Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Cell cycle regulation of ES cell identity and reprogramming potential (REPLENICHE)

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: United Kingdom
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-05-01
End date: 2017-04-30
Duration (months): 60.0
Total project cost (EUR): 2038170.0
EU funding (EUR): 2038170.0
Participants: 1
Project status: CLOSED

Pluripotent embryonic stem (ES) and germ (EG) cells differ from other stem cells in several respects. They display a characteristically ‘compressed’ cell cycle in which G1 is shortened, contain a high proportion of cells in DNA synthesis (S)-phase and lack several cell cycle checkpoints. This unusual cell cycle signature is important for maintaining their identity since cell cycle arrest, or lengthening, results in irreversible differentiation, and somatic cells assume this unusual signature when successfully reprogrammed. We have shown that ES and EG cells rapidly convert somatic cells towards pluripotency in transient heterokaryons, and this can be enhanced by genetic modification or using ES cells enriched at G2-phase. On the other hand, mouse epiblast stem (EpiS) and ES cells that lack specific repressor activities (such as Polycomb) although pluripotent, do notdominantly convert somatic cells and show increased doubling times. To determine the importance of cell cycle control for pluripotent self-renewal, we have optimised elutriation to allow the isolation of ES, EG and EpiS cells at progressive stages of the cell cycle. Pilot studies show changes in the levels of modified histones as ES cells transit the cell cycle, and increased levels of specific reprogramming factors during G2-phase. We will extend these analyses genome wide (using ChIP and RNA Seq, and high throughput proteomics) and use fluorescent microscopy to document changes in chromatin dynamics during ES cell cycle, and during somatic cell reprogramming. This will be achieved using novel micro-fluidic approaches to generate heterokaryons between ES, EG, EpiS and lymphocytes. The importance of cell cycle stage and its relevance during early events in successful reprogramming will be tested in heterokaryon and hybrid assays using conditional mutant cells, RNAi-based approaches and cell cycle inhibitors to block critical components.

Keywords: pluripotency,cellular memory,experimental reprogramming
Global Mapping of Synthetic Genetic Interactions in Drosophila (SYNGENE)

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-2011-ADG_20110310, 2011)
Start date: 2012-08-01
End date: 2018-07-31
Duration (months): 72.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 1
Project status: CLOSED

The genetics underlying phenotype-genotype relationships during development and disease is often complex with many genes contributing to a particular phenotypic outcome. While forward genetic screens have uncovered many mutations that are limiting at a particular stage or tissue, the majority of genes in most genomes remain genetically untouched. Recent studies in model organisms, in particular in yeast, have provided evidence for the existence of pervasive genetic interactions with large effects on many phenotypes. Such genetic factors have been rather difficult to identify in classical loss-of-function screens due to buffering and other compensatory mechanisms, therefore requiring novel methodological approaches. The systematic analysis of synthetic genetic interactions also revealed how biological systems achieve a high level of complexity with a limited repertoire of components. Large-scale studies yeast have taken advantage of deletion strains to construct matrices of quantitative interaction profiles and infer gene function. However, comparable approaches in higher organisms have been difficult to implement in a robust manner. We here propose to create the first systematic synthetic genetic interaction map of a metazoan cell. Based on methods that we recently pioneered, we will quantitatively measure genetic interactions between genes on a genome scale using Drosophila cells as a model. We will utilize the map to globally dissect the interaction between processes with a focus on signaling networks. Furthermore, we will follow-up on selected interactions by in-depth characterization. Synthetic genetic interactions will be further analyzed in vivo in tissues to complement the cell-based approaches. The project will advance new experimental and computational approaches applicable also to human cells and provide fundamental insights into the cellular circuitries that govern many processes in a metazoan cell.

Keywords: synthetic genetic interactions,drosophila,quantitative phenotyping,rnai
DNA methylation, hydroxymethylation and cancer (DNAMET)

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: Denmark
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-07-01
End date: 2017-06-30
Duration (months): 60.0
Total project cost (EUR): 2298000.0
EU funding (EUR): 2298000.0
Participants: 1
Project status: CLOSED

DNA methylation patterns are frequently perturbed in human diseases such as imprinting disorders and cancer. In cancer increased aberrant DNA methylation is believed to work as a silencing mechanism for tumor suppressor genes such as INK4A, RB1 and MLH1. The high frequency of abnormal DNA methylation found in cancer might be due to the inactivation of a proofreading and/or fidelity system regulating the correct patterns of DNA methylation. Currently we have very limited knowledge about such mechanisms. In this research proposal, we will focus on elucidating the biological function of a novel protein family, which catalyzes the conversion of 5-methyl-cytosine (5-mC) to 5-hydroxymethyl cytosine (5-hmC). By catalyzing this reaction the TET proteins most likely work as DNA demethylases, and they might therefore have a role in regulating DNA methylation fidelity. Interestingly, accumulated data has in the last 2 years shown that TET2 is one of the most frequently mutated genes in various hematological cancers. We propose to investigate the molecular mechanisms by which TET2 regulates normal hematopoiesis, how its inactivation leads to hematopoietic malignancies and how the protein contributes to the regulation of DNA methylation patterns and transcription. Furthermore, we propose several experimental approaches for identifying proteins required for the recruitment of TET proteins to target genes and to analyze their role in the regulation of DNA methylation patterns and in cancer. Finally, we will investigate the potential functional role of 5-hmC and explore the potential mechanisms by which this modification could be erased. We expect to provide new insights into the biology of DNA methylation, hydroxymethylation and contribute to unravel the roles of TET proteins in normal physiology and cancer.

Keywords: cancer,dna methylation,hydroxymethylation,transcription
Molecular exploitation of an extremophile mammal (EXTREMOPHILE MAMMAL)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: Germany
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-04-01
End date: 2018-03-31
Duration (months): 72.0
Total project cost (EUR): 2498960.0
EU funding (EUR): 2498960.0
Participants: 1
Project status: CLOSED

The African naked mole-rat (Heterocephalus glaber) is an unusual rodent species that has evolved physiological strategies to adapt to an extreme ecological niche. It is the only poikilothermic mammal (cold-blooded), has an extraordinarily long life span for its small size (in excess of 30 years) and lives in large colonies organized like those of termites (eusocial). We have shown that naked mole-rats lack physiological attributes thought essential and protective for most other animal species. For example, severe tissue acidosis is life threatening as well as painful and yet naked mole-rats completely lack behavioral sensitivity to acid and sensory neurons are not activated by protons in this species. Here we will identify functionally important naked mole-rat gene variants that may account for aspects of the extreme physiology in this species. We have already identified candidate naked mole-rat-genes whose altered function, compared to other mammals, may account for acid insensitivity, lack of pain sensitization and poikilothermy in this species. These gene variants will be functionally characterized by replacing the mouse gene with a naked-mole rat variant using molecular genetic techniques. In addition we will use next generation sequencing to identify further naked mole-rat gene variants. These studies will allow us to learn how evolution selected for functionally significant gene variants that can radically alter normal physiology in the context of a rodent genome.

Keywords: ion channels,thermogenesis,next generation sequencing,neurotrophins,tyrosine kinase receptors,nociception,metabolism,aging,acid nociception,hyperalgesia
Investigating the biology of plant infection by the rice blast fungus Magnaporthe oryzae (GENBLAST)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Applied life sciences and biotechnology
Countries involved: United Kingdom
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-03-01
End date: 2017-12-31
Duration (months): 70.0
Total project cost (EUR): 2498733.0
EU funding (EUR): 2498733.0
Participants: 1
Project status: CLOSED

Plant diseases represent one of the most important risks to ensuring global food security and new control strategies for the world’s most serious crop diseases are urgently needed. This project will lead to an unparalleled advance in understanding of the world’s most serious crop disease - rice blast. Each year rice blast disease claims 11-30% of the potential rice harvest, which is enough rice to feed 60 million people. The fungus that causes rice blast disease, Magnaporthe oryzae, is a highly adapted cereal pathogen, which forms specialized infection structures called appressoria that can breach the intact leaf surface and allow the fungus entry to living plant tissue. This project will result in the most comprehensive understanding of the biology of plant infection by a pathogenic fungus. The cross-disciplinary research programme will integrate next generation DNA sequencing, digital transcriptional profiling, and high throughput gene functional analysis, with cell biology and live cell imaging. In this way, the transcriptional networks and gene regulators of fungal virulence will be identified and characterized at a systems level. The project will investigate the nature of the host-pathogen interface using live cell imaging of stable transgenic rice lines expressing fluorescent fusion proteins that define specific sub-cellular domains and will allow the precise mechanism of cellular invasion by the fungus to be determined. The project will also use protein-protein interaction studies to identify the major effectors used by M. oryzae to suppress plant immunity and facilitate proliferation of the fungus within living plant tissue. In parallel, comparative genome analysis will define conserved the full repertoire of effector functions and the transcriptional networks necessary for plant disease. Comprehensive functional analysis of M. oryzae effectors will then be carried out by targeted gene deletion, spatial localization and target identification.

Keywords: fungal biology genomics developmental biology plant disease appressorium plant microbe interactions virulence effector proteins plant immunity fungal pathogenicity crop disease
The input of mechanical forces to morphogenesis and wound healing: a systematic dissection (MORPHORCE)

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: France,France
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-05-01
End date: 2018-04-30
Duration (months): 72.0
Total project cost (EUR): 2495504.0
EU funding (EUR): 2495504.0
Participants: 2
Project status: CLOSED

The importance of mechanical forces in biology is well accepted, yet an integrated view of their mode of action in vivo is lacking. We intend to characterize in-depth the physical forces and cellular processes that coordinate the morphogenesis of different cell types contributing to an organ, taking the C. elegans embryo as a paradigm. We will achieve this by pursuing three axes: 1. Building on our discovery of a hemidesmosome-based mechanotransduction pathway that operates between contracting muscles and epidermal cells, we will combine genetic analysis with single-molecule biophysical methods to address three issues. i) What is the primary mechanosensor responding to tension within hemidesmosomes and how does it work? ii) How are all epidermal targets of muscle tension activated? iii) What is the biophysical mechanism stabilizing epidermal cells between muscle contractions? 2. We will test several features of a finite element model predicting a key role of microtubule-based epidermal stiffness and hydrostatic pressure in elongation. We will combine quantitative mechanical measures with force biosensors and laser ablation to define how these resistive forces contribute to embryo elongation along the anterior-posterior axis. 3. To extend our conclusions to the medical field, we will knockdown homologues of proteins identified in C. elegans, as well as proteins of the same families, in keratinocytes with partially damaged hemidesmosomes. Cells will be submitted to wound assays or grown on a stretchable substrate. Positive hits will be further characterized and tested in mouse models with partially defective hemidesmosomes. We foresee that this project will identify conserved proteins and processes relaying mechanical forces, and thus shed light on the mechanical basis of morphogenesis. We also expect our work to have strong impact in medicine, since the outcome of many pathologies, including wound healing and cancer, is thought to be strongly influenced by forces.

Keywords: genetic analysis,c. elegans,mechanical force,mechanotransduction,single molecule force spectroscopy,hydrostatic pressure,microtubule,stiffness,biosensor,wound healing,keratinocyte
Genome-enabled dissection of marine diatom ecophysiology (DIATOMITE)

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-2011-ADG_20110310, 2011)
Start date: 2012-06-01
End date: 2017-05-31
Duration (months): 60.0
Total project cost (EUR): 2423320.0
EU funding (EUR): 2423320.0
Participants: 1
Project status: CLOSED

Diatoms are the most successful group of eukaryotic phytoplankton in the modern ocean. Recently completed whole genome sequences have revealed a wealth of information about the evolutionary origins and metabolic adaptations that may have led to their ecological success. A major finding is that they have acquired genes both from their endosymbiotic ancestors and by horizontal gene transfer from marine bacteria. This unique melting pot of genes encodes novel and largely unexplored capacities for metabolic management. The project will address the current gap in knowledge about the physiological functions of diatom gene products and about the evolutionary mechanisms that have led to diatom success in contemporary oceans. We will exploit genome-enabled approaches to pioneer new research topics addressing: 1. How has diatom evolution enabled interactions between chloroplasts and mitochondria that have provided diatoms with physiological and metabolic innovations? 2. What are the relative contributions of DNA sequence variation and epigenetic processes in diatom adaptive dynamics? By combining these questions, we will uniquely be able to identify sentinel genes that have driven major physiological and metabolic innovations in diatoms, and will explore the mechanisms that have selected and molded them during diatom evolution. We will focus our studies largely on diatom responses to nutrients, in particular nitrate and iron, and will exploit the advantages of Phaeodactylum tricornutum as a model diatom species for reverse genetics. The proposed studies will revisit textbook understanding of photosynthesis and nitrogen metabolism, and will refine hypotheses about why diatoms dominate in contemporary ocean settings. By placing our studies in evolutionary and ecological contexts, in particular by examining the contribution of epigenetic processes in diatoms, our work will furthermore provide insights into how the environment selects for fitness in phytoplankton.

Keywords: evolutionary ecophysiology,microbial oceanography
Early infectious, inflammatory and immune mechanisms in schizophrenia (EIMS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: ERC Advanced Grant Interdisciplinary Panel
Countries involved: Denmark
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-05-01
End date: 2017-04-30
Duration (months): 60.0
Total project cost (EUR): 2471736.0
EU funding (EUR): 2471736.0
Participants: 1
Project status: CLOSED

The ambitious goal of this proposal is to identify causal mechanisms in schizophrenia, a devastating disease affecting about 1 percent of the population worldwide, and for which there is no current prevention or cure. If my team and I are successful, we will discover etiological factors that can be targets for preventive interventions on the general population level and in high-risk groups, as well as inform the development of novel treatments. I will use a truly unique population-based set of registers and biobanks, based upon a total national Danish birth cohort of more that 1.6 million individuals, and apply a novel combination of epidemiological design and methods and molecular biological techniques to the study of early risk factors for schizophrenia: I propose to combine cohort, nested case-control and case-sibling designs in studies of this total national birth cohort with detailed biological assessment of genetic and environmental risk factors operating during fetal life and around birth, in combination with detailed longitudinal information about the life course of cases, controls and their relatives. Together with my team, I will for the first time in a human population empirically test a range of novel and specific hypotheses, tied together by a common theoretical framework of inflammatory and immune mechanisms interacting with individual genetic vulnerability during fetal life. Specifically the focus will be on infectious agents, markers of inflammation, effects of maternal auto-antibodies, and interactions with maternal vitamin D as well as genes involved in apoptosis and other relevant pathways. All findings will be tested in independent replication samples from the same population and further validated by comparison to healthy sibling controls. Because my studies are performed in a total population birth cohort, we will be able to make risk prediction suitable for the identification of targets for preventive strategies.

Keywords: schizophrenia,neurodevelopment
Cognitive-Networks-Enabled Transnational Proactive Healthcare (CoNHealth) (CONHEALTH)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Research Staff Exchange Scheme
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom,Italy,Finland
Call:  (FP7-PEOPLE-2011-IRSES, 2011)
Start date: 2012-04-01
End date: 2016-03-31
Duration (months): 48.0
Total project cost (EUR): 453600.0
EU funding (EUR): 420000.0
Participants: 3
Project status: CLOSED

CoNHealth will bring together leading researchers with wide-ranging research experience in the context of a collaborative scheme of research exchanges and networking to advance current knowledge in the area of intelligent wireless networks for medical ICT applications. The project is endorsed by 8 institutions including 3 partners from EU countries (UK, Italy, and Finland), 2 partners from industrialized third countries (US and Japan), and 3 partners from an International Cooperation Partner (ICP) country (China). The members of the consortium will provide complementary knowledge and strength in the areas of cognitive radio, cognitive radar, cognitive sensor, privacy and security in healthcare, medical sensors and instrumentation, disease management and diagnosis, biomedical signal processing, and medical ICT. These capabilities have been drawn out in accordance with the joint research vision of providing transnational proactive healthcare (TPH), commonly shared by the partners at the moment of writing the proposal. By developing an integrated cognitive network platform, it is our conviction that reliable, comprehensive, and efficient data acquisition from various medical sensors and devices, and their harmonious transmission and delivery to remote caregivers can be achieved. The project will consist of targeted research activities undertaken by key individual researchers, supported by PhD students, early-career academics, and professors. The exchanges will enable the reciprocal transfer of knowledge between the members of the consortium and will be deployed by a set of designated activities open also to external stakeholders. As the consortium comprises members from both industrialized and ICP countries across 3 different continents, the research outputs would benefit the wider population in a worldwide perspective, which can hardly be achieved if each individual partner works alone on this topic.

Keywords: cognitive network platform,distributed diagnosis and home healthcare,cognitive radio,cognitive radar,cognitive sensor,privacy and security solutions,research staff exchange and networking