Knowledge lies at the heart of the European Union’s Lisbon Strategy to become the « most dynamic competitive knowledge-based economy in the world». The ‘ knowledge triangle’ - research, education and innovation - is a core factor in European efforts to meet the ambitious Lisbon goals. Numerous programs, initiatives and support measures are carried out at EU level in support of knowledge. The Seventh Framework Program (FP7) bundles all research-related EU initiatives together under a common roof playing a crucial role in reaching the goals of growth, competitiveness and employment; along with a new Competitiveness and Innovation Framework Program (CIP), Education and Training programs, and Structural and Cohesion Funds for regional convergence and competitiveness. It is also a key pillar for the European Research Area (ERA). The broad objectives of FP7 have been grouped into four categories: Cooperation, Ideas, People and Capacities. For each type of objective, there is a specific program corresponding to the main areas of EU research policy. All specific programs work together to promote and encourage the creation of European poles of (scientific) excellence
CENTER-TBI (COOPERATION - ICT - Information and Communication Technologies, 2013-2020)
Collaborative European NeuroTrauma Effectiveness Research in TBI
Traumatic Brain Injury (TBI) is a major cause of death and disability, leading to great personal suffering to victim and relatives, as well as huge direct and indirect costs to society. Strong ethical, medical, social and health economic reasons therefore exist for improving treatment. The CENTER-TBI project will collect a prospective, contemporary, highly granular, observational dataset of 5400 patients, which will be used for better characterization of TBI and for Comparative Effectiveness Research (CER).
The generalisability of our results will be reinforced by a contemporaneous registry level data collection in 15-25,000 patients. Our conceptual approach is to exploit the heterogeneity in biology, care, and outcome of TBI, to discover novel pathophysiology, refine disease characterization, and identify effective clinical interventions. Key elements are the use of emerging technologies (biomarkers, genomics and advanced MR imaging) in large numbers of patients, across the entire course of TBI (from injury to late outcome) and across all severities of injury (mild to severe). Improved characterization with these tools will aid Precision Medicine, a concept recently advocated by the US National Academy of Science, facilitating targeted management for individual patients.
The consortium includes leading experts and will bring outstanding biostatistical and neuroinformatics expertise to the project. Collaborations with external partners, other FP7 consortia, and international links within InTBIR, will greatly augment scientific resources and broaden the global scope of our research. We anticipate that the project could revolutionize our view of TBI, leading to more effective and efficient therapy, thus improving outcome and reducing costs. These outcomes reflect the goals of CER to assist consumers, clinicians, health care purchasers, and policy makers to make informed decisions, and will improve healthcare at both individual and population levels.
A. Maas, Universitair Ziekenhuis Antwerpen, Antwerpen, BELGIUM
S. Laureys, GIGA, University of Liège, Liège, BELGIUM
Charité University Medicine Berlin, Belin, GERMANY
Georg-August-Universität Göttingen, Göttingen, GERMANY
University of Helsinki, Helsinki, FINLAND
Imperial College London, London, UNITED-KINGDOM
Karolinska Institute, Stockholm, SWEDEN
University of Pecs, PRCS, HUNGARY
University of Cambridge, Cambridge, UNITED KINGDON
Universitätsklinikum Heildelberg, Heidelberg, GERMANY
University of Sheffield, Sheffield, UNITED KINGDOM
Teknologian Tutkimuskeskus VTT, Espoo, FINLAND
University of Trnava, SLOVAKIA
Varsinais-Suomen sairaanhoitopiirin kuntayhtymä, Turkü, FINLAND
IcoMetrix NV, Leuven, BELGIUM
Assistance Publique - Hôpitaux de Paris, Paris, FRANCE
Azienda Ospedaliera san Gerardo di Monza, Monza, ITALY
Genome Research Council, London, UNITED KINGDOM
Medical Research Council, Swindon, UNITED KINGDOM
Private Universitaet Witten/Herdecke, Witten, GERMANY
Academisch Ziekenhuis Leiden, Leiden, GERMANY
GABO:milliarium mbH & Co KG, Munchen, GERMANY
Greater Glasgow Health Board, Glasqow, UNITED KINGDOM
The University of Stirling, Stirling, UNITED KINGDOM
Region Hovedstaden, Hillerod, DANEMARK
Oslo Universitetssykehus, Oslo, NORWAY
Oxford Brookes University, Oxford, UNITED KINGDOM
NHS Blood and Transplant (NHSBT), Walford, UNITED KINGDOM
The Regents of the University of California, Oakland, USA
University of Florida, USA
University of Cincinnati, Cincinnati, USA
Monash University, Victoria, AUSTRALIA
Auckland University of Technology, Auckland, NEW ZEALAND
Renji Hospital Shanghai Jiaotong University School of Medicine, Changai, CHINA
Ernst-Moritz-Arndt Universität Greifswald, Geifswald, GERMANY
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico, Milano, ITALY
Internationale Gesellschaft zur Erforschung von Hirntraumata, AUSTRIA
AFHELO (Cooperation-Health, 2012-2015)
Preclinical proof of concept of AF243 potency to prevent and/or treat sensorineural hearing loss
Sensorineural hearing impairment (HI), which constitute the majority of hearing loss, are characterized mostly by damage to the sensory structures (hair cells, HCs) and neurons (type I and II primary auditory neurons) of the auditory portion of the inner ear. Currently, approximately 10% of the global population (40% of people over 65) suffers from HI, and treatment is limited to replacement techniques of auditory function. To address this problem, AFHELO projects plans to evaluate potency of AF243, a small molecule which is a strong inducer of cell differen tiation with interesting potential on carcino-embryonic cells differentiation and neuron survival, and on an in vivo model of chemo-induced deafness, used for cochlear implant testing. The strategy is to optimize AF243 development by first extending the therapeutic applications to two major types of HI (noise induced and age related/presbycusis) and second by completing the preclinical studies (pharmacology, mechanism of action, ADME, safety) supporting the clinical evaluation of AF243 for prevention and/or treatment of sensorineural HI. The objective of the AFHELO project is to complete and optimize the preclinical development of AF243, second lead drug candidate of Affichem and to extend its field of therapeutic action in the two main types of hearing loss related to age and noise.
S. Sivente; AFFICHEM sa, Toulouse, FRANCE (Coordination)
B. Malgrange, GIGA-Neurosciences, Liègen, BELGIUM
Consejo Superior de Investigaciones Cientificas, Madrid, SPAIN
TUMORLYMPHAINHIBIT (PEOPLE - IEF - Intra-European Fellowships, 2014-2016)
Identification, characterization and mechanisms of action of new tumor-associated lymphangiogenesis inhibitors
Cancer and tumor metastasis is the largest single cause of death in both, men and women, claiming over 7 million lives each year worldwide and, it is expected that by 2020 the number of dead cancer patients will grow to 10 million per year. Metastatic tumor cells utilize blood and lymphatic vessels as routes for dissemination and it is well known that lymphatic vasculature serves as a major route for tumor metastasis. Besides, lymphangiogenesis, the new lymphatic vessels formation from pre-existing ones, is pivotal for cancer cells spreading from primary sites to lymph nodes and, further, to distant tissues. Consequently, the search and identification of new tumor-induced lymphangiogenesis inhibitors and the understanding of their mechanisms of action, are a hot topic in the field of pharmacological research. In the present project, the applicant will finished the characterization of two marine compounds, toluquinol and AD0157, started during a short stay in the host institute. Preliminary results have shown that both compounds have excellent antilymphangiogenic properties in in vitro and ex vivo assays and, in the course of the present project they will be tested in in vivo models and their molecular targets will be revealed. Furthermore, other two new marine compounds will be analyzed in in vitro, ex vivo and in vivo experimental approaches. In these studies the applicant will focus in the behavior of the lymphatic endothelial tip and stalk cells, in order to shed light on their morphological and biochemical features. Hence, this project will increase significantly the acquisition of innovative knowledge on lymphangiogenesis phenomenon, on the different lymphatic endothelial tip/stalk cells features and on the cellular and molecular mechanisms of action of some natural compounds to inhibit tumor-related lymphangiogenesis. Those compounds with excellent antilymphangiogenic properties will be patented in order to be commercially exploitable as antitumor drugs.
Prof. A. Noel, GIGA-Cancer, University of Liège, BELGIUM
Trans_CEDAR (PEOPLE - IEF - Intra-European Fellowships, 2014-2016)
Identifying Inflammatory Bowel Disease causative genes through trans-eQTLs mapping within GWAS loci
"Life-time prevalence of inflammatory bowel disease (IBD) is reaching an alarming rate of > 1/400 in industrialized societies. Improved understanding of disease pathogenesis is essential to develop more effective preventive, diagnostic and therapeutic measures. Genome-wide association studies (GWAS) have identified ~ 160 risk loci contributing to inherited predisposition to Crohn's disease and/or ulcerative colitis. While this has already led to the identification of new perturbed pathways and potential drug targets, causative genes and variants remain unknown for the vast majority of risk loci. Moreover, the identified risk loci only account for an estimated 25% of inherited risk. GWAS loci are likely to be regulatory and therefore alter expression levels of other genes. In the present project we propose to apply an integrated genomic and transcriptomic approach to identify novel genes and pathways that are causally involved in inherited prediposition to IBD. We aim to detect causative genes implicated in IBD’s susceptibility through the evaluation of trans-eQTLs within GWAS loci. Trans_CEDAR is based on the generation of an integrated dataset of nine cell/tissue types collected on 350 healthy caucasians individuals, as well as on the use of next generation sequencing to identify rare variants in functionally-incriminated candidate genes. We expect to detect new causative variants that may constitute new drug targets. The present project will also generate a map of trans-eQTL in different tissues, equally useful for the study of other diseases, to be shared with the scientific community."
Prof. M. Georges, GIGA-Genetics, University of Liège, BELGIUM
ChIP Seq RA CD (PEOPLE - IOF - International Outgoing Fellowships, 2012-2015)
Identification of regulator variants in Rheumatoid Arthritis and Crohn's Disease
Genome-wide association studies (GWAS) extensively used to identify genetic risk variant in human disease such as Crohn’s disease (CD) and Rheumatoid Arthritis (RA) have found dozens of risk allele in aggregate explaining ~ 10-15% of heritability. However the molecular mechanisms that underlie these associations remain elusive. The major reason is that only a small fraction of trait-associated variants can be linked to coding sequences. It was speculated that many of the underlying causal alleles impact regulatory elements (such as promoter or enhancer) controlling the expression of proximal or distal genes. The identification of regulatory elements influenced by risk variant involves assaying epigenetic chromatin marks, which correspond to chemical modifications of histone altering the chromatin structure to allow access for transcriptional machinery. A practical challenge is that there hundred of chromatin marks might potentially be assayed, and that it is prohibitive to conduct studies on all of them in large numbers of different tissues or in samples collected from many individuals. However, because chromatin marks provide a redundant information the status of a small subset of the most informative marks might be characterized, allowing for more focused assays in tissue libraries and populations to link variants to regulatory mechanisms. Additionally, it is challenging for a given phenotype to know which cell type(s) are most useful to assay chromatin marks in order to fine map risk alleles. Furthermore if the critical cell types were known, it might possible to develop cell specific functional experiment to identify genes impacted by these risk variants.
The objectives of this project are/were:
* To develop an approach to identify the keys pathogenic cells type impacted by risk variants and to apply this approach in the context of RA and CD.
* To identify the most informative chromatin marks, to track the cell-specificity of risk variant in order to develop chromatin assays on large tissues/cell type library.
* To identify the regulatory elements impacted by risk variants and by which mechanisms they are affected.
* To develop an approach to identify the genes impacted by risk variants and to apply this approach in the context of RA and CD.
* To develop a new research niche area aiming to develop approaches integrating different available genomic data-source to understand the biological role risk variant discovered through of genetics studies.
* Develop a new research group in Europe in the functional genomic research field.
Prof. M. Georges, GIGA-Genetics, University of Liège, BELGIUM
MastCellsInEczema (PEOPLE - IOF - International Outgoing Fellowships, 2012-2015)
Mast cells in eczema - Study of the role of mast cells in the modulation of immune and inflammatory responses associated with eczema : novel genetic approaches from mouse
"The overall objective of this grant is to complement Dr. Marichal’s expertise in basic and translational Allergy and Immunology. He will therefore integrate an outstanding laboratory in this area (Pr. Stephen J. Galli’s laboratory) at Stanford University School of Medicine, a world leader in medical education, training and research. Scientifically, Dr. Marichal will acquire cutting-edge knowledge in the detailed mechanistic understanding of allergic disorders, which are increasingly recognized as a major global public health problem. Indeed, the current proposal aims to evaluate in depth the contribution of mast cells in early immune and late inflammatory responses associated with skin eczema, the most complex allergic skin disorder. To address this question, two complementary genetic approaches of mast-cell deficient mice will be used in combination with a clinically relevant mouse model of skin eczema. In addition, Dr. Marichal will learn and take advantage of the innovative tool of Gene Set Enrichment Analysis to assess to relevance of the findings to the human disease. This challenging project is possible thanks to Dr. Marichal’s previous experience, in combination with the financial and technical resources of the host laboratory, as well as the scientific and training environment that will be provided. Pr. Galli has indeed a long history of highly successful training of postdoctoral researchers. Moreover, Dr. Marichal will benefit from many training and educational programs, enabling him to gain essential skills at the level of leadership, project management and financial independency and helping him in growing as an independent researcher. Finally, it is the goal of the outgoing and return host laboratories to create a strong international collaboration and a worldwide network of experts in the fields covered by the project, thereby addressing societal challenges and training needs at the worldwide scale."
Prof. F. Bureau, GIGA-Infection, Immunity, Inflammation, University of Liège, BELGIUM
eTime (PEOPLE - IRSES - International Research Staff Exchange Scheme, 2013-2016)
Engineering Technology-based Innovation in Medicine
"Background: Healthcare systems worldwide are increasingly unable to meet growing demand for and cost of healthcare. Changing demographics leading to increasing demand for services of increasing cost exacerbate this problem. Thus,healthcare costs are an increasingly unaffordable share of economically constrained national budgets.
More specifically, an average 10% of healthcare costs are for acute and intensive care, which equates ~1% of GDP in many EU countries – a significant share. Highly trained doctors and nurses are the scarce and costly resource in critical and acute care. Thus,improving care and productivity in intensive and acute care units by merging engineering, technology and medicine presents a significant research and economic opportunity and challenge.
The Specific Problem: While acute and critical care doctors have a range of technology and sensors at their disposal, their ability to rapidly provide the more consistent, patient-specific care required to improve productivity and patient outcomes is limited. In particular, they are unable to take full advantage of the wealth of data they are presented to best utilise the pumps,ventilators and other technologies used to provide care.
The Solution: The application of clinically validated computer models of patient physiology that can be made patient-specific using data at their bedside can integrate this patient data into a clear physiological picture of patient-specific condition and response to treatment, as well as help guide therapy. These computer models can be combined with automation technology to improve both the productivity and quality of care, alleviating demand on scarce and costly personnel.
Proposed Answer: Model-based Therapeutics (MBT) is an emerging field combining computer models of human physiology, clinical data and automation of care to create innovative solutions to major clinical problems. This project will create an international MBT consortium centered on 3 major core projects."
B. Benyó, Budapesti Muszaki Es Gazdasagtudomanyi Egyetem, Budapest, HUNGARY (Coordination)
T. Desaive, GIGA-Cardiovascular Sciences, BELGIUM
K.Moeller, Hochschule Furtwangen University, Furtwangen, GERMANY
Bone-Net (PEOPLE - ITN - Initial Training Network, 2011-2015)
European Training Network on Cancer Induced Bone Diseases
"Several cancers are prone to metastasize to bone. Combating bone metastasis, especially the early dissemination of cancer cells in bone, requires basic research knowledge, skills in different technologies and longstanding clinical experience in order to make clinically significant progress. BONE-NET is a european consortium with complementary expertises in the fields of cancer and bone. It brings together 6 leading academic groups and 3 SMEs. BONE-NET’s scientific project will aim at investigating the early molecular mechanisms of metastases associated with breast and prostate cancers and primary bone cancers (e.g., osteosarcomas), including the identification of new genes and their regulators (microRNAs) that draw cancer cells to colonize bone and let these cells adapt and thrive in the bone marrow. This network will then seek to identify and develop molecularly-targeted therapies. BONE-NET’s primary objective will be to train 11 early-stage (ESR) and 3 experienced (ER) researchers in technical skills such as genomics, proteomics, advanced microscopical methods, animal experimentation, noninvasive in vivo imaging methodologies and drug development. None of the participating laboratories use all of these approaches, but through workshops, courses and secondments ESR/ER will become expert in many of these disciplines. The network additional objective will be to foster collaborations between participating laboratories, in which ESR/ER will take part through individual training-through-research projects. The training programme will also expose the ESR/ER to the industry which will offer courses and a set of complementary skills (ethics, intellectual property rights, entrepreneurship), thereby enabling them to gain industrial work experience. Overall, at the end of the project, ESR/ER will have acquired enough skills in order to manage their own research programmes and to envisage attractive career perspectives within Europe."
J. Olaiz, Université Lyon 1 Claude Bernard, Villeurbane, FRANCE (Coordination)
A. Bellahcene, GIGA-Cancer, Université de Liège, BELGIUM
V. Castronovo, GIGA-Cancer, Université de Liège, BELGIUM
DNA Vision sa, BELGIUM
Leiden University Medical Centre, THE NETHERLANDS
Med-Discovery SA, SWITZERLAND
Université de Nantes, Nantes, FRANCE
University of Aberdeen, Aberdeen, UNUTED KINGDOM
University of Eastern Finland, FINLAND
MLPM2012 (PEOPLE - ITN - Initial Training Network, 2013-2016)
Machine Learning for Personalized Medicine
"Over the last decade, enormous progress has been made on recording the health state of an individual patient down to the molecular level of gene activity and genomic information – even sequencing a patient’s genome for less than 1000 dollars is no longer an unrealistic goal. However, the ultimate hope to use all this information for personalized medicine, that is to tailor medical treatment to the needs of an individual, remains largely unfulfilled.
To turn the vision of personalized medicine into reality, many methodological problems remain to be solved: there is a lack of methods that allow us to gain a causal understanding of the underlying disease mechanisms, including gene-gene and gene-environment interactions. Similarly, there is an urgent need for integration of the heterogeneous patient data currently available, for improved and robust biomarker discovery for disease diagnosis, prognosis and therapy outcome prediction.
The field of machine learning, which tries to detect patterns, rules and statistical dependencies in large datasets, has also witnessed dramatic progress over the last decade and has had a profound impact on the Internet. Amongst others, advanced methods for high-dimensional feature selection, causality inference, and data integration have been developed or are topics of current research. These techniques address many of the key methodological challenges that personalized medicine faces today and keep it from rising to the next level.
Despite this rich potential of machine learning in personalized medicine, its impact on data-driven medicine remains low, due to a lack of experts with knowledge in both machine learning and in statistical genetics. Our ITN aims to close this gap by bringing together leading European research institutes in Machine Learning and Statistical Genetics, both from the private and public sector, to train 14 early stage researchers."
Max Planck Gesellschaft zur Foerderung der Wissenchaften e.v., München, GERMANY (Coordination)
K. Van Steen, GIGA-Systems Biology, Université de Liège, BELGIUM
Assoc. pour la recherche et de Dévelpt des méthodes et processus industriels, FRANCE
University of Sheffield, UNITED KINGDOM
INSERM, Paris, FRANCE
Crosslinks B.V., Rotterdam, THE NETHERLANDS
Siemens AG, München, GERMANY
Nhumi Technologies AG, München, GERMANY
Pharmatics Limited, Edinburg, UNITED KINGDOM
Universidad Carlos III de Madrid, Madrid, SPAIN
Fund. de la comunidad valenciana centro de investigacion Principe Felipe, Valencia, SPAIN
Sloan-Kettering Institute for Cancer Research Corporation, New York, USA
- GIGA-Cardiovascular Sciences
- GIGA-CRC In vivo Imaging
- GIGA-In silico Medicine
- GIGA-Inflammation, Infection & Immunity
- GIGA-Medical Genetics
- GIGA-Molecular Biology of Diseases
- Projets Européens
- Projets d'excellence
- Recherche translationnelle
- Vulgarisation scientifique