Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Role of chromatin-modifying enzymes in oligodendrocyte precursor state in development and multiple sclerosis (EPIOPC)

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: Sweden
Call:  (FP7-PEOPLE-2012-CIG, 2012)
Start date: 2013-03-01
End date: 2017-02-28
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Oligodendrocytes (OL) are glial cells that mediate myelination of neurons, a process which is defective in multiple sclerosis (MS). Although OL precursors can initially promote remyelination in MS, this process eventually fails. OL precursors (OPCs) go through several epigenetic states during development and MS, which ultimately define their potential to differentiate and myelinate. Transcription factors such as Sox2, Sox10 and Sox9 are key regulators of OL development. However, it is unclear which are their transcriptional mechanisms of action and whether they recruit epigenetic modulators such as chromatin-modifying enzymes (ChMs). In this project, the main objectives are: 1) COMPARATIVE QUANTITATIVE PROTEOMICS OF TRANSCRIPTION FACTOR COMPLEXES We will generate a novel comprehensive library of OPCs representing different epigenetic states during OL development and animal models of MS. We will identify proteins that interact with the transcription factors Sox2, Sox9 and Sox10 in epigenetically distinct OPC populations using SILAC technology, coupled with antibody-based or biotin-based affinity purification strategies and Mass Spectrometry. 2) IDENTIFICATION OF CHROMATIN SIGNATURES AND MOLECULAR MECHANISMS THAT DEFINE EPIGENETIC STATES AND CELL POTENTIAL IN OPCs To determine if the expression/activity of the identified ChMs account for the variation on the differentiation potential of distinct OPCs, we will perform overexpression and RNAi-based screens. In order to assess how the enzymatic activities of the identified proteins modulate OL genes in different OPCs, we will investigate the genome-wide occupancy in OPCs of the identified chromatin-modifiers and associated histone modifications, by Chromatin Immunoprecipitation followed by Next Generation Sequencing. This project will introduce a new perspective into the study of OPC differentiation/myelination, by linking the epigenetic state of the cell with its potential during OL lineage specification and in MS.

Keywords: l208 epigenetics and gene regulation,l506 developmental neurobiology,l502 molecular and cellular neuroscience,l312 stem cell biology,l202 transcriptomics,l203 proteomics,l305 cell differentiation
Misfolded SOD1 Toxicity in Amyotrophic Lateral Sclerosis (MISFOLDED SOD1-ALS)

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: Israel
Call:  (FP7-PEOPLE-2012-CIG, 2012)
Start date: 2013-10-01
End date: 2017-09-30
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease characterized by the loss of upper and lower motor neurons. The reason for the degeneration of motor neurons in ALS is still unknown. Mitochondria have been implicated as a possible target for toxicity by several studies reporting a range of dysfunctions and the toxic binding of misfolded SOD1 to mitochondrial targets. However, the mechanism by which mutant SOD1 associates with mitochondria specifically from affected tissues is still unknown. Preliminary data show that a cytosolic factor in unaffected tissues is responsible for preventing the accumulation of misfolded SOD1. This factor was identified as the macrophage migration inhibitory factor (MIF). MIF inhibits the association of mutant SOD1 with mitochondria and accumulation of misfolded SOD1. The hypothesis of this proposal is that MIF is reduced in abundance or inactive as a chaperone within the CNS, leading to increased accumulation of misfolded SOD1 and neurodegeneration. This proposal aims to unambiguously determine how toxicity is caused by misfolded SOD1 accumulation and finally an attempt to rescue these toxic effects in models of ALS will be done. The specific aims are (1) Determination of the tissue specificity of misfolded SOD1 accumulation and mitochondrial association and characterization of MIF activity as a chaperone for misfolded SOD1; (2) Determination of how mitochondrial association of misfolded SOD1 affects mitochondrial function in the spinal cord of mutant SOD1 animals; and (3) Determination of whether increased synthesis or depletion of MIF affects misfolded mutant SOD1 accumulation and pathogenesis in mice. The proposed study has the potential to yield important information about misfolded SOD1 toxicity mechanisms. Moreover, the characterization of MIF as a novel chaperone for misfolded SOD1 opens new avenues for the development of ALS therapies.

Keywords: l511 neurological disorders,als,misfolded protein,sod1,mitochondria,neurodegeneration,motor neurons
Permafrost Carbon Cycle Observations and Modeling across multiple spatiotemporal scales (PERCCOM)

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: Germany
Call:  (FP7-PEOPLE-2012-CIG, 2012)
Start date: 2013-03-01
End date: 2017-02-28
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Permafrost ecosystems in the high Northern latitudes are estimated to store about 1700 Petagram of carbon, which is roughly 50% of the total global belowground carbon, or about double the amount currently contained in the global atmosphere. Future climate projections indicate a strong warming potential for these regions over the next century, which may significantly alter the biogeochemical processes governing the carbon cycle, and thus holds the potential to partly destabilize and release these enormous existing carbon reservoirs. At the same time, the database on carbon exchange fluxes between surface and atmosphere is sparse compared to the size of the region, and significant gaps exist concerning e.g. the coverage of specific landscape units, or observations during the cold season. As a consequence, many processes within the permafrost carbon cycle remain poorly understood, leading to large uncertainties in climate model simulations for this region. To close existing gaps in both flux Arctic flux databases and process understanding, integrated monitoring and modeling tools are required that provide insight into feedback mechanisms between permafrost ecosystems and climate change. This project will establish year-round observation systems in the permafrost region that integrate over multiple spatiotemporal scales to capture carbon flux variability from local to continental levels. The obtained information will be used to identify causal links between environmental drivers and patterns in carbon fluxes based on an integrated framework of atmospheric transport modeling, multivariate statistics, geostatistical inversion and biogeochemical process modeling. The resulting insights into biogeochemical mechanisms will help to improve process representation in modeling frameworks, with the overarching objective to reduce uncertainties in climate projections.

Keywords: v201 terrestrial ecology - land cover change,v201 biogeochemistry - biogeochemical cycles - environmental chemistry,v201 meteorology - atmospheric physics and dynamics
Cellular composition of the pancreas: elucidating the role of mesenchymal signaling pathways (EMPANMES)

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: Israel
Call:  (FP7-PEOPLE-2012-CIG, 2012)
Start date: 2013-03-01
End date: 2017-02-28
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

The pancreas constitutes of various cell types with distinctive function. Exocrine cells produce and secrete digestive enzymes while endocrine cells, including insulin-producing beta-cells, secrete hormones that regulate glucose homeostasis. The proportional quantity of the different pancreatic cell populations is well defined, when exocrine cells encompass majority of the tissue mass. However, while the establishment of pancreas cellular composition during embryogenesis has been well acknowledged, its regulation is far from being elucidated. While cell intrinsic cues were shown to influent this process in the developing pancreas, the role of extrinsic signals is less understood. I hypothesize that extrinsic cues define the rate of cell proliferation and therefore govern the sizes of various pancreatic cell populations in vivo. Here I will use a novel transgenic mouse model I have recently developed, the Nkx3.2-Cre mouse line, as a tool to evaluate extrinsic roles in the regulation of pancreas cellular composition. I will further use this tool to elucidate the extrinsic cues playing a role in this process. To this end, I will deregulate signaling pathways in the pancreatic mesenchyme, a key component of the embryonic pancreas microenvironment. I will focus on two such pathways, the Hedgehog and the Wnt pathways, which are required for normal mesenchymal gene expression. I expect their deregulation will hamper mesenchymal ability to promote appropriate pancreatic cellular composition, and will enable the identification of extrinsic cues required for this process. The findings of this study will allow better understanding of the extrinsic requirements during pancreas development, and the cues governing its cellular composition. Furthermore, this study will aid current affords to expand beta-cells upon will, as a potential cure to diabetes.

Keywords: pancreas,pancreas organogenesis,mesenchyme,mesenchymal-epithelial interactions,cell population size,mouse embryo,l309 developmental genetics - embryology in animals
Exact Methods in Gauge and String Theories (EMGST)

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: Ireland
Call:  (FP7-PEOPLE-2012-CIG, 2012)
Start date: 2013-03-01
End date: 2017-02-28
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Much of the structure of the world around us is currently understood in the language of quantum field theory. As such theories have been highly tested by experiment we have a great deal of confidence that they are correct, at least in their regimes of applicability. However, to answer many of the most important open questions, from the nature of confinement to the origin of high temperature superconductivity, we need to develop new tools to find exact, non-perturbative results. For specific gauge theories we can understand their strongly coupled behaviour by making use of their dual description in terms of certain quantum theories of gravity – the so-called gauge/gravity duality. The paradigmatic example is the conjectured duality between four dimensional maximally supersymmetric Yang-Mills and strings on a curved space-time, five dimensional anti-de Sitter space. Recently, the discovery that this example of the gauge/gravity duality is integrable, i.e. that there are an infinite number of hidden conserved quantities, in the planar limit has led to a great deal of progress, for example providing exact results for the anomalous dimensions of all operators. In the proposed project the origin and structure of this integrability is to be considered with an eye to developing tools to calculate further interesting observables at all values of the coupling. In particular, extending the techniques of integrable models to the calculation of three-point functions would, in principle, give a complete determination of the planar theory. It is also proposed to study a wider class of observables and, for example, the exact form of planar scattering amplitudes, which are related to higher point correlation functions, is an open problem whose solution may well be within our theoretical grasp. Furthermore, the methods and results will be generalised towards other, more phenomenologically relevant, theories.

Keywords: string theory,gauge theory,ads/cft,integrable structures.
Structural targeting of PI4 kinases (STARPI4K)

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: Czechia
Call:  (FP7-PEOPLE-2012-CIG, 2012)
Start date: 2013-03-01
End date: 2017-02-28
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Phosphatidyl inositol phosphates (PIPs) are biosynthesized from phosphatidyl inositol (PI) by the action of PI kinase. The phosphatidylinositol 4-phosphate (PI(4)P) is produced by the action of phosphatidylinositol 4-kinase (PI4K). PIPs are universal markers of intracellular membranes. Their precise spatial and temporal resolution control enables various protein machineries to operate in the correct location at the exact time. PI(4)P is the single most abundant mono phosphoinositide and is the marker of the Golgi and the trans-Golgi network (TGN). It has been reported to play a key role in membrane biogenesis, vesicular transport, lipid dynamics, and protein and lipid sorting in the TGN. Importantly, the replication of several plus RNA viruses, mainly the Hepatitis C virus (HCV), SARS, and poliovirus (PV) depend on PI(4)P. For instance, HCV hijacks PI4K III alpha to generate endoplasmatic reticulum (ER) derived membranous webs that are enriched in PI(4)P and where the replication of HCV takes place. The main goals of this proposal are (i.) to get structural insight into PI(4)P biosynthesis by solving crystal structure of the PI4K kinase domain and/or the full length enzyme (ii.) to solve the crystal structure of the kinase domain in complex with a small molecule inhibitor like the well known PIK93 (iii.) use the structural information to design novel small molecule inhibitors with higher affinity and specificity that could be used as antivirals.

Keywords: kinase,crystal structure,phosphatidyl inositol phosphate,inhibitor,hepatitis c virus
Optimizing Antisense Oligonucleotides for Efficient and Specific Knockdown of Nuclear Non-Coding RNA (NONCODOWN)

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: United Kingdom
Call:  (FP7-PEOPLE-2012-CIG, 2012)
Start date: 2013-06-01
End date: 2017-05-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

The past decade has seen a dramatic increase in discovery of noncoding RNA with functional regulatory roles in the nucleus of mammalian cells. Yet tools to manipulate these nuclear noncoding RNAs remain inadequate. This proposal will develop optimized antisense oligonucleotides for targeting and degrading structured RNAs in the nucleus. This will be carried out by using both the best of what already exists in the field of nucleic acid chemistry (e.g. locked nucleic acid and the gapmer approach) and innovative new designs (e.g. CuAAC-derived PNA-DNA-LNA chimeric oligomers for degrading structured RNA targets).

Keywords: c134 biological chemistry,oligonucleotides,noncoding rna,antisense,gene silencing,cell nucleus,knockdown,enhancer rna,dna,lna,pna,cuaac,huisgen,click chemistry
Study of the ElectroWeak Symmetry Breaking and the Higgs Sector with the ATLAS detector at the LHC (EWSB)

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: United Kingdom
Call:  (FP7-PEOPLE-2012-CIG, 2012)
Start date: 2013-04-01
End date: 2017-03-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

The Standard Model (SM) of particle physics is the most successful physical theory to date. Its main phenomenology has been confirmed, and it has withstood quantitative test of unprecedented precision in various facilities for 30 years now. Its only piece lacking direct experimental observation is the mechanism of electroweak symmetry breaking, providing with mass the weak gauge bosons and it is related to the appearance of the SM Higgs boson. Following the observation of a new particle by ATLAS and CMS experiments at the CERN Large Hadron Collider (LHC) in summer 2012, the SM is possibly completed. With the current experimental precision, the new particle production and decay patterns are compatible with those of the SM Higgs boson. To unambiguously characterize this new particle, detailed studies of its properties (mass, production rates, spin/CP quantum numbers, self-couplings) are needed, while searches for other similar particles are important. Deviations from the SM expectations or new particles, would be direct observation of new physics phenomena. These studies are currently the highest priority items in the particle physics agenda. The proposed research will use the experience on the searches in the H->ZZ(*)->4l final state, to provide answers to these questions. This final state, although it has low event rates, is ideal for such studies because it is fully reconstructed with high precision and offers the best signal-to-background ratio in the LHC. By 2017, it will provide the best single channel mass measurement. The measurement of production rates at exclusive final states, enhancing specific production mechanisms (vector-boson fusion, associated production with a vector boson), will be invaluable for the study of the couplings. For spin/CP, it will dominate the sensitivity for a graviton-like resonance and will put stringent limits on potential CP-violating components. Finally, it will dominate the searches for additional similar heavy particles.

Keywords: p101 fundamental interactions and fields,p102 particle physics,higgs boson,higgs mechanism,electroweak symmetry breaking,standard model,beyond the standard model,new physics
Energy Efficiency in the Supply Chain through Collaboration, Advanced Decision Support and Automatic Sensing (E-SAVE)

Framework: FP7 — Cooperation
Programme: Information and Communication Technologies
Destination: ICT for a low carbon economy
Action type: Collaborative project
Countries involved: Luxembourg,Greece,Italy,Switzerland,Austria,Germany,Germany,Cyprus,Belgium
Call:  (FP7-ICT-2011-7, 2011)
Start date: 2012-01-01
End date: 2014-06-30
Duration (months): 30.0
Total project cost (EUR): 3640888.0
EU funding (EUR): 2520000.0
Participants: 11
Project status: CLOSED

The e-SAVE project aims to contribute to an energy-efficient supply chain by providing the system, services, collaboration platform and management tools that will help companies monitor, manage and share energy use and carbon footprint data in order to support operational as well as strategic decision making and supply chain design decisions. The project will specifically focus on the consumer goods sector, by involving the ECR Europe organisation, representing all major manufacturers and retailers in this sector, as well as one of its active members, Barilla, who pioneers in environmental sustainability practices. Emphasis is placed on industry adoption and quantifiable impact assessment. The e-SAVE technical approach relies on an interoperable information infrastructure that integrates ERP systems with automatic data capturing technologies (mainly smart energy meters and unique product identification technologies) in order to support generic components for energy efficiency monitoring and life cycle assessment; upon these e-SAVE deploys new optimization algorithms for energy-efficient supply chain operations, simulation models and tools for strategic supply chain design decisions and dynamic energy-efficiency product labelling. The project will further build on existing market-leading tools owned by the e-SAVE partners in the fields of energy-monitoring, life-cycle assessment and simulation. Contribution to information sharing standards and energy efficiency ontologies will also be sought. Overall, the e-SAVE project aims to deliver a modular and extensible information, collaboration and management support infrastructure that not only captures the data required for effectively monitoring energy use and other environmental measures, but also provides the management tools that utilize this information and support decisions and every day operations for reducing energy consumption and carbon emissions in a feedback loop.

Keywords: energy efficiency monitoring,supply chain management,life cycle assessment,product energy profile,simulation and decision support,energy-efficiency product labelling,automatic data capturing