Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Time, space and speed: cdGMP signaling in cell behavior and reproduction. (CDGMP)

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: Switzerland
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-05-01
End date: 2018-04-30
Duration (months): 60.0
Total project cost (EUR): 2496000.0
EU funding (EUR): 2496000.0
Participants: 1
Project status: CLOSED

Bacterial biofilms are the primary cause of chronic infections and of resulting infection relapses. To be able to interfere with bacterial persistence it is vital to understand the molecular details of biofilm formation and to define how motile planktonic cells transit into surface-grown communities. The nucleotide second messenger cyclic di-guanosinemonophosphate (cdGMP) has emerged as a central regulatory factor governing bacterial surface adaptation and biofilm formation. Although cdGMP signaling may well represent the Achilles heel of bacterial communities, cdGMP networks in bacterial pathogens are exquisitely complex and an integrated cellular system to uncover the details of cdGMP dynamics is missing. To quantitatively describe cdGMP signaling we propose to exploit Caulobacter crescentus, an organism with a simple bimodal life-style that integrates the sessile-motile switch into its asymmetric division cycle. We aim to: 1) identify the role and regulation of all diguanylate cyclases and phosphodiesterases that contribute to the asymmetric cellular program with the goal to model the temporal and spatial distribution of cdGMP during development; 2) identify and characterize cdGMP effectors, their downstream targets and cellular pathways; 3) elucidate how cdGMP coordinates cell differentiation with cell growth and propagation; 4) unravel the role of cdGMP as an allosteric regulator in mechanosensation and in rapid adaptation of bacteria to growth on surfaces; 5) develop novel tools to quantitatively describe cdGMP network dynamics as the basis for mathematical modeling that provides the predictive power to experimentally test and refine important network parameters. We propose a multidisciplinary research program at the forefront of bacterial signal transduction that will provide the molecular and conceptual framework for a rapidly growing research field of second messenger signaling in pathogenic bacteria.

Keywords: biofilm,chronic infections,surface adhesion,mechanosensation,c-di-gmp,caulobacter crescentus,cell biology,development,temporal and spatial regulation,cellular gradients,signaling network
Axon survival: the role of protein synthesis (AXONSURVIVAL)

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: United Kingdom
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-03-01
End date: 2018-09-30
Duration (months): 67.0
Total project cost (EUR): 2426572.8
EU funding (EUR): 2426572.8
Participants: 1
Project status: CLOSED

Neurons make long-distance connections with synaptic targets via axons. These axons survive throughout the lifetime of an organism, often many years in mammals, yet how axons are maintained is not fully understood. Recently, we provided in vivo evidence that local mRNA translation in mature axons is required for their maintenance. This new finding, along with in vitro work from other groups, indicates that promoting axonal protein synthesis is a key mechanism by which trophic factors act to prevent axon degeneration. Here we propose a program of research to investigate the importance of ribosomal proteins (RPs) in axon maintenance and degeneration. The rationale for this is fourfold. First, recent genome-wide studies of axonal transcriptomes have revealed that protein synthesis (including RP mRNAs) is the highest functional category in several neuronal types. Second, some RPs have evolved extra-ribosomal functions that include signalling, such as 67LR which acts both as a cell surface receptor for laminin and as a RP. Third, mutations in different RPs in vertebrates cause unexpectedly specific defects, such as the loss of optic axons. Fourth, preliminary results show that RP mRNAs are translated in optic axons in response to trophic factors. Collectively these findings lead us to propose that locally synthesized RPs play a role in axon maintenance through either ribosomal or extra-ribosomal function. To pursue this proposal, we will perform unbiased screens and functional assays using an array of experimental approaches and animal models. By gaining an understanding of how local RP synthesis contributes to axon survival, our studies have the potential to provide novel insights into how components conventionally associated with a housekeeping role (translation) are linked to axon degeneration. Our findings could provide new directions for developing therapeutic tools for neurodegenerative disorders and may have an impact on more diverse areas of biology and disease.

Keywords: mrna,local translation
Molecular Self Screening for Cervical Cancer Prevention (MASS-CARE)

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: Netherlands
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-06-01
End date: 2017-05-31
Duration (months): 48.0
Total project cost (EUR): 1999995.6
EU funding (EUR): 1999995.6
Participants: 2
Project status: CLOSED

Cervical carcinoma is a preventable cancer caused by a persistent infection with high-risk types of human papillomavirus (hrHPV). Several western countries have implemented nation-wide screening programs based on the detection of abnormal cells in cervical smears (cytology) for cervical cancer prevention. Although these programs have markedly reduced incidence in developed countries, even the most sophisticated cytology-based screening programs miss significant numbers of high-grade cervical lesions and fail to further reduce cervical cancer incidence. Besides loss to follow-up of women with abnormal cytology, the major causes underlying failure are: - Low sensitivity of the primary cytology based screening test, which is subjective, often not or poorly quality assessed (QA) and has low sensitivity for precancerous lesions - Incomplete coverage of women invited to participate in the screening program Remarkably, in developed countries with a successful nation-wide cervical screening programme 55% of all carcinomas are diagnosed in women who do not participate. Moreover, the lack of QA cytology in medium and low resource countries is one of the main reasons why incidence and mortality stay high in these countries. In recognition of these shortcomings the MASS-CARE project envisions a novel, objective, full molecular self-screening approach that enables molecular screening and triage for referral to the gynaecologist using self-collected cervico-vaginal samples as an alternative tool for cervical cancer screening. In particular, we aim to discover molecular triage markers specific for the stratification of women with hrHPV positive self-samples. The research team headed by professor Meijer has a strong track record of cutting edge translational research, has state-of-the art molecular tools in place and is equipped with unique biobanks of clinical cohorts of thousands of hrHPV positive women that are needed to successfully execute this ambitious project.

Keywords: self-sampling,marker discovery,triage,cervical cancer,nationwide screening,prevention,human papiloma virus,methylation,microrna
Cycloidal Rotor Optimized for Propulsion (CROP)

Framework: FP7 — Cooperation
Programme: Transport (including Aeronautics)
Destination: Aeronautics and air transport
Action type: Collaborative project
Countries involved: Portugal,Italy,United Kingdom,Austria,Germany
Call:  (FP7-AAT-2012-RTD-L0, 2012)
Start date: 2013-01-01
End date: 2014-12-31
Duration (months): 24.0
Total project cost (EUR): 780846.2
EU funding (EUR): 599993.0
Participants: 6
Project status: CLOSED

The CROP project introduces an innovative propulsion system for aircrafts based on the cycloidal rotor concept, using an integrated approach that includes the electric drive train, airframe integration and an environmental friendly energy source. The CROP system is supported on a multiphysics approach: 1. The high thrust is obtained by unsteady-based cycloidal rotor operation; 2. The development of low-weight electric power drives for the system; 3. Airframe re-design to accomplish optimum integration of the cycloidal propulsor; 4. Environmental friendly energy source based on hydrogen and photovoltaic cells. The strengths of the CROP concept are: - High thrust levels: by using unsteady airflows - Low weight: using an integrated design approach between airframe and cycloidal propulsor - Environmental friendly: because it is based on green energy power sources. The revolutionary CROP propulsion concept will introduce new air-vehicle concepts, overcoming traditional limitation on short take-off and landing, including hovering capability.

Keywords: cycloidal rotor,propulsion,airframe integration,green aircraft,photovoltaic,fuel cells
Biomechanical diagnostic, pre-planning and outcome tools to improve musculoskeletal surgery (BIOMECHTOOLS)

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: Netherlands,Netherlands
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-05-01
End date: 2018-04-30
Duration (months): 60.0
Total project cost (EUR): 2456400.0
EU funding (EUR): 2456400.0
Participants: 2
Project status: CLOSED

The aetiology of many musculoskeletal (MS) diseases is related to biomechanical factors. However, the tools to assess the biomechanical condition of patients used by clinicians and researchers are often crude and subjective leading to non-optimal patient analyses and care. In this project innovations related to imaging, sensor technology and biomechanical modelling are utilized to generate versatile, accurate and objective methods to quantify the (pathological) MS condition of the lower extremity of patients in a unique manner. The project will produce advanced diagnostic, pre-planning and outcome tools which allow clinicians and researchers for detailed biomechanical analysis about abnormal tissue deformations, pathological loading of the joints, abnormal stresses in the hard and soft tissues, and aberrant joint kinematics. The key objectives of this proposal are: 1) Develop and validate image-based 3-D volumetric elastographic diagnostic methods that can quantify normal and pathological conditions under dynamic loading and which can be linked to biomechanical modelling tools. 2) Create an ultrasound (US)-based system to assess internal joint kinematics which can be used as a diagnostic tool for clinicians and researchers and is a validation tool for biomechanical modelling. 3) Generate and validate an ambulant functional (force and kinematic) diagnostic system which is easy to use and which can be used to provide input data for biomechanical models. 4) Create and validate a new modelling approach that integrates muscle-models with finite element models at a highly personalized level. 5) Generate biomechanical models which have personalized mechanical properties of the hard and soft tissues. 6) Demonstrate the applicability of the personalized diagnostic and pre-planning platform by application to healthy individuals and patient subjects. Support from the ERC will open new research fields related to biomechanical patient assessment and modeling of MS pathologies.

Keywords: musculoskeletal disease,imaging,sensor technology,biomechanical modelling,elastographic diagnostics,joint kinematics,muscle-models,finite element,personalized diagnosis,pre-planning platform
Structure, function and evolution of bacterial root microbiota (ROOTMICROBIOTA)

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: Germany
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-03-01
End date: 2018-02-28
Duration (months): 60.0
Total project cost (EUR): 2489879.0
EU funding (EUR): 2489879.0
Participants: 1
Project status: CLOSED

The plant root defines the interface between a multicellular eukaryote and soil, one of the richest microbial ecosystems on earth. Roots grow in intimate association with a root microbiota that is distinct from the complex microbial community present in surrounding soil. A subset of soil bacteria is able to multiply inside roots as benign endophytes and modulate plant growth and development, with implications ranging from enhanced crop productivity to phytoremediation. Endophytic colonization represents an apparent paradox of plant innate immunity because plant cells can detect an array of evolutionary conserved microbe-associated molecular patterns to initiate immune responses and terminate microbial multiplication. We have developed an experimental platform to characterize soil, rhizosphere (the zone of soil influenced by roots) and root-inhabiting bacterial communities of Arabidopsis thaliana, grown in contrasting natural soils under controlled environmental conditions. This revealed that A. thaliana roots are preferentially colonized by Proteobacteria, Bacteroidetes, Chloroflexi and Actinobacteria, and each bacterial phylum is represented by a dominating class or family. Soil type defines the composition of root-inhabiting bacterial communities and host genotype determines their ribotype profiles to a limited extent. The identification of soil type-specific members within the root-inhabiting assemblies supports our conclusion that these represent soil-derived root endophytes. I propose to apply reductionist approaches to examine microbiota evolution and functions within in a single phylogenetic framework of host species. Towards this objective, we will utilize a combination of genomics, cell biological and microbial transplantation tools.

Keywords: plant microbiota,plant innate immunity,bacteria
Thymopoiesis: From Evolutionary Origins to Future Therapies (EVOTHYME)

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: Germany
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-06-01
End date: 2018-12-31
Duration (months): 67.0
Total project cost (EUR): 2496900.0
EU funding (EUR): 2496900.0
Participants: 1
Project status: CLOSED

The role of the thymus in cell-mediated immunity was discovered about 50 years ago and it has since become apparent that the thymus is the site of T cell development in all extant vertebrates. Although it has been recognized that thymopoiesis can only be fully understood by the analysis of both the thymic epithelial microenvironment and the intrathymic haematopoietic compartment, significant gaps in our knowledge of thymopoiesis remain. The proposal addresses major biological questions of thymopoiesis in a novel way. It is based on an evolutionarily informed approach that makes iterative use of distinct animal models (fish and mouse), and additionally considers information obtained from the analysis of human patients with thymopoietic deficiencies. The proposal aims to develop an animal model conducive to transplantation of xenogeneic haematopoietic progenitor cells. This system will be used for subsequent analysis of haematopoietic and immunological properties of genetically intractable fish species. The proposal also aims to determine the structure of genetic networks underlying the development and function of thymic epithelial cells and intrathymic T cell differentiation. This information will be used to explore the possibility of alleviating the phenotypic consequences of disease genes by interfering with the function of genes situated elsewhere in the respective genetic networks rather than by restoring faulty gene function. Evolutionarily constrained inventories of such genetic networks will be additionally used for the design of synthetic thymopoietic environments in non-cognate tissues, either using combinations of thymopoietic factors or by exploiting the thymopoietic capacity of Foxn1, a master regulator of thymic epithelial cell differentiation. Overall, the proposal aims at the development of evolutionarily informed genetic and cell-based strategies to reverse failing thymus function.

Keywords: thymus,immunodeficiency,evolution,zebrafish
Generation of stem cell derived photoreceptors for the treatment and modelling of retinal degeneration (STEMRD)

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-2012-ADG_20120314, 2012)
Start date: 2013-11-01
End date: 2018-10-31
Duration (months): 60.0
Total project cost (EUR): 2438482.0
EU funding (EUR): 2438482.0
Participants: 1
Project status: CLOSED

Retinal degenerations leading to loss of photoreceptors are a major cause of untreatable blindness in the EU. Age-related macular degeneration (AMD) affects 1 in 10 people over 60 yrs. Currently no treatments restore lost photoreceptor cells and visual function and thus there is a need for new therapeutic approaches. We have shown previously that transplantation of rod precursor cells at a specific stage of development results in integration and differentiation into rod photoreceptors (Nature, 2006) and that this can improve vision in mouse models of visual dysfunction (Nature, 2012). These studies provide proof-of-concept for effective transplantation of neurons and the basis for ES cell-derived photoreceptor transplantation. Importantly, these results are only achieved using photoreceptor precursor cells that are specified to differentiate into photoreceptors, but are not mature photoreceptors at the time of transplantation. The objective of this proposal is to determine if ES/iPS cell-derived photoreceptors can be utilised as a therapeutic source of cells to repair the degenerate retina and to model photoreceptor disorders. We will build on our achievements in the field of donor photoreceptor cell transplantation and determine if mouse and human ES cells have the potential to provide an efficient source of rod photoreceptor precursors for restoring vision. A key requirement for the development of retinal stem cell therapy is effective generation and transplantation of ES-derived cone photoreceptor precursors. We will modulate differentiation pathways in order to enrich for cone precursors and investigate their ability to restore visual responses in animal models of cone dysfunction. Finally, we will develop protocols for generating mature photoreceptor cells with outer segments from human iPS cells in order to model photoreceptor disease.

Keywords: retinal degeneration,embryonic stem cells,ips cells,photoreceptor.
Mechanistic analysis of DNA damage bypass in the context of chromatin and genome replication (DAMAGE BYPASS)

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: Germany
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-03-01
End date: 2018-02-28
Duration (months): 60.0
Total project cost (EUR): 2476388.4
EU funding (EUR): 2476388.4
Participants: 1
Project status: CLOSED

During its duplication, DNA, the carrier of our genetic information, is particularly vulnerable to decay, and the capacity of cells to deal with replication stress has been recognised as a major factor protecting us from genome instability and cancer. A major pathway that allows cells to overcome or bypass DNA lesions during replication is activated by posttranslational modifications of the sliding clamp protein PCNA. Whereas monoubiquitylation of PCNA allows mutagenic translesion synthesis by damage-tolerant DNA polymerases, polyubiquitylation is required for an error-free pathway that involves template switching to the undamaged sister chromatid, involving a recombination-like mechanism. Hence, damage bypass contributes to genome maintenance, but can itself be a source of genomic instability. It is therefore not surprising that PRR is a highly regulated process whose activity is limited to the appropriate situations by stringent control mechanisms. The proposed project aims at understanding DNA damage bypass in its cellular context. Using a combination of new and established technology, we will address the role of chromatin dynamics in the reaction, its spatial and temporal control in relation to genome replication, and its coordination with other PCNA-dependent processes in the cell. To this end, we will establish technology to isolate and analyse the composition of damage bypass tracts, develop and implement novel methods to induce lesions and image damage processing in live cells, and exploit a spectrum of biochemical and biophysical techniques to investigate the role of PCNA as a molecular tool-belt in the coordination of its interaction partners. In combination, these approaches will give important insight into how the replication of damaged DNA is managed with high efficiency and accuracy within the cell.

Keywords: dna damage,mutagenesis,chromatin,pcna,ubiquitin,translesion synthesis,dna repair,dna replication
Coordination Action for the early implementation of the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Coordination and support actions
Countries involved: Sweden,Netherlands,Germany,Romania,Spain,France,United Kingdom,Israel
Call:  (FP7-JPROG-2012-RTD, 2012)
Start date: 2012-09-01
End date: 2016-02-29
Duration (months): 42.0
Total project cost (EUR): 2497205.0
EU funding (EUR): 1996726.0
Participants: 11
Project status: CLOSED

This Coordination and Support Action proposal aims at aiding the implementation of the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). JPIAMR currently has 18 participating countries and organisations from 8 of these are active partners of the CSA consortium. This proposal describes in detail the different work packages (WPs) that have been suggested in order to secure the rapid implementation of JPIAMR as a mature European partnership. In summary, WP1 delivers the coordination and management needed for efficient operation, WP2 delivers a communication strategy to ensure that everyone in the field is made aware of JPIAMR. Efficient communication strategies will enable cooperation, which will be further explored in WP5 on stakeholders’ involvement. WP3 delivers an SRA, which WP4 will implement. Both of these steps will be done in close collaboration with WP5 to ensure that input from relevant stakeholders is taken into account. Finally, WP6 will enable a framework for the evaluation of the initiative as well as set the rules for IPR. By this, the aim of the JPIAMR – to integrate relevant scientific fields across national borders and to create a common European research agenda with a shared common vision – will be addressed.

Keywords: antimicrobial resistance,international cooperation