Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
CHEMometric and High-throughput Omics Analytical Methods for Assessment of Global Change Effects on Environmental and Biological Systems (CHEMAGEB)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Physical and Analytical Chemical sciences
Countries involved: Spain,Spain
Call:  (ERC-2012-ADG_20120216, 2012)
Start date: 2013-04-01
End date: 2018-03-31
Duration (months): 60.0
Total project cost (EUR): 2454280.0
EU funding (EUR): 2454280.0
Participants: 2
Project status: CLOSED

We propose to develop new chemometric and high-throughput analytical methods to assess the effects of environmental and climate changes on target biological systems which are representative of ecosystems. This project will combine powerful chemometric and analytical high-throughput methodologies with toxicological tests to examine the effects of environmental stressors (like chemical pollution) and of climate change (like temperature, water scarcity or food shortage), on genomic and metabonomic profiles of target biological systems. The complex nature of experimental data produced by high-throughput analytical techniques, such as DNA microarrays, hyphenated chromatography-mass spectrometry or multi-dimensional nuclear magnetic resonance spectroscopy, requires powerful data analysis tools to extract, summarize and interpret the large amount of information that such megavariate data sets may contain. There is a need to improve and automate every step in the analysis of the data generated from genomic and metabonomic studies using new chemometric and multi- and megavariate tools. The main purpose of this project is to develop such tools. As a result of the whole study, a detailed report on the effects of global change and chemical pollution on the genomic and metabonomic profiles of a selected set of representative target biological systems will be delivered and used for global risk assessment. The information acquired, data sets and computer software will be stored in public data bases using modern data compression and data management technologies. And all the methodologies developed in the project will be published.

Keywords: chemometrics,metabonomics,genomics,toxicology,nmr,gc-ms,lc-ms,dna chips
From Cells to Organs on Chips: Development of an Integrative Microfluidic Platform (CELLO)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Condensed matter physics
Countries involved: France
Call:  (ERC-2012-ADG_20120216, 2012)
Start date: 2013-07-01
End date: 2018-06-30
Duration (months): 60.0
Total project cost (EUR): 2260000.0
EU funding (EUR): 2260000.0
Participants: 1
Project status: CLOSED

We shall develop a microfluidic and microsystems toolbox allowing the construction and study of complex cellular assemblies (“tissue or organ mimics on chip”), in a highly controlled and parallelized way. This platform will allow the selection of specific cells from one or several populations, their deterministic positioning and/or connection relative to each other, yielding functional assemblies with a degree of complexity, determinism and physiological realism unavailable to current in vitro systems We shall in particular develop “semi-3D” architectures, reproducing the local 3D arrangement of tissues, but presenting at mesoscale a planar and periodic arrangement facilitating high resolution stimulation and recording. This will provide biologists and clinicians with new experimental models able to bridge the gap between current in vitro systems, in which cells can be observed in parallel at high resolution, but lack the highly ordered architecture present in living systems, and in vivo models, in which observation and stimulation means are more limited. This development will follow a functional approach, and gather competences and concepts from micr-nano-systems, surface science, hydrodynamics, soft matter and biology. We shall validate it on three specific applications, the sorting and study of circulating tumour cells for understanding metastases, the creation of “miniguts”, artificial intestinal tissue, for applications in developmental biology and cancerogenesis, and the in vitro construction of active and connected neuron arrays, for studying the molecular mechanisms of Alzheimer, and signal processing by neuron networks. This platform will also open new routes for drug testing, replacing animal models and reducing the health and economic risk of clinical tests, developmental biology , stem cells research. and regenerative medicine.

Keywords: microfluidics,lab-on-chips,cellular interactions,cell biology,molecular and cellular neuroscience,neurological disorders,synthetic biology,stem cells
Development Of Scintillator-Based Fast-Ion Loss Detectors For Fusion Devices Using Low-Energy Particle Accelerators (FILDDEV)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Life-long training and career development
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2012-CIG, 2012)
Start date: 2012-09-01
End date: 2016-08-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Magnetohydrodynamic (MHD) instabilities are ubiquitous in laboratory as well as in astrophysical plasmas. Their interplay with energetic (suprathermal) ions is of crucial importance to understand the energy and particle exchange in astrophysical plasmas as well as to obtain a viable energy source in magnetically confined fusion devices such as ITER. Experimentally, a detailed knowledge of the wave-particle interaction can be gained from direct measurements of MHD induced fast-ion losses in fusion plasmas. The principal diagnostics to obtain this information in a magnetic fusion device are scintillator based fast-ion loss detectors (FILD) that are located at the plasma edge. A scintillator based FILD acts as a magnetic spectrometer, dispersing the measured escaping fast-ions onto a scintillator, with the strike points depending on their gyroradius (energy) and pitch angle (angle between ion velocity and magnetic field line), thus, giving the full information of the velocity space of the escaping ions at the detector position. The research lines proposed here for the next years aim at gaining a better understanding of the energetic particle acceleration / transport mechanisms induced by MHD fluctuations through innovative diagnosis techniques developed at CNA (Centro Nacional de Aceleradores) and employed in large fusion devices. We plan to exploit the CNA low-energy particle accelerators to develop and calibrated fusion-relevant charged particle detectors as well as to explore new techniques. New radiation hardness scintillator materials with high efficiency against fusion-relevant charged particles and short decay time will be developed and characterized. A natural result of this activity will be a flexible Ion Beam Analysis (IBA) chamber for fusion technology installed at the CNA Tandem and Cyclotron with equipment suited for ionoluminescence (material/photonic) studies, a facility unique in Spain and rare in Europe.

Keywords: p105 gas and plasma physics,p103 nuclear physics
Nuclear Envelope Biogenesis, Function and Dynamics (NUCENV)

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: Switzerland
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-04-01
End date: 2018-03-31
Duration (months): 60.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 1
Project status: CLOSED

The nuclear envelope (NE) harbors key roles in cellular and organismal homeostasis, reflected by a variety of diseases caused by mutations in NE proteins. Despite the fundamental role of the NE in protecting and organizing the genome, still little is known about the molecular mechanisms underlying NE biogenesis, dynamics and functionality. We will address 3 open questions in NE biology, using vertebrate cells as model system. (1) To understand how the functional specification of the NE by transmembrane proteins is generated, we will decipher how membrane proteins are sorted to the inner nuclear membrane (INM). To reach this goal, we will define targeting signals and the mode of NPC passage of INM proteins, and identify the molecular requirements for transport. (2) Based on structural analysis, we will investigate how the molecular organization of LINC complexes, which are formed by interacting pairs of SUN and KASH proteins spanning the NE, determines their role in NE architecture and as tethers of the NE to the cytoskeleton. (3) We will study dynamic changes of the NE that occur at the onset of ’open’ mitosis, when the nuclear compartment is disintegrated to allow for the formation of a cytoplasmic mitotic spindle. NE breakdown (NEBD) presents a dramatic change of cellular architecture and comprises a series of events including disassembly of nuclear pore complexes, the nuclear lamina and retraction of NE membranes into the endoplasmic reticulum. To elucidate the molecular mechanisms controlling and executing these steps of nuclear disassembly, we will characterize the cellular machinery involved in NEBD and unravel the molecular function of identified components. All these questions will be addressed by a blend of in vivo approaches relying on high-end fluorescence imaging linked to computational image analysis, RNAi screening, as well as powerful in vitro systems recapitulating protein transport to the INM or NEBD that we have developed, and biochemical methods.

Keywords: nuclear envelope,mitosis,npc,nucleoporin,inner nuclear membrane,protein sorting,linc,protein modification,kinase,spindle
Integrin: signalling from the tail and the hub (SIGNAL2THEHUB)

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: 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): 2462689.0
EU funding (EUR): 2462689.0
Participants: 1
Project status: CLOSED

Integrin-mediated cell adhesion is essential for the development and homeostasis of multicellular organisms. Integrins are ubiquitously expressed heterodimeric adhesion receptors consisting of α and β subunits. They exhibit two striking properties; they can regulate their affinity for ligands and assemble large signalling hubs called adhesomes. Both properties depend on the α and β cytoplasmic tails; when integrins switch from inactive to active conformations their weakly associated tails separate and recruit adhesion proteins leading to adhesome assembly. How active integrins revert to the inactive state, and how the weak α/β tail association is maintained is largely unknown. The mechanistic contribution of individual integrin classes to the recruitment of proteins to the adhesome and how adhesome signalling is induced is also unclear. In this proposal we will address these fundamental questions in 4 specific aims. In the first aim we will identify proteins that keep integrin tails associated and define the roles of their tail binding with respect to integrin inactivation and turn over. In the second aim we will utilize high-resolution quantitative mass spectrometry to define how different integrins assemble adhesomes with common and specific components that signal in highly regulated manners. Our third aim will determine how integrin tails nucleate an adhesion complex that expedites further interactions with multiple binding partners by performing crosslinking proteomics of adhesion proteins bound to different β integrin tails in vitro. In the fourth aim we will use genetically engineered mice to determine how ubiquitously expressed proteins of the adhesome perform organ- and cell type-specific functions. Completion of these aims will help define the fundamental mechanisms whereby integrins control their complex signalling networks. This has implications for our understanding of development and disease as integrins play key roles for almost all cellular functions.
A radical approach for improved glaucoma treatment. (OCULUS)

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: Ireland,United States
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-04-01
End date: 2018-09-30
Duration (months): 66.0
Total project cost (EUR): 2499838.0
EU funding (EUR): 2499838.0
Participants: 2
Project status: CLOSED

Open angle glaucoma (OAG) is the second leading cause of world blindness. Treatments involving topically applied pressure-reducing medications or surgery targeting ocular drainage channels are effective, although significant complications exist. We propose to address the hypothesis that it is possible to develop a radical approach to management of intraocular pressure employing an AAV-mediated system for increasing the permeability of Schlemm’s canal endothelial cells (SCEC), based on published supportive data from this laboratory showing that RNAi-mediated down regulation of mRNA encoding components of tight junctions of neuronal vascular endothelia induces increased cell permeability, a process which has been used to validate a procedure for acute treatment of neuronal edema. While tight junctions of neuronal vascular endothelial cells have been extensively studied and comprise of a series of up to 30 protein components, less is known of the organization of adherence mechanisms of SCEC, although electron- and immunofluorescence microscopy show the presence of tight junctions. We propose a comprehensive analysis of tight junction protein expression in SCEC in vitro. In vivo studies will involve introduction of AAV vectors into the anterior chamber of the eye in rodent models of elevated IOP. The vectors will be designed to express shRNAs targeting a variety of tight junction transcripts expressed in SCEC using an inducible system. The effect of RNAi-mediated increase in the permeability of SCEC will be assessed using aqueous humour outflow measurement methods and we will also explore the utility of high resolution and diffusion-weighted MRI for this purpose, which may prove to be a simpler, non-invasive and clinically relevant method. This research will provide further fundamental insights into the mechanisms of ocular pressure maintenance and could provide benefit to those patients not responsive to conventional means of therapy.

Keywords: glaucoma,rnai therapy.
Common molecular pathways in epithelial-mesenchymal transition and left-right asymmetries (EMTASY)

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: Spain
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-05-01
End date: 2018-12-31
Duration (months): 68.0
Total project cost (EUR): 2460000.0
EU funding (EUR): 2460000.0
Participants: 1
Project status: CLOSED

The majority of animals show an external bilateral symmetry, precluding the observation of multiple internal left-right (L/R) asymmetries which are fundamental for organ packaging and function. A prominent molecular pathway converging on and downstream of the Pitx2 transcription factor confers left-handed information in the left side of the embryo, with players expressed on the right ensuring that the left determinants are excluded. Therefore, conferring or excluding left identity in left and right hand sides, respectively, drives L/R asymmetry. Some indications suggest that a program actively specifying right–handed information could exist on the right. Our recent findings support this view. In a screening for novel regulators of the epithelial to mesenchymal transition (EMT), we have identified a transcription factor, EMT2, which similarly to well known factor Snail, it is an EMT inducer. The EMT is crucial for the development of tissues during embryonic development and for the progression of carcinomas to the invasive state. Strikingly, again as Snail, in addition to promote EMT, the EMT2 factor is predominantly expressed on the right side and may operate instructing L/R identity on the right-hand side of the embryo. With this background, our knowledge of the EMT and a series of genome-wide high-throughput approaches and a comprehensive functional analysis using the chick, the fish and the mouse as model systems we propose to reveal the putative molecular pathways conveying right-handed information and to reveal commonalities between L/R pathways and the EMT. In the long run, we aim at better understanding human pathologies that involve these morphogenetic and cellular processes, including pathological situs conditions (i.e. altered organ positioning) and cancer progression.

Keywords: cell adhesion,cell movements,epithelial to mesenchymal transition,quirality,left-right asymmetry
Randomized controlled trial of metformin and dietary restriction to prevent age-related morbid events in people with metabolic syndrome (MEMEME)

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: Italy
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-08-01
End date: 2019-07-31
Duration (months): 72.0
Total project cost (EUR): 2499999.6
EU funding (EUR): 2499999.6
Participants: 1
Project status: CLOSED

Age–related chronic diseases (ArCD) are complex non-linear processes that depends on a large number of interconnected genetic and metabolic pathways which should be tackled with a many faceted preventive strategy. Calorie-dense diet and sedentary lifestyle are responsible of the growing prevalence of metabolic syndrome (MetS), which, together with tobacco, is the major preventable cause of ArCD, mediated by the increased availability of insulin, growth factors, and inflammatory cytokines. In animals, calorie restriction (CR) is the most potent dietary intervention for preventing ArCD and prolonging life. In humans, we and others have shown that a sustainable CR, resulting in decreased prevalence of MetS, can be obtained through a comprehensive change in dietary habits, reducing animal food and refined carbohydrates, and increasing whole grain cereal products, legumes and vegetables, according to the Mediterranean and macrobiotic diet principles. Metformin (MET), an antidiabetic drug associated with decreased cancer incidence, activates the same gene pathways activated by CR, including AMPK/TSC, which reduces energy consuming processes, and cell proliferation (through the inhibition of mTOR). We propose a placebo controlled randomised trial to test whether treatment with MET, with or without associated CR, reduces the incidence of major chronic diseases, such as cancer, myocardial infarction, stroke, and diabetes. We estimated that randomizing 2,000 women and men aged 55-74 at high risk of developing ArCD because of MetS, shall provide over 90% power (at alpha = 0.05) to detect a significant 25 to 33% reduction of ArCD incidence in 5 years. In a subsample of the cohort we shall study the genetic and epigenetic mechanisms of the preventive action of metformin and CR.

Keywords: metformin,mediterranean diet,metabolic syndrome,calorie restriction
Signalling compartmentalization and vesicle Trafficking at the Phagocytic Synapses (STEPS)

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: Italy
Call:  (ERC-2012-ADG_20120314, 2012)
Start date: 2013-04-01
End date: 2019-03-31
Duration (months): 72.0
Total project cost (EUR): 2350342.0
EU funding (EUR): 2350342.0
Participants: 2
Project status: CLOSED

A key feature of the immune response is its specificity and macrophages must be able to discriminate precisely between an infectious stimulus and a non-infectious one and tune their response in accordance with the molecular context in which the target particle is recognized. In recent years, scientists have proposed the concept of the phagocytic synapse, to stress the fact that a particle does not engage only one receptor on the cell surface; instead, an array of receptors interacts with a specific pathogen, either sequentially or simultaneously. Indeed, the tightly controlled and specific responses of macrophages require the establishing of checkpoints for signalling and the phagocytic synapse represent an exquisite site for cross-talk among several signalling pathways. Although we can describe detailed signalling pathways for most of the single receptors acting at the phagocytic synapse, we still do not know how these pathways are integrated during the various phases of macrophage responses. An integrated view of phagocytic synapse signalling would allow us to understand the contribution of each ligand-receptor pair to macrophage dysfunctions in pathology and to design novel immunotherapeutic strategies. The aim of STePS is to provide a deeper understanding of the molecular interactions leading to the orchestration of phagocytic synapses for phagocytosis and activation, two events crucial for immune responses to pathogens as well as for inflammation. In particular, we will focus on three fundamental aspects that bring together the fields of immunology and cell biology: establishment of dynamic platforms for recognition and signalling at the plasma membrane; vesicle trafficking to the plasma membrane; signalling compartmentalization for specific cell functions. Importantly, these mechanisms will be analyzed in the context of physiological and pathological conditions, thus providing answers to both basic and translational biomedical research questions.

Keywords: signaling compartmentalization,vesicle trafficking,chronic inflammation,obesity