the responses of stem cells to low radiation doses will be important therefore in providing mechanistic support for low dose cancer risk extrapolation. In this project, techniques emerging from stem cell biological and tissue kinetics research will be used to address several major areas of uncertainty in low dose (menos 100 mGy) cancer risk estimates:
- The identification and enumeration of stem/progenitor cells at risk
- Understanding low dose radio-sensitivity of stem cells and tissues.
- Improving understanding of mechanisms of age-dependant cancer risk
- Improving understanding of tissue specific differences in cancer risk.
- Identification of key events and individual susceptibility factors associated with cancer development.
The primary output of the RISK-IR project will be peer reviewed scientific papers. Considerable efforts will be made to consolidate scientific evidence of relevance for radiation protection through reviews and dissemination of project results and implications to radiation protection specialists will be facilitated through a stakeholder meeting in the final year of the project.
INNOVATIVE MEDICINES INITIATIVE JOINT UNDERTAKING (IMI JU)
Titulo: e-TOX: Integrating bioinformatics and chemoinformatics approaches for the development of expert systems allowing the in silico prediction of toxicities
Referencia: 115002
Investigador Principal: Valencia Herrera, Alfonso
Fecha Inicio: 01/01/2010
Fecha Fin: 31/12/2016
Presupuesto Otorgado: 6.910.018,00€
Fuente de Financiación: 7 FRAMEWORK PROGRAMME ( 2007-2013 )
Resumen
The eTOX consortium proposes to develop innovative methodological strategies and novel software tools to better predict the toxicological profiles of new molecular entities in early stages of the drug development pipeline. This will be achieved by coordinating the efforts of specialists from academia and SMEs in the wide scope of disciplines that are required to move towards a more reliable modelling of the complex relationships existing
between molecular and in vitro information and the in vivo toxicity outcomes of drugs. The proposed strategy includes a synergetic integration of innovative approaches in the following areas:
Database building and management, including masking procedures for sensitive data, with the aim of facilitating the sharing of information among pharmaceutical companies.
- Ontologies and text mining techniques, with the purpose of facilitating knowledge extraction from legacy preclinical reports and biomedical literature.
- Chemistry and structure-based approaches for the molecular description of the compounds considered, as well as of the biological anti-targets responsible for the secondary pharmacologies.
- Prediction of absorption and metabolism since these ADME properties are often critically related to toxicological events.
- Computational genomics to afford the inter-species and inter-individual variabilities that complicate the interpretation of experimental and clinical outcomes.
- Systems biology approaches in order to cope with the complex biological mechanisms which govern in vivo safety problems.
- Sophisticated statistical analysis tools required to derive the inevitably highly-multivariate QSAR models. D
- evelopment and validation (according to the OECD principles) of QSARs, integrative models, expert systems and meta-tools.
- Linkage of toxicity preclinical data with human outcomes
INNOVATIVE MEDICINES INITIATIVE JOINT UNDERTAKING (IMI JU)
Titulo: Open PHACTS: The Open Pharmacological Concepts Triple Store
Referencia: 115191-2
Investigador Principal:Valencia Herrera, Alfonso
Fecha Inicio: 01/03/2011
Fecha Fin: 29/02/2016
Presupuesto Otorgado: 9.988.867,00€
Fuente de Financiación:WHRI-ACADEMY PROGRAMME. 7 FRAMEWORK PROGRAMME ( 2007-2013 )
Resumen
Drug discovery is data-hungry and all major pharmaceutical companies maintain extensive in-house instances of public data alongside internal. Analysis and hypothesis generation for drug-discovery projects requires assembly, overlay and comparison of data from many sources, requiring shared identifiers and common semantics. Expression profiles need to be overlaid with gene or pathway identifiers and reports on compound pharmacology. Alignment and integration of internal and public data and information sources is a significant effort and the process is repeated across companies, institutes and academic laboratories. This represents a significant waste and an opportunity cost. To address these challenges, the OpenPHACTS project will develop open access innovation platform, Open Pharmacological Space (OPS), via a semantic web approach. OPS will comprise data, vocabularies and infrastructure needed to accelerate drug-oriented research. This semantic integration hub will remove key bottlenecks in small molecule drug discovery: disparate information sources, lack of standards and common identifiers, guided by well defined research questions from drug discovery. Workflows for data capture, processing, interoperability, visualization, and chemogenomics will be developed creating a comprehensive Systems Chemical Biology Analysis Network. Security issues around proprietary data, shared via the nanopublication system and accessible for safe querying and reasoning will be properly addressed with expert trusted parties. The OpenPHACTS consortium comprises 14 European academic and SME partners, with leading experts in the fields of data mining, annotation, small molecule data storage and manipulation, target bioinformatics, RDF information handling, massive in silico reasoning and chemical biology. The 8 EFPIA members of OpenPHACTS will contribute drug discovery expertise, data sets, software engineering and programming capacity to the project.
INTEGRATED PROJECT (IP)
Titulo: ASSET: Analysing and Striking the Sensitivities of Embryonal Tumours
Referencia: 259348
Fecha Inicio: 01/11/2010
Fecha Fin: 30/04/2016
Presupuesto Otorgado: 11.999.156,20€
Fuente de Financiación: DEMY PROGRAMME. 7 FRAMEWORK PROGRAMME ( 2007-2013 )
Resumen
Cancer is hallmarked by multiple genetic aberrations that lead to a functional derangement of cellular signalling networks. Embryonal tumours (ETs) comprising neuroblastoma, medulloblastoma and Ewing sarcoma, occur early in life, and thus may reveal pathogenetically relevant lesions clearer than adulthood tumours which carry passenger mutations accumulated during life. ASSET will exploit this fact by focussing on unravelling the signalling networks and their alterations in ETs. The basic hypothesis is that ETs share common pathogenetic principles that can be captured and made accessible to rational analysis by combining high-throughput and high content analysis of the genome, transcriptome and proteome with mathematical modelling. ASSET builds on a previous FP6 consortium, the European Embryonal Tumour Pipeline (EEPT), which generated high-throughput genomic and transcriptomic data on ETs. ASSET is the next logical step to add crucial functional information that will allow us to generate (i) defined in vitro and in vivo tumour systems; (ii) combined analysis of genomic mutations, transcriptome, miRNA expression and dynamic proteome changes; (iii) systematic perturbations; (iv) mathematical modelling to elucidate pathogenetic networks and their emergent behaviour; (v) the virtuous cycle of model validation in relevant biological model systems and clinical samples towards a major goal. This goal is to identify mechanistically understood network vulnerabilities that can be exploited for new approaches to the diagnosis and treatment of major paediatric tumours. Elucidating such core mechanisms will (i) improve understanding of and therapeutic options for these devastating childhood malignancies and (ii) enable a rational approach to deal with the complexity of the pathogenesis of adulthood cancers.
INTEGRATED PROJECT (IP)
Titulo: BLUEPRINT: A BLUEPRINT of Haematopoietic Epigenomes
Referencia: 282510
Fecha Inicio: 01/10/2011
Fecha Fin: 30/09/2016
Presupuesto Otorgado: 29.996.664,00€
Fuente de Financiación:7 FRAMEWORK PROGRAMME ( 2007-2013 )
Resumen
In response to the call for a high impact initiative on the human epigenome, the BLUEPRINT Consortium has been formed with the aim of generating at least 100 reference epigenomes and studying them to advance and exploit knowledge of the underlying biological processes and mechanisms in health and disease. BLUEPRINT will focus on distinct types of haematopoietic cells from healthy individuals and on their malignant leukaemic counterparts. Reference epigenomes will be generated by state-of-the-art technologies from highly purified cells for a comprehensive set of epigenetic marks in accordance with quality standards set by IHEC. This resource-generating activity will be conducted at dedicated centres to be complemented by confederated hypothesis-driven research into blood-based diseases, including common leukaemias and autoimmune disease (T1D), by epigenetic targets and compound identification, and by discovery and validation of epigenetic markers for diagnostic use. By focussing on 100 samples of known genetic variation BLUEPRINT will complete an epigenome-wide association study, maximizing the biomedical relevance of the reference epigenomes. Key to the success of BLUEPRINT will be the integration with other data sources (i.e. ICGC, 1000 genomes and ENCODE), comprehensive bioinformatic analysis, and user-friendly dissemination to the wider scientific community. The involvement of innovative companies will energize epigenomic research in the private sector by creating new targets for compounds and the development of smart technologies for better diagnostic tests. BLUEPRINT will outreach through a network of associated members and form critical alliances with leading networks in genomics and epigenomics within Europe and worldwide. Through its interdisciplinarity and scientific excellence combined with its strong commitment to networking, training and communication BLUEPRINT strives to become the cornerstone of the EU contribution to IHEC.
INTEGRATED PROJECT (IP)
Titulo: RD-CONNECT: An integrated platform connecting registries, biobanks and clinical bioinformatics for rare disease research
Referencia: 305444
Fecha Inicio: 02/11/2012
Fecha Fin: 31/05/2017
Presupuesto Otorgado: 11.997.111,00€
Fuente de Financiación:7 FRAMEWORK PROGRAMME ( 2007-2013 )
Resumen
Despite examples of excellent practice, rare disease (RD) research is still mainly fragmented by data and disease types. Individual efforts have little interoperability and almost no systematic connection between detailed clinical and genetic information, biomaterial availability or research/trial datasets. By developing robust mechanisms and standards for linking and exploiting these data, RD-Connect will develop a critical mass for harmonisation and provide a strong impetus for a global “trial-ready” infrastructure ready to support the IRDiRC goals for diagnostics and therapies for RD in close collaboration with the successful A/B projects. It will build on and transform the current state-of-the-art across databases, registries, biobanks, bioinformatics, and ethical considerations to develop a quality-assured and comprehensive integrated hub/platform in which complete clinical profiles are combined with -omics data and sample availability for RD research. The integrated, user-friendly RD-Connect platform, built on efficient informatics concepts already implemented in international research infrastructures for large-scale data management, will provide access to federated databases/registries, biobank catalogues, harmonised -omics profiles, and cutting-edge bioinformatics tools for data analysis. All patient data types will be linked via the generation of a unique identifier (“RD-ID”) developed jointly with the US NIH. The RD-Connect platform will be one of the primary enablers of progress in IRDiRC-funded research and will facilitate gene discovery, diagnosis and therapy development. RD-Connect has the RD field at its heart and brings together partners with a strong track record in RD research (gene discovery and development of innovative treatments), as well as committed IRDiRC funding partners and representatives of all major international RD initiatives (EU/US/AU/JP) spanning patient organisations, research and public health, to maximise impact to RD patients.
NETWORKS OF EXCELLENCE (NOE)
Titulo: EUROCANPLATFORM: A European Platform for Translational Cancer Research
Referencia: 260791
Fecha Inicio: 01/01/2011
Fecha Fin: 31/12/2016
Presupuesto Otorgado: 11.998.454,00€
Fuente de Financiación:7 FRAMEWORK PROGRAMME ( 2007-2013 )
Resumen
Europe has a number of advantages as regards developing translational cancer research, yet there is no clear European strategy to meet the increasing burden posed by cancer. The FP6 Eurocan+Plus project analysed the barriers underlying the increasing fragmentation of cancer research and stressed the need to improve collaboration between basic/preclinical and comprehensive cancer centres (CCCs), institutions in which care and prevention is integrated with research and education. Furthermore, it proposed the creation of a platform of interlinked cancer centres with shared infrastructures and collaborative projects to facilitate rapid advances in knowledge, and their translation into better cancer care.
In response to these challenges and in line with the call, EurocanPlatform will work towards the goal of decreasing cancer mortality by dealing with three main areas of strategic research: prevention, early detection and improved treatments. It will build the necessary resources and know-how for the entire research continuum: basic research, early and late translational research, clinical research, epidemiological research, implementation in care and population based outcome research. There will be a strong focus on discovery-driven translational cancer research in five selected tumours: breast, head-neck, lung, malignant melanoma and pancreatic cancer. Joint structures and programmes for early detection will contribute to optimal treatment, and novel prevention research programmes will integrate prevention activities in clinical cancer centres as well as public prevention. Collaborations will also include molecular pathway-driven clinical research supported by joint structures for omics, biobanking and biomarker validation to support clinical trials aimed at enhancing patient benefits by individualised treatments.
EurocanPlatform is unique in its nature and represents a commitment from cancer centres to join forces and resources in order to fight cancer.
RESEARCH INFRASTRUCTURES, INCLUDING E-INFRASTRUCTURES (EINFRA)
Titulo: OpenMinTeD: Open Mining INfrastructure for TExt and Data
Referencia: 654021
Fecha Inicio: 01/06/2015
Fecha Fin: 30/06/2017
Presupuesto Otorgado: 5.375.535,50€
Fuente de Financiación:HORIZON 2020 ( 2014-2020 )
Resumen
Recent years witness an upsurge in the quantities of digital research data, offering new insights and opportunities for improved understanding. Text and data mining is emerging as a powerful tool for harnessing the power of structured and unstructured content and data, by analysing them at multiple levels and in several dimensions to discover hidden and new knowledge. However, text mining solutions are not easy to discover and use, nor are they easily combinable by end users. OpenMinTeD aspires to enable the creation of an infrastructure that fosters and facilitates the use of text mining technologies in the scientific publications world, builds on existing text mining tools and platforms, and renders them discoverable and interoperablethrough appropriate registriesand a standards-based interoperability layer, respectively. It supports training of text mining users and developers alike and demonstrates the merits of the approach through several use cases identified by scholars and experts from different scientific areas, ranging from generic scholarly communication to literaturerelated tolife sciences, food and agriculture, and social sciences and humanities. Through its infrastructural activities, OpenMinTeD’s vision is tomake operational a virtuous cycle in which a) primary content is accessed through standardised interfaces and access rules b) by well-documented and easily discoverable text mining services that process, analyse, and annotate text c) to identify patterns and extract new meaningful actionable knowledge, which will be used d) for structuring, indexing, and searching content and, in tandem, e) acting as new knowledge useful to draw new relations between content items and firing a new mining cycle. To achieve its goals, OpenMinTeD brings together different stakeholders, content providers and scientific communities, text mining and infrastructure builders, legal experts, data and computing centres, industrial players, and SMEs.
RESEARCH INFRASTRUCTURES, INCLUDING E-INFRASTRUCTURES (EINFRA)
Titulo: ELIXIR-EXCELERATE: Fast-track ELIXIR implementation and drive early user exploitation across the life-sciences.
Referencia: 676559
Fecha Inicio: 01/09/2015
Fecha Fin: 31/03/2017
Presupuesto Otorgado: 19.051.482,00€
Fuente de Financiación:HORIZON 2020 ( 2014-2020 )
Resumen
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 Europe’s priority Research Infrastructures. In response ELIXIR have developed ELIXIR-EXCELERATE. The project will fast-track ELIXIR’s 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.
SMALL OR MEDIUM-SCALE FOCUSED RESEARCH PROJECTS (STREP)
Titulo: TransBioBC: Translation of novel Biomarkers for Bladder Cancer for clinical outcome prediction
Referencia: 601933
Fecha Inicio: 01/09/2013
Fecha Fin: 29/09/2016
Presupuesto Otorgado: 3.260.358,60€
Fuente de Financiación: 7 FRAMEWORK PROGRAMME ( 2007-2013 )
Resumen
Currently, clinical diagnosis and monitoring of bladder cancer (BC) relies on invasive, highly costly cystoscopy. Additionally, due to high recurrence rates BC treatment is associated with frequent follow-up of patients, making BC one of the most costly types of cancer in terms of management cost. Thus there is a clear clinical need for the development of new approaches for early detection of recurrence and progression.
Our proposal is based on the identification of novel biomarkers (BM) for BC recurrence and progression in urine and powerful technological platforms as extensive foreground work of the involved partners in the framework of FP7 EU projects DECanBio and GENINCA. The objective of TransBioBC is to translate this foreground work in the field of BC and to specifically employ the involved technologies (CE-MS and micro-ELISA), represented by the participating SMEs, for the development of non-invasive urine tests for routine monitoring of BC recurrence and progression. Our project uniquely integrates leading BC clinical experts with experts on proteome analysis and high throughput immunoassay development in an implementation-oriented workflow. Strict monitoring of assay analytical performance, and properly collected and well characterized clinical samples from existing sufficiently powered BC cohorts are combined with in-depth knowledge of regulatory requirements, analysis approaches to define added value and well designed business plans including multi-stakeholder dissemination and exploitation plans.
Collectively, TransBioBC will provide strong evidence for utility of the new BM directly in BC clinical management and as a secondary aim for usage in clinical trials and drug development.
SOCIETAL CHALLENGE 1: HEALTH, DEMOGRAPHIC CHANGE AND WELLBEING (PHC)
Titulo: BRIDGES: Breast Cancer Risk after Diagnostic Gene Sequencing (BRIDGES)
Referencia: 634935
Fecha Inicio: 01/09/2015
Fecha Fin: 31/08/2020
Presupuesto Otorgado: 6.200.000,00€
Fuente de Financiación: HORIZON 2020 ( 2014-2020 )
Resumen
Breast cancer affects more than 360,000 women per year in the EU and causes more than 90,000 deaths. Identification of women at high risk of the disease can lead to disease prevention through intensive screening, chemoprevention or prophylactic surgery. Breast cancer risk is determined by a combination of genetic and lifestyle risk factors. The advent of next generation sequencing has opened up the opportunity for testing in many disease genes, and diagnostic gene panel testing is being introduced in many EU countries. However, the cancer risks associated with most variants in most genes are unknown. This leads to a major problem in appropriate counselling and management of women undergoing panel testing.
In this project, we aim to build a knowledge base that will allow identification of women at high-risk of breast cancer, in particular through comprehensive evaluation of DNA variants in known and suspected breast cancer genes. We will exploit the huge resources established through the Breast Cancer Association Consortium (BCAC) and ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles). We will expand the existing datasets by sequencing all known breast cancer susceptibility genes in 20,000 breast cancer cases and 20,000 controls from population-based studies, and 10,000 cases from multiple case families. Sequence data will be integrated with in-silico and functional data, with data on other known risk factors, to generate a comprehensive risk model that can provide personalised risk estimates. We will develop online tools to aid the interpretation of gene variants and provide risk estimates in a user-friendly format, to help genetic counsellors and patients worldwide to make informed clinical decisions. We will evaluate the acceptability and utility of comprehensive gene panel testing in the clinical genetics context.
SOCIETAL CHALLENGE 5: CLIMATE ACTION, ENVIRONMENT, RESOURCE EFFICIENCY AND RAW MATERIALS (NMP)
Titulo: NoCanTher: Nanomedicine upscaling for early clinical phases of multimodal cancer therapy
Referencia: 685795
Fecha Inicio: 01/04/2016
Fecha Fin: 30/04/2017
Presupuesto Otorgado: 7.113.778,75€
Fuente de Financiación: HORIZON 2020 ( 2014-2020 )
Resumen
During the last four years the Multifun Consortium (FP7 project Nº. 262943) has developed and validated distinct nanoformulations as therapeutic approach against pancreatic and breast cancer. These nanoformulations are based on magnetic iron oxide nanoparticles (MNP) multifuntionalised with a target peptide and an anticancer chemical drug, allowing for a synergistic therapeutic effect produced by the combination of intracellular drug delivery and magnetic hyperthermia. In particular, some of the designed formulations (patent filed PCT/EP2015/056631) have proven their efficacy, safety and non-toxicicty, in in vitro and in vivo studies, against the mentioned cancers, thus making them promising candidates to produce a novel nanomedicine therapy for cancer.
NoCanTher aims at translating one of these nanoformulations to early clinical development for pancreatic cancer. To successfully reach this objective, we will concentrate our efforts in two main group of activities:
- Nanomedicine up-scaling under GMP conditions: NoCanTher will scale up the manufacturing of the proposed nanoformulation from milligram-scale laboratory synthesis up to multigram-scale production to generate sufficient material for clinical and regulatory assays. To this aim, a GMP production line will be optimised and the relevant quality control will be conducted at the different stages of the up-scaling process.
- Clinical trial: NoCanTher will include late preclinical parameter testing to raise a clinical treatment protocol, regulatory assays, as well as the design of the clinical trial and the preparation of the Investigational Medicinal Product Dossier (IMPD).
This strategy will allow us to apply for Clinical Trial Authorisation (CTA) then, we will carry out a Phase I clinical trial.
NoCanTher involves the participation of institutions from three different sectors (academia, industry, clinical) and from five different countries (Ireland, France, Germany, Spain and the UK).