Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
The interactions of the Pseudomonas aeruginosa lectins LecA and LecB with glycosphingolipids result in membrane invagination, signaling and cellular uptake of the bacterium (LEC&LIP2INVADE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: Germany
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-12-01
End date: 2016-11-30
Duration (months): 60.0
Total project cost (EUR): 1436400.0
EU funding (EUR): 1436400.0
Participants: 1
Project status: CLOSED

Pseudomonas aeruginosa has emerged as a major opportunistic pathogen during the past century. The invasion of host cells plays a fundamental role in the pathogenesis of this bacterium. As clinically important antibiotic resistance of P. aeruginosa continues to increase, the identification of host as well as microbial factors essential for P. aeruginosa uptake may lead to new drug targets. Our highly ambitious and interdisciplinary research project at the interface of biology, chemistry and physics aims at describing the molecular mechanism of the internalization of P. aeruginosa in non-phagocytic cells. Based on novel concepts that we have established for some bacterial toxins and animal viruses, we hypothesize that specific interactions of the P. aeruginosa lectins LecA and LecB with distinct glycosphingolipids exposed at the host cell surface lead to formation of plasma membrane invaginations, activation and recruitment of signaling molecules, cytoskeleton remodeling and cellular uptake of the bacterium. In order to acquire highly complementary results and to ensure the maximal outcome, we will perform our studies on diverse animal cells and various membrane model systems in combination with super resolution imaging techniques, biochemical and screening approaches. For the in vitro reconstitution of bacterial invasion, we will develop a unique platform for membrane nanoscopy based on planar pore-suspending membrane systems of different complexity (e.g. pore-suspending plasma membrane sheets and synthetic lipid bilayers). We expect to be able to identify key factors of bacterial uptake and small molecule inhibitors towards them in order to develop new therapies against the pathogenesis of P. aeruginosa infections.

Keywords: glycobiology,pseudomonas aeruginosa,invasion,lectin,invagination,giant unilamellar vesicle,atomic force microscopy,endocytosis,trafficking,signaling,cdna screening,reconstitution,inhibitor
OsteoMotion: Analyzing the mechanisms and role of osteogenic cell movement in bone development and disease (OSTEOMOTION)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: Belgium
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-11-01
End date: 2016-10-31
Duration (months): 60.0
Total project cost (EUR): 1499200.0
EU funding (EUR): 1499200.0
Participants: 1
Project status: CLOSED

Bone development and homeostasis must incontestably rely on a correct spatial positioning of osteoblasts to generate bone at appropriate sites. A failure of osteoblasts to reach the sites in need of bone formation may contribute to impaired fracture repair and osteoporosis. Conversely, uncontrolled osteogenic cell movement may play a role in diseases involving aberrant placement of bone. Mechanisms of osteoblastic migration and adhesion may even be mimicked by bone-metastasizing tumor cells. Yet, the trafficking of osteogenic cells has been a largely neglected aspect in bone biology. My recent studies abroad for the first time shed light on this process in vivo. Newly generated transgenic mouse models for osteoblast lineage tracing revealed that specifically osteoprogenitors, and not mature osteoblasts, moved to initiate novel sites of bone formation. Intriguingly, osteoprogenitors entered developing and healing bones along with their neovascularization, some being wrapped as pericytes around the blood vessels, suggesting an unprecedented vessel-guided cell movement mechanism. Implementing these concepts and models, I here propose two angles to elucidate the mechanisms mediating osteoprogenitor motility. In a first approach, we will assess the involvement, in vitro and in vivo, of known candidate molecular targets of (i) cell-matrix interactions pivotal in cell migration, (ii) cell-cell adhesion, and (iii) the association between pericytes and endothelial cells. Secondly, a high-risk high-gain reverse approach using innovative technologies aims to identify the specific genetic profiles of motile osteoprogenitors and bone-anchored mature osteoblasts. Overall this project will bring novel mechanistic insight in osteogenic cell movement in bone biology and pathology, and add to our broader understanding of cell migration and progenitor properties. The potential to evoke new therapies to widespread skeletal pathologies underscores the study’s importance and high impact.

Keywords: osteoblast,osteoprogenitor,bone,skeleton,angiogenesis,cell migration,cell adhesion,cellular interactions,transgenic mice,development,bone pathology,conditional knock-out mice,histology.
E3 - Extreme Event Ecology (E3)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Applied life sciences and biotechnology
Countries involved: Germany
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2016-12-31
Duration (months): 60.0
Total project cost (EUR): 1487000.0
EU funding (EUR): 1487000.0
Participants: 1
Project status: CLOSED

With anthropogenic warming, extreme events have already increased in magnitude and frequency and are likely to continue to do so in the near future. These extreme events play decisive roles in climate change impacts. Natural and managed systems, such as agriculture and forestry, are more strongly affected by extremes than by a change in average conditions. Classical parameters considered have included temperature, precipitation and wind speed, but here we will concentrate on multi-factorial complex situations, such as drought, and subsequent ecological events, such as pests. Novel methods from finance mathematics and statistics will be transferred for application to natural systems in order to assess risks of extremes in past, present and future conditions. Special emphasis will be given to deriving critical thresholds and prediction for when they will be crossed. Here, analyses of long-term ecoclimatological data from dendrology, phenology, seed quality, as well as both manipulated experiments and simulations are needed to provide information on the effects stemming from multiple stressors and extremes. In contrast, real data, no matter how long-term, cannot model the risk of new threatening combinations of climatological and ecological parameters. Adaptation should therefore focus not only on retrospective but also on new extremes, in other words, should look forward to the future. In particular, low probabilities and high risk scenarios have to be taken into account. Adaptation measures can range from breeding, and selection of suitable species and varieties to management options, such as sanitation and forest protection. Insurance also needs to adapt to changes in climate and ecology and accurate forecasting becomes more critical in the face of unforeseen extremes and calamities. Thus, future risk management must be based on both adaptation and insurance, with new products, such as index insurance, facilitating the handling of customer claims.

Keywords: climate change,extreme event,divergence,tipping point,manipulation experment
Molecular Anatomy and Pathophysiology of the endoplasmic reticulum-mitochondria interface (ERMITO)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: Italy,Switzerland
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2016-12-31
Duration (months): 60.0
Total project cost (EUR): 1499995.2
EU funding (EUR): 1499995.2
Participants: 2
Project status: CLOSED

Organelles are not randomly organized in the cytoplasm of the cell, but often are orderly arranged in mutual relationships that depend on physical, protein bounds. Understanding the molecular nature of the tethers that regulate relative position and juxtaposition of the organelles is one of the main quests of cell biology, given their functional importance. For example, the juxtaposition between mitochondria and endoplasmic reticulum (ER) has been suggested by us and others to crucially impact on Ca2+ signalling and apoptosis. We recently identified the first structural ER-mitochondrial tether in mitofusin 2 (Mfn2), a pro-fusion mitochondria-shaping protein. A fraction of Mfn2 is also located on the ER regulating its morphology, and acting in trans to tether it to mitochondria. The tethering function of Mfn2 impacts on the transmission of Ca2+ signals between the two organelles and is regulated by the oncosuppressor trichoplein/mitostatin. Mfn2 is likely only one of the tethers, as others exist in yeast. Furthermore, the dynamicity of the ER-mitochondria contact is known, but remains poorly understood. Therefore, a clear picture of the anatomy and pathophsyiology of ER-mitochondrial connection is far from being reached. Here we hypothesize that ER-mitochondrial contacts are crucial specialized hubs of cellular signalling whose architecture is modulated by cellular cues, impacting on integrated signalling cascades and ultimately affecting cellular function. To address this hypothesis we wish to setup a research project that aims at (i) increasing our knowledge on the molecular nature of tethers and modulators of ER-mitochondrial tethers in mammalian cells; (ii) clarifying how mitochondrial and ER function are controlled by the tethering; (iii) addressing how juxtaposition influences complex cellular responses including autophagy and cell death; (iv) elucidating the role of tethering in vivo by generating animal models with defined ER-mitochondrial distance.

Keywords: mitochondria,endoplasmic reticulum,fusion,fission,juxtaposition,mitochondria-associated membranes,ca2+ signalling,autophagy
Wiring up visual circuits: Interplay between gene expression and spontaneous and experience-dependent activity (WIRINGVISION)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: Spain
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2017-06-30
Duration (months): 66.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

A fundamental feature of the developing neural circuits is their ability to change in response to sensorial experience. This phenomenon has been particularly observed during the generation of cortical maps, where altering the pattern of sensory experience changes the spatial organization of sensory representations. The mechanisms underlying this form of plasticity include synaptic modification such as long-term potentiation and long-term depression, classically referred to as Hebbian-based rules. Today, there is growing evidence that prior to sensory experience, neural electrical activity plays a role in early brain development. In several developing circuits including retina, spinal cord, hippocampus and cortex, there are transient events that cause these circuits to spontaneously generate waves of correlated activity. However, the cellular and molecular mechanisms that translate these spontaneous activity patterns into mature neural circuits that will eventually be ruled by Hebbian-type plasticity remain largely unknown. The first part of this proposal deals with early events in development in which sensory-independent factors outline a first draft of neuronal connections: How spontaneous activity and molecular factors integrate to shape initial neuronal connectivity? Based in our own findings and using the mammalian visual system as a model, we will genetically silence spontaneous activity in a specific population of neurons and will screen for molecules induced by spontaneous waves. We will also dissect the relative contribution of the different stages of spontaneous waves and will try to understand the relationship of spontaneous activity with different families of axon guidance molecules during the assembly of neural circuits. In the second part of the project we will determine to what extent cortical maps wiring depends on the formation of early thalamic properties and how this wiring may be modified by experience to optimally support information processing.

Keywords: spontaneous activity,sensory-experience activity,visual cortical maps,visual thalamic features,retinal waves
Unraveling the cellular sulfenome: a search for new redox-regulated pathways (SULFENIC)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: Belgium
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-11-01
End date: 2016-10-31
Duration (months): 60.0
Total project cost (EUR): 1492000.0
EU funding (EUR): 1492000.0
Participants: 1
Project status: CLOSED

Within proteins, cysteine residues are sensitive to oxidation by reactive oxygen species (ROS). The first oxidation product of cysteines exposed to ROS is the sulfenic acid derivative (-SOH). Sulfenic acids are highly reactive intermediates that, unless they are stabilized within the protein microenvironment, react with another cysteine present in the vicinity to form a disulfide or are further oxidized to the irreversible sulfinic (-SO2H) and sulfonic (-SO3H) acid modifications. Sulfenic acid formation has traditionally been viewed as an unwanted reaction opening the way to damages that are harmful to proteins. However, it has become clear in recent years that formation of sulfenic acids is not always deleterious to the cell. A new concept is emerging, in which sulfenylation of specific cysteine residues modulates signal transduction pathways by altering the activity and function of cellular proteins, just as phosphorylation and dephosphorylation cycles regulate enzyme activities and cellular pathways. However, the modulation of protein function by sulfenic acid formation has been unambiguously shown for only a few proteins. We postulate that specific oxidation of cysteine residues via sulfenylation modulates the activity of many more proteins and pathways and that numerous sulfenylation sites have not yet been recognized. We want to apply an unprecedented multi-facetted approach to fully grasp the physiological scope of cysteine sulfenic acid formation by uncovering the sulfenome of a living organism, using Escherichia coli as a model. The main objectives of our research program are (1) to comprehensively characterize the sulfenome of E. coli, 2) to identify new proteins and pathways regulated by sulfenylation and (3) to understand how sulfenyla-tion is controlled at the cellular level. If our hypothesis proves to be true, our project will uncover a new “redox dimension” affecting many cellular processes and pathways, opening up new avenues of investigation.

Keywords: sulfenic acid,redox,thioredoxin,escherichia coli,methionine sulfoxide reductase
Molecular mechanisms underlying plant miRNA action (MICROMECCA)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Genetics,Genomics,Bioinformatics and Systems Biology
Countries involved: Denmark
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2016-12-31
Duration (months): 60.0
Total project cost (EUR): 1459011.0
EU funding (EUR): 1459011.0
Participants: 1
Project status: CLOSED

MicroRNAs (miRNAs) are 20-22 nt non-coding RNAs that regulate gene expression post transcriptionally via base pairing to complementary target mRNAs. They have fundamental importance for development and stress adaptation in plants and animals. Although a molecular frame work for miRNA biogenesis, degradation and action has been established, many aspects of this important gene regulatory pathway remain unknown. This project explores four main points. First, we propose to use genetic approaches to identify factors required for translational repression by miRNAs in plants. This mode of action was until recently thought to occur only exceptionally in plants. My post doctoral work showed that it occurs in many miRNA-target interactions. The mechanism remains unknown, however, leaving open a fertile area of investigation. Second, we wish to test specific hypotheses regarding the in vivo role of miRNA mediated endonucleolysis of mRNA targets. Long believed to serve exclusively as a degradation mechanism, we propose to test whether this process could have important functions in biogenesis of long non-coding RNA derived from mRNAs. Third, my postdoctoral work has provided unique material to use molecular genetics to explore pathways responsible for miRNA degradation, an aspect of miRNA biology that only now is emerging as being of major importance. Finally, our unpublished results show that plant miRNAs and their associated effector protein Argonaute (AGO) are associated with membranes and that membrane association is crucial for function. This is in line with similar data recently obtained from different animal systems. We propose to use genetic, biochemical and cell biological approaches to clarify to which membrane compartment AGO and miRNAs are associated, how they are recruited to this compartment, and what the precise function of membrane association is. These innovative approaches promise to give fundamental new insights into the inner workings of the pathway.

Keywords: microrna,gene regulation,plant.
Integrating Post-Abortion Family Planning Services into China's existing abortion service in hospital settings (INPAC)

Framework: FP7 — Cooperation
Programme: Health
Destination: Optimising the delivery of healthcare to European citizens
Action type: Collaborative project
Countries involved: Belgium,China,Denmark,United Kingdom
Call:  (FP7-HEALTH-2011-single-stage, 2011)
Start date: 2012-08-01
End date: 2017-01-31
Duration (months): 54.0
Total project cost (EUR): 3689374.0
EU funding (EUR): 2928384.0
Participants: 7
Project status: CLOSED

In 2008 an estimated 13 million induced abortions were conducted in China. Induced abortions are associated with a high risk of injury or long-term physical and psychological morbidity and a heavy social and economic burden. Most abortions occur in cities and the epidemic affects young and unmarried women as well as rural-to-urban migrant women. The large number of abortions is primarily due to contraceptive failure or no use of contraception. The Chinese Family Planning (FP) program focuses mainly on birth control among married couples and the services are provided by an independent FP system. Young and unmarried women including rural-to-urban migrant women are less likely to access professional FP services. Abortion is a commonly used way to end unwanted pregnancy, however, post-abortion family planning services are often lacking in hospital settings. The INPAC project consortium proposes to integrate post-abortion family planning services into existing abortion services in hospital settings in China and to evaluate the effectiveness of the interventions in terms of reduction of unwanted pregnancies and repeat abortions. Based on the project findings, policy recommendations on health system organization aiming to improve equitable access to reproductive healthcare and FP service will be developed. Context-specific interventions will be developed based on a situation analysis of the effects of the current FP policy and a feasibility assessment of the integration approach. The proposed interventions will be implemented in 30 divisions of mainland China and evaluated with regard to its effectiveness. The project will contribute to standardize the post-abortion family planning services and decrease the long-term costs related to abortion in China. The results of this research will also be of interest to other countries with high abortion rates.

Keywords: health systems,intergration,post-abortion,family planning,health equity,reproductive health,china
Overcome failure to Publish nEgative fiNdings (OPEN)

Framework: FP7 — Cooperation
Programme: Health
Destination: Other Actions across the Health Theme
Action type: Coordination and support actions
Countries involved: Germany,Germany,Spain,United Kingdom,Germany,Croatia,Switzerland,Italy,Germany,France,United Kingdom
Call:  (FP7-HEALTH-2011-single-stage, 2011)
Start date: 2011-11-01
End date: 2013-10-31
Duration (months): 24.0
Total project cost (EUR): 556629.0
EU funding (EUR): 499991.0
Participants: 11
Project status: CLOSED

Full information about completed and ongoing clinical trials is the indispensable base for decision making about medical therapies and diagnostic procedures by patients and doctors. Equally, researchers and research organisations, ethics boards, governments and health system agencies, courts for social justice, pharmaceutical companies and all professional groups of the health care system are dependent on unbiased information. Research projects have consistently shown that for approximately 50% of all launched trials results or reasons for their failure are never published. Not only pharmaceutical industry, but also researchers and their organisations, ethics boards and scientific journals are actively contributing to the general failure to come close to a 100% publication rate. An obvious reason is the complexity of the system as well as the limitation of resources, giving ample space for all stakeholders to avoid appropriate changes and draw attention to deficiencies outside their responsibility. This project is based on the assumption that the existence of broad publication bias with seriously harmful impact has been accepted by all stakeholders and does not require further evidence. The current knowledge on publication bias and its impact will be summarized by systematic reviews of the relevant literature, with emphasis on the situation in the EU. OPEN focuses on the investigation of attitudes and handling of stakeholders involved in the whole knowledge translation process. Surveys, case studies and analyses of policies to reduce publication bias will be conducted to describe the current views and practice of stakeholders who are involved in knowledge translation. These results will be brought together to describe the status quo. Based on those insights recommendations will be derived to reduce publication bias and thus foster the provision of relevant results from clinical trials to citizens and organisations in the EU.

Keywords: publication bias,impact,prevention,negative trials,duplication of research effort