Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Sustaining access to Tissues and data frOm Radiobiological Experiments (STORE)

Framework: FP7 — Euratom
Programme: Nuclear fission and radiation protection
Theme: Radiation protection
Destination: Radiation Protection
Action type: Coordination and support actions
Countries involved: Germany,Germany,United Kingdom,Russian Federation,United Kingdom,France,United Kingdom,Netherlands,Luxembourg
Call:  (FP7-Fission-2008, 2008)
Start date: 2009-04-01
End date: 2012-09-30
Duration (months): 42.0
Total project cost (EUR): 1309223.0
EU funding (EUR): 983987.0
Participants: 9
Project status: CLOSED

The sharing of data and biomaterials from publicly funded experimental radiation science adds enormous value to the original investment. Sharing will yield substantial scientific rewards through re-analysis and new investigations. The goal of STORE is to generate a platform that will allow the storage and retrieval of both data and the corresponding biological material from past, current and future radiobiological studies. The STORE project will perform four tasks: 1) Deliver a “Data Warehouse” that will also present a single portal to radiobiological information distributed over scientific centres throughout the world. 2) Provide a foundation for the creation of a “virtual” store of biological material. 3) Establish Standard Operating Procedures (SOPs) on how best to evaluate, store and use the biological material to ensure that the collection, archiving and storage of these non-renewable materials are state-of-the-art. 4) Assess potential financial models for long term support of a bioresource and Data Warehouse for radiobiology. STORE will thus provide a mechanism for ensuring the future survival of these invaluable and irreplaceable resources and provide a platform for the sharing of new data across the radiobiology community

Keywords: radiobiological archives,access to data and material,long-term storage
Imaging regulatory pathways of angiogenesis (IMAGO)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: Israel
Call:  (ERC-2008-AdG, 2008)
Start date: 2009-01-01
End date: 2013-12-31
Duration (months): 60.0
Total project cost (EUR): 2278344.0
EU funding (EUR): 2278344.0
Participants: 1
Project status: CLOSED

Homeostasis of multicellular tissues relies on accurate match of vascular supply and drain to the needs of the tissue. Multiple pathways are involved in detection, signalling and execution of the required steps involved in organization of blood and lymphatic vessels during embryonic development. Similar mechanisms are utilized for overcoming changes in tissue requirements also in adult tissues and in pathological processes. The goal of this work is to reveal the dynamic forces that shape the blood vessels during angiogenesis. In particular, we would like to explore the impact of interstitial convective flow in dynamic imprinting of growth factor signalling, thereby regulating vascular patterning. Angiogenesis is explored here as an example for a possible general role for interstitial convection of growth factors in determination of the fine spatial patterning of tissue morphogenesis in vertebrates. To achieve this goal, we will develop multi-modality tools for imaging the regulation of vascular patterning. In vivo imaging will then be utilized for mapping vascular patterning in pathological and physiological angiogenesis including tumours, wound repair, the preovulatory ovarian follicle and foetal implantation sites. Whole body optical, CT, ultrasound and MRI will be applied for non-invasive imaging of deep organs. Microscopic morphometric and molecular information will be derived from the macroscopic imaging data, using selective molecular imaging approaches and functional imaging tools with specific pharmacological models that will be developed to account for interstitial convective flow. Intravital two photon microscopy and fluorescence endoscopy will be used for high resolution evaluation of vascular patterning. The evaluation of novel mechanisms for spatial regulation of intercellular growth factor signalling, will allow us to define new potential targets for intervention, and to develop new tools for preclinical and clinical imaging of angiogenesis.

Keywords: molecular imaging,angiogenesis,lymphangiogenesis,vascular remodeling
The role of noncoding RNA in sense and antisense or orientation in epigenetic control of rRNA genes (RIBOGENES)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Genetics, Genomics, Bioinformatics and Systems Biology
Countries involved: Germany
Call:  (ERC-2008-AdG, 2008)
Start date: 2009-03-01
End date: 2014-02-28
Duration (months): 60.0
Total project cost (EUR): 831756.0
EU funding (EUR): 831756.0
Participants: 1
Project status: CLOSED

Non-coding RNAs (ncRNAs) play a significant role in the control of gene expression and epigenetic regulation. It seems that ncRNAs might be numerous and highly adapted in roles that require specific nucleic acid recognition without complex catalysis, such as in guiding RNA modifications or in directing post-transcriptional regulation of gene expression and chromatin structure. Our previous work has revealed that NoRC, a chromatin remodeling complex that triggers heterochromatin formation and transcriptional silencing of a fraction of rRNA genes, is associated with 100-250 nt RNAs that originate from the intergenic spacer (IGS) separating rDNA repeats. Furthermore, a fraction of rDNA is transcribed in antisense orientation. Both IGS RNA and antisense transcripts display a growth- and tissue-specific expression pattern. The goal of this project is to decipher the role of NoRC-associated RNA in alterations of chromatin structure and epigenetic control of rDNA. Our research will focus on the synthesis, regulation, and processing of intergenic and antisense transcripts in response to cell growth and differentiation as well as on the role of NoRC-associated RNA in epigenetic regulation of rRNA genes. The following points will be addressed: (1) Deciphering the mechanism underlying RNA-directed establishment of specific epigenetic marks and formation of silent chromatin domains, (2) Functional analysis of posttranscriptional modifications that regulate RNA binding and NoRC activity, (3) Identification of non-ribosomal target genes of NoRC, and (4) Elucidation of the link between transcriptional activity and active demethylation of the rDNA promoter. Given the fact that basic regulatory principles are conserved throughout evolution, this work will have a great impact on our understanding of RNA-directed silencing mechanisms and will reveal how epigenetic defects cause human diseases.

Keywords: rrna genes,silencing,transcription,noncoding rna,heterochromatin,dna methylation,nucleosomes,remodeling
CAPER in Invasive Breast Cancer (CAPER/BREAST CANCE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: United Kingdom
Call:  (ERC-2008-AdG, 2008)
Start date: 2010-01-01
End date: 2014-12-31
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Breast cancer is a major cause of death in the United States and the Western World. Advanced medical technologies and therapeutic strategies are necessary for the successful detection, diagnosis, and treatment of breast cancer. Here, we propose to use novel technologies (tissue microarrays (TMA) and automated quantivative bioimaging (AQUA)) to identify new therapeutic and prognostic markers for human breast cancer. More specifically, we will study the activation status of a new signaling pathway which we have implicated in breast cancer pathogenesis, using both mouse animal models and cells in culture. For this purpose, we will study the association of CAPER expression with pre-malignant lesions and progression from pre-malignancy to full-blown breast cancer. We expect that this new molecular marker will allow us to improve diagnostic accuracy for individual patients, enhancing both the prognostic predictions as well as the prediction of drug responsiveness for a given patient.

Keywords: cancer biology,tumor progression,metastatsis,biomarkers
Molecular by-pass therapy for mitochondrial dysfunction (MITO BY-PASS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: Finland,Finland
Call:  (ERC-2008-AdG, 2008)
Start date: 2009-04-01
End date: 2015-03-31
Duration (months): 72.0
Total project cost (EUR): 2436000.0
EU funding (EUR): 2436000.0
Participants: 2
Project status: CLOSED

Many eukaryotes, but not the higher metazoans such as vertebrates or arthropods, possess intrinsic by-pass systems that provide alternative routes for electron flow from NADH to oxygen. Whereas the standard mitochondrial OXPHOS system couples electron transport to proton pumping across the inner mitochondrial membrane, creating the proton gradient which is used to drive ATP synthesis and other energy-requiring processes, the by-pass enzymes are non-proton-pumping, and their activity is redox-regulated rather than subject to ATP requirements. My laboratory has engineered two of these by-pass enzymes, the single-subunit NADH dehydrogenase Ndi1p from yeast, and the alternative oxidase AOX from Ciona intestinalis, for expression in Drosophila and mammalian cells. Their expression is benign, and the enzymes appear to be almost inert, except under conditions of redox stress induced by OXPHOS toxins or mutations. The research set out in this proposal will explore the utility of these by-passes for alleviating metabolic stress in the whole organism and in specific tissues, arising from mitochondrial OXPHOS dysfunction. Specifically, I will test the ability of Ndi1p and AOX in Drosophila and in mammalian models to compensate for the toxicity of OXPHOS poisons, to complement disease-equivalent mutations impairing the assembly or function of the OXPHOS system, and to diminish the pathological excess production of reactive oxygen species seen in many neurodegenerative disorders associated with OXPHOS impairment, and under conditions of ischemia-reperfusion. The attenuation of endogenous mitochondrial ROS production by deployment of these by-pass enzymes also offers a novel route to testing the mitochondrial (oxyradical) theory of ageing.

Keywords: mitochondria,oxphos,mitochondrial disorders
Systems Biology of Human Metabolism (SYSTEM_US)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Genetics, Genomics, Bioinformatics and Systems Biology
Countries involved: Iceland
Call:  (ERC-2008-AdG, 2008)
Start date: 2009-03-01
End date: 2014-08-31
Duration (months): 66.0
Total project cost (EUR): 2399634.0
EU funding (EUR): 2399634.0
Participants: 1
Project status: CLOSED

Whole-genome sequences and their annotation have enabled the reconstruction of genome-scale metabolic networks. Such network reconstructions form the foundation for systems analysis of metabolic functions in health and disease. Over the past ten years, a series of genome-scale reconstructions have been built for microorganisms. They have been demonstrated to be useful for developing a deeper understanding of physiological processes, drive discovery through computer generated hypothesis relating to missing parts of a network, to interpret the consequences of gene knock outs, and for metabolic engineering and bioprocess purposes. With build-35 of the human genome sequence it has proved to be possible to initiate the build of a similar genome-scale reconstruction of metabolism in man. Thus an era of systems biology analysis of human metabolic functions has just been opened, in an analogous fashion as happened for microorganisms about 10 years ago. This proposal describes a program that will lead this new era. Our three overall objectives are: 1) to continue to build the metabolic reconstruction in an iterative fashion as has been done for microorganisms in the past, 2) to deploy existing computer algorithms to systematically fill in gaps in our knowledge base about human metabolism, and 3) to use the reconstruction high-throughput data analysis and to begin the effort of drug screening and discovery for metabolic interventions. The PI has been active in this field for over 25 years, and, in fact, has been a leader in developing reconstruction technology, the computer methods that are used to characterize them, and bring them to practical uses. He has been particularly active in training young scientist in this field and been involved in translational research and company startups.

Keywords: systems biology,metabolism,in silico modeling,experimental discovery,drug screening
The Evolution of Culture (EVOCULTURE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Evolutionary, population and environmental biology
Countries involved: United Kingdom
Call:  (ERC-2008-AdG, 2008)
Start date: 2009-04-01
End date: 2015-03-31
Duration (months): 72.0
Total project cost (EUR): 2128195.0
EU funding (EUR): 2128195.0
Participants: 1
Project status: CLOSED

The capacity for culture is clearly a critical factor underlying the success of our species, but how and why did it evolve? What are the selection pressures that favoured the evolution of cultural capabilities (e.g. social learning, innovation, teaching), and how has selection fashioned these to operate efficiently? The study of such abilities is central to a broad range of disciplines, and significant progress in the scientific understanding of their origin and operation will ripple out to exert considerable influence, both within and outside academia. This project utilises a broad but integrated package of highly innovative empirical and theoretical techniques, including the development of novel analytical tools that allow behavioural researchers to identify social learning and predict the diffusion of innovations, application of potentially revolutionary statistical methods for inferring causal influences on the evolution of brain and culture from correlational data, and a new empirical system providing an unparalleled opportunity to investigate the evolution and biological basis of social learning. I will also organize international competitions to identify effective social learning rules ( tournaments ), in which entrants each propose learning strategies that are pitted against each other in computer simulation, and the most effective wins a prize. Collectively, the projects offer a major step forward in our understanding of human evolution, adaptation and culture and will stimulate considerable interdisciplinary exchange.

Keywords: social learning,human evolution,cultural evolution,gene-culture co-evolution,innovation,teaching,social learning strategies
FROM TELOMERE CHROMATIN TO STEM CELL BIOLOGY (TEL STEM CELL)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: Spain
Call:  (ERC-2008-AdG, 2008)
Start date: 2009-05-01
End date: 2014-12-31
Duration (months): 68.0
Total project cost (EUR): 2000000.0
EU funding (EUR): 2000000.0
Participants: 1
Project status: CLOSED

Telomeres are ribonucleoprotein complexes at the ends of chromosomes that are essential for chromosome protection and genomic stability. Telomeres consist of tandem TTAGGG repeats bound to a 6-protein complex known as shelterin. More recently, telomeres have been also shown to contain long non-coding telomeric RNAs (TelRNAs or TERRAs), which are associated to the telomeric chromatin and have been proposed to be potential regulators of telomerase activity and telomere length. In addition, telomeric chromatin is enriched in epigenetic marks characteristic of constitutive heterochromatin, such as histone trimethylation (H3K9 and H4K20 tri-methylation) and DNA hypermethylation, which act as negative regulators of telomere length. Telomere length defects are associated to both cancer and aging processes, and have been recently shown to have a profound effect on stem cell behaviour. Here, we propose to determine the role of both genetic and epigenetic telomere regulators in cancer and aging by generating new mouse models. Finally, we will study the role of these factors in stem cell biology.

Keywords: telomeres,telomerase,chromatin,cancer,ageing,stem cells
Systems Biology to understand Plant Architecture (SYSARC)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: Netherlands,Netherlands
Call:  (ERC-2008-AdG, 2008)
Start date: 2009-01-01
End date: 2013-12-31
Duration (months): 60.0
Total project cost (EUR): 2240000.0
EU funding (EUR): 2240000.0
Participants: 2
Project status: CLOSED

Extensive feedback between gene expression state and the cellular environment yields tangled hierarchies . This lack of strictly hierarchical control mechanisms poses a challenge to developmental biologists: the outcome of interaction networks with extensive feedbacks is not intuitive and must be analyzed with analytical tools. Here, I propose a combination of experimental and theoretical approaches to study control mechanisms of plant architecture and their emergent properties. The plant hormone auxin appears to be a major player in developmental patterning and architecture. We and others have shown previously that auxin distribution patterns can self-organize and elaborate different architectures by principles of self-organization. We have discovered that the PLETHORA transcription factors, which form instructive gradients during root development, are involved in early embryo and shoot development as well, and that they constitute a principal component of plant development. Excitingly, PLETHORA genes are regulated by auxin accumulation but they feed back on the most important actors that determine auxin distribution, the PIN proteins. The dynamics of this PLETHORA-PIN loop can display emergent properties that may explain the majority of principal patterning events that determine root and shoot specification as well as branching. Here, I propose to investigate this feedback system in detail using (1) molecular genetic approaches, (2) computer modelling and (3) functional genomics approaches. The projected outcomes are a deep understanding of major control mechanisms for tissue pattern and organismal architecture and general insights into genetic information encoding using tangled hierarchies.

Keywords: stem cells transcriptional networks
Polycomb in development, genome regulation and cancer (FLYINGPOLYCOMB)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Genetics, Genomics, Bioinformatics and Systems Biology
Countries involved: France
Call:  (ERC-2008-AdG, 2008)
Start date: 2009-09-01
End date: 2015-08-31
Duration (months): 72.0
Total project cost (EUR): 2200000.0
EU funding (EUR): 2200000.0
Participants: 1
Project status: CLOSED

Polycomb group (PcG) and trithorax group (trxG) genes were discovered in Drosophila melanogaster as repressors and activators of Hox genes, a set of transcription factors that specify the antero-posterior axis of the body plan. PcG and trxG proteins form multimeric complexes that are required to maintain their expression state after the initial transcriptional regulators disappear from the embryo. Subsequent work led to a better understanding of their mechanisms of action. Moreover, PcG and trxG genes have also been identified in vertebrates, where they regulate Hox genes, they are involved in cell proliferation, stem cell identity and cancer, genomic imprinting in plants and mammals and X inactivation. PcG and trxG components form multimeric complexes. Some trxG and PcG components possess methyltransferase activities directed toward specific lysines of histone H3, whereas other trxG and PcG proteins interpret these histone marks. Recent studies have described the genomewide distribution of PcG proteins and of their related histone modification in Drosophila and other species. However, the PcG recruitment code to their target chromatin is still not understood, and the mechanism of PcG-mediated gene silencing is unclear. The formation of subnuclear silencing compartments might contribute to the stable repression of transcription. Drosophila PcG proteins have a speckled nuclear distribution and the number of these so-called PcG bodies is progressively reduced during development. We showed that multiple PREs can associate in the nucleus to enhance the strength of PcG-mediated silencing. However, we do not know how frequent is this clustering process and how important it is functionally at a genomewide level. Our project will tackle these questions by using a combination of genetics, developmental biology, cell biology, genomics and bioinformatic approaches, with the aim to gain an integrated understanding of the role of Polycomb and trithorax in biology

Keywords: polycomb,trithorax,nuclear organization,chromosome,chromatin,development,drosophila,cancer,notch