Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
A System Approach to Hox Genes Regulation in Vertebrates (SYSTEMSHOX.CH)

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: Switzerland
Call:  (ERC-2008-AdG, 2008)
Start date: 2009-02-01
End date: 2014-01-31
Duration (months): 60.0
Total project cost (EUR): 2418000.0
EU funding (EUR): 2418000.0
Participants: 1
Project status: CLOSED

The aim of this grant is to understand the relationships between genomic topology and the control of transcription, using the HoxD locus as a paradigm. We will take a system approach in the mouse, combining tools of genetics, evolutionary genomics and biochemistry to try and model various modes of large-scale gene regulations occurring during development. The results will tell us about the mechanistic bases of global gene regulation and how such regulations evolved, by integrating these mechanisms into the evolutionnary contexts of the respective structures. The approach will make use of our unique collection of mutants at this locus along with both transcript profiling and quantitation, ChIP of several proteins (modifications thereof-) indicative of chromatin states, chromosome conformation capture (4C) and transgenesis after phylogenetic footprint. To keep datasets within reasonable scales and allow for their integration into a single model structures, we will focus on a 2 Mb large DNA interval centered around the HoxD locus, which contains range of conserved non-coding DNA sequences and includes a gene-rich island, flanked by two large gene-deserts bordered again by gene-rich regions. We will conduct systematic analyses of these multiple parameters in various embryonic tissues, at different times where and when Hox genes are required. The massive datasets generated (ca 15 different points for transcript quantification, profiling, chromatin modifications, 4C, from ca 10 different tissues at 3 developmental times, from as many as 20 mutant strains) will feed mechanistic models accounting for the modalities of these regulations. Models will be compared to one another to try and reconstitute the evolution of these regulations. Such a combination of genetics, biochemistry and modeling, carried out on a locus where global gene function is already well worked out, will give us a comprehensive view of the underlying regulatory mechanisms, with a high heuristic value

Keywords: morphogenesis,transcription factors,development,evolution,chromosome conformation capture,chip on chip,tilling arrays,cngs,gene regulation,modeling
Homeostasis and rupture of the gut epithelium in the presence of commensals and pathogens (HOMEOEPITH)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Immunity and infection
Countries involved: France
Call:  (ERC-2008-AdG, 2008)
Start date: 2009-02-01
End date: 2014-03-31
Duration (months): 62.0
Total project cost (EUR): 2356350.0
EU funding (EUR): 2356350.0
Participants: 1
Project status: CLOSED

The molecular cross talks occuring at the interface between the intestinal epithelium and bacterial flora will be studied at two levels : (i) how commensals and pathogens affect innate immune signalling, thereby leading to tolerance of the resident microbiota, and inflammatory rejection of the pathogens. The theme of commensals and pathogens regulating this innate response, particularly how they respectively strengthen or weaken the network of humoral and cellular epithelial defense systems will be central here. (ii) How, in molecular and cellular terms, bacteria affect epithelial renewal. The gut of a germ-free mouse and of a conventional mouse show dramatic differences marked by global immaturity and slow epithelial renewal in absence of flora. In front of pathogens, the actual role plaid in the disease in altering the kinetics of epthelial repair is unknown. The aim of this project is to study how commensals and pathogens affect intestinal epithelial renewal, particularly the key steps of the whole developmental process such as lineages decisions, entry in cycle and proliferation, migration and final differentiation, decision to engage in cell death. In order to address these fundamental questions, we will study a commensal microorganism : Lactobacillus casei, and a pathogenic microorganism : Shigella flexneri as model organism, and will develop several novel systems such as reverse genetics of Lactobacilli, development of intestinal crypt models in vitro to study bacterial interactions, and development of a mouse model showing susceptibility to human-specific enteroinvasive pathogens. This project aims at interfacing microbiology, cell biology, and development biology around the concept of microbes manipulating intestinal epithelial homeostaesis. It also includes a strong component of therapeutic development aimed at identifying novel anti-infectious strategies and options to speed up epithelial restitution upon infectious-inflammatory damages.

Keywords: commensal bacteria pathogens intestinal crypt homeostasis innate immunity anti-infectious
LGR receptors mark adult stem cells in multiple mammalian tissues (STEMCELLMARK)

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
Call:  (ERC-2008-AdG, 2008)
Start date: 2009-03-01
End date: 2014-02-28
Duration (months): 60.0
Total project cost (EUR): 2106000.0
EU funding (EUR): 2106000.0
Participants: 1
Project status: CLOSED

Self-renewal and repair of tissues in adult mammals is fueled by rare tissue stem cells. Identification and subsequent study of such adult stem cells depends strictly on the availability of molecular markers. To date, a paucity of single definitive markers has complicated the study of the biology of these rare cells. Our interest in the role of the Wnt pathway in intestinal homeostasis and cancer has led us to exhaustively define the Wnt target gene program shared between these two processes. Within this program, the cell surface receptor-encoding Lgr5 represented a candidate stem cell marker for the intestine. The creation of Lgr5-genetic mouse models subsequently allowed us to definitively identify the Lgr5+ cells as the intestinal stem cells. These stem cells divide every day, yet persist throughout life. Using the same mouse models, we have found that Lgr5 marks stem cells in a variety of other tissues. For two family members with similarly restricted expression domains, Lgr4 and -6, comparable genetic tools have been generated. In this proposal, I aim to exploit these unique genetic tools to study primary adult stem cells in health and disease. This should allow us to outline unique and common characteristics of individual stem cell types, and possibly- define the minimum molecular determinants of stemness. Specifically, I aim: 1. To make a complete inventory of adult stem cells expressing Lgr4, Lgr5 and/or Lgr6 using the transgenic mouse models. 2. To FACS-purify stem cells from selected tissues, and detail their molecular and metabolic characteristics. 3. To genetically define the biological role of the Lgr-family receptors in adult stem cells by gene knockout. 4. To translate these findings to the equivalent human tissues using antibody-based histology and FACS technology. 5. To explore the usefulness of the Lgr proteins as markers of cancer stem cells in human solid tumors.

Keywords: stem cell biology
Ecological, molecular, and evolutionary spatial dynamics (SPATIALDYNAMICS)

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: Finland
Call:  (ERC-2008-AdG, 2008)
Start date: 2009-01-01
End date: 2013-12-31
Duration (months): 60.0
Total project cost (EUR): 2478999.0
EU funding (EUR): 2478999.0
Participants: 1
Project status: CLOSED

The study of wild populations will benefit of increasing integration of ecological, molecular, genetic, and evolutionary approaches. The Glanville fritillary butterfly has a classic metapopulation in a network of 4,000 habitat patches in the Åland Islands, Finland, within an area of 50 by 70 km, across which population surveys have been conducted since 1993. Taking advantage of the opportunity to sample a few larvae from full-sib groups of gregarious larvae in hundreds of local populations, this project involves large-scale phenotyping and genotyping of individuals across the large metapopulation. The aim is to advance our general understanding of the genetic basis of variation in individual performance and life-time reproductive success (fitness), and the role of ongoing natural selection in population dynamics of species living in fragmented landscapes. For genotyping, we select ~1,000 SNPs from annotated genes in the recently sequenced transcriptome of this species. The same SNPs will be used to construct a pedigree for the entire metapopulation for 4 years. Two broad questions will be addressed: (1) Genetic basis of variation in dispersal, related life-history traits, and life-time reproductive success. This will be studied with association analyses, correlating individual phenotypes and genotypes to identify molecular variation with consequences for individual performance and fitness; and with pedigree analyses of natural populations, relating life-time reproductive success of individual larval groups to their phenotypic and genotypic composition. (2) Spatio-temporal population dynamics, the role of ongoing natural selection and consequences for regional adaptation. The purpose is to investigate the causes and consequences of spatio-temporal variation in population dynamics, including the role of ongoing natural selection. Mathematical modelling will be used to investigate the coupling of ecological and evolutionary dynamics in the spatial context.

Keywords: population biology,evolutionary biology,integrated biology
Ultra Fast Magnetic Resonance Imaging using One-Voxel-One-Coil Acquisition (OVOC)

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: Germany
Call:  (ERC-2008-AdG, 2008)
Start date: 2009-09-01
End date: 2015-02-28
Duration (months): 66.0
Total project cost (EUR): 2495600.0
EU funding (EUR): 2495600.0
Participants: 2
Project status: CLOSED

The proposal is aimed at the development of ultrafast Magnetic Resonance Imaging (MRI) for applications in neuroscience, neurology and oncology. The methodology used is based on the principle of one-voxel-one-coil acquisition in which the sensitive volumes of arrays containing a large number of small receiver coils is used as primary source of spatial localization. This allows to achieve acquisition speed >> 10 fps and opens up new windows of application for MRI. Within this proposal research will be aimed at two areas of application: For investigation of fast physiological events in the brain, applications based on the observation of fast spatiotemporal events by MR-encephalography (MREG) will be developed. MREG will be used for detailed quantitative measurement of differential cortical response during activation of cortical networks by complex stimuli. Primary areas of interest will be the investigation of spatiotemporal response in visual perception, visual and auditory cued tasks and during language processing. In addition to quantitative mapping of response, map functional connectivity with and without correlation with ECG will be investigated. For neurological applications we will use the very high sensitivity of MREG to detect arterial pulsatility in order to generate quantitative, three-dimensional maps of hemodynamic function. Clinical applications for examination of patients with stroke, ischemia, vascular disease and vascular pathologies will be developed. The principles of OVOC-measurements will also be applied in oncology for measurements of fast intrinsic and stimulated physiological events like dynamic measurements of blood flow, tissue permeability and oxygenation in tumors and metastasis. Spectroscopic OVOC-measurements will be developed to observe metabolic turnover. All experiments will be performed both in humans and animal models. Highly localized experiments will be performed using microcoil arrays currently under development.

Keywords: magnetic resonance imaging mr encephalography
microRNAs in vascular homeostasis (ANGIOMIRS)

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: Germany
Call:  (ERC-2008-AdG, 2008)
Start date: 2009-03-01
End date: 2014-02-28
Duration (months): 60.0
Total project cost (EUR): 2375394.0
EU funding (EUR): 2375394.0
Participants: 1
Project status: CLOSED

Despite improved therapy, cardiovascular diseases remain the most prevalent diseases in the European Union and the incidence is rising due to increased obesity and ageing. The fine-tuned regulation of vascular functions is essential not only for preventing atherosclerotic diseases, but also after tissue injury, where the coordinated growth and maturation of new blood vessels provides oxygen and nutrient supply. On the other hand, excessive vessel growth or the generation of immature, leaky vessels contributes to pathological angiogenesis. Thus, the regulation of the complex processes governing vessel growth and maturation has broad impacts for several diseases ranging from tumor angiogenesis, diabetic retinopathy, to ischemic cardiovascular diseases. MicroRNAs (miRs) are small noncoding RNAs, which play a crucial role in embryonic development and tissue homeostasis. However, only limited information is available regarding the role of miRs in the vasculature. MiRs regulate gene expression by binding to the target mRNA leading either to degradation or to translational repression. Because miRs control patterns of target genes, miRs represent an attractive and promising therapeutic target to interfere with complex processes such as neovascularization and repair of ischemic tissues. Therefore, the present application aims to identify miRs in the vasculature, which regulate vessel growth and vessel remodelling and may, thus, serve as therapeutic targets in ischemic diseases. Since ageing critically impairs endothelial function, neovascularization and vascular repair, we will specifically identify miRs, which are dysregulated during ageing in endothelial cells and pro-angiogenic progenitor cells, in order to develop novel strategies to rescue age-induced impairment of neovascularization. Beyond the specific scope of the present application, the principle findings may have impact for other diseases, where deregulated vessel growth causes or accelerates disease states.

Keywords: vascular biology,angiogenesis,ischemia,endothelial cells,signaling
A Novel Nano-container drug carrier for targeted treatment of prostate cancer (NANOTHERAPY)

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: Greece
Call:  (ERC-2008-AdG, 2008)
Start date: 2009-02-01
End date: 2014-01-31
Duration (months): 60.0
Total project cost (EUR): 2000000.0
EU funding (EUR): 2000000.0
Participants: 1
Project status: CLOSED

The essence of the proposal is the fabrication of multiple nano containers which exhibit double and triple stimuli response and site recognition. Specifically, the containers will be grafted by Leuprolide (LP) for prostate cancer recognition. Multiple containers will be filled by two drugs (e.g. LP and DOX) in different compartments not interacting with each other chemically (cocktail of drugs, e.g. Container1 Leuprolide (LP) and Container2 Doxorubicin (DOX)). The release can be excited by internal or external stimuli response. The internal stimuli response of our nanocontainers will require simultaneous recognition of pH, redox and/or T of the tumour. The external induction will be caused by RF excitation (hyperthermia). The nanocontainers will identify the tumour first by the agonist (LP). After trapping the container at the tumour, they will be activated by the double and triple internal excitation. This way, we achieve extremely local chemotherapy of the diseased site and the healthy organs will be untouched. Our smart nanocontainers will be tuned for prostate cancer, but our system will be evaluated for other cases such as breast cancer and thrombosis. The containers will be modified (phase transition, volume change, degradation, etc.) and deliver the drug only and if only the two sensors give positive response. The containers can be excited by external induction (Radio Frequency (hyperthermia) RF or laser light). This revolutionary strategy is necessary because the externally induced delivery methods have the disadvantage that the radiofrequency fields, the magnetic fields and the laser lights are not local but they extend over large space, larger than the size of the tumour. One cannot focus from outside the laser beam directly to the tumour only may be due to lack of imaging facilities. Our technology will prevent the release of drugs in sites where the local values correspond to the healthy tissue.

Keywords: nanocontainers drug delivery
Population phylogenomics: linking molecular evolution to species biology (POPPHYL)

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: France
Call:  (ERC-2008-AdG, 2008)
Start date: 2009-07-01
End date: 2013-12-31
Duration (months): 54.0
Total project cost (EUR): 2000000.0
EU funding (EUR): 2000000.0
Participants: 1
Project status: CLOSED

The aim of the PopPhyl project is to characterize the population genetic environment of many representative plant and animal species, in order to elucidate which biological and ecological factors determine molecular evolutionary processes - we want to know why genomes evolve the way they evolve. We will establish predictions about the influence of ecological (population size, varying environment) and genetical (mating systems, life cycle, mutation rate) variables on comparative genomic patterns thanks to improved molecular evolutionary theory relying on Fisher&apos;s geometric model. Predictions will be checked empirically by collecting extensive data sets of within-species and between-species genomic diversity in a large number of well-chosen taxa, with monitored life history traits. Massive gene sequences will be obtained from the extraction and analysis of abundant mRNA&apos;s, ensuring comparability between even distant taxa. These data will allow us to assess, and compare across species, the population genetic parameters relevant to molecular evolution: effective population size, mutation rate, strength of positive and negative selection. The main focus of the project is on the influence of population size, mating systems and life-span on molecular evolutionary rates. Are abundant species genetically more diverse? Do they adapt more efficiently? Is self-fertilization the evolutionary dead-end it is said to be? Why are fast-evolving proteomes fast: higher mutation rate, or prominent adaptive evolution ? PopPhyl is an ambitious, long-term multi-disciplinary project lying at the boundary of phylogenetics and population genetics, and requiring intensive theoretical and bioinformatic developments. We want to explore a new dimension of evolutionary biology by making population genetics comparative, and by injecting species ecology into genomic analyses.

Keywords: population genetics,molecular evolution,transcriptome
Dissecting the transcriptional mechanisms controlling growth during normal development and cancer (GROWTHCONTROL)

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: Sweden
Call:  (ERC-2008-AdG, 2008)
Start date: 2009-03-01
End date: 2014-02-28
Duration (months): 60.0
Total project cost (EUR): 2200000.0
EU funding (EUR): 2200000.0
Participants: 1
Project status: CLOSED

The main scientific questions addressed in this proposal relate to the understanding of molecular mechanisms of growth control and cancer through the combined use of high-throughput technologies and computational biology. We aim to create a systems-level understanding of the cell cycle, and its regulation by physiological growth factors and oncogenes through the use high-throughput biology to identify all or the majority of genes that are essential for cell cycle progression, and by combining this dataset with computationally predicted and experimentally validated target genes of growth factors and oncogenic pathways. In my opinion, such systems biology approach is critical for understanding of growth control, as organ-specific growth control has proven particularly refractory to genetic dissection. Much of what we know about physiological mechanisms controlling cellular growth in mammals has been revealed by human cancer genetics. These studies have revealed that a large number of genes can contribute to aberrant cell growth; there are more than 300 genes that have been linked to cancer, and mutations found in cancer are often cell type specific ( oncogene preference , i.e. PTCH mutations in medulloblastoma, APC in colon cancer, TMPRSS2-ERG in prostate cancer), suggesting that different pathways in different cell lineages are coupled to the cell cycle machinery. We have preliminary evidence that hedgehog (Hh) and Wnt signals are directly coupled to expression of N-myc and c-Myc genes, but only in tissues and cell-types that display a proliferative response to these factors. Both classical molecular and developmental biology as well as high throughput and systems biological methods will be used for dissection of the molecular mechanism of this selectivity. If successful, these experiments would establish a principle explaining why particular mutations are extremely common in some tumor types but not found at all in others.

Keywords: growth control,cancer,transcription,functional genomics,protein interactions,systems biology,myc