Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Regulation of iron homeostasis through beta-amyloid precursor processing in neuronal health and disease. (APP & IRON TRANSPORT)

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: 2013-03-01
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 life essential element iron is required as a cofactor in central nervous system metabolic processes, but unbound iron catalyzes the production of toxic reactive oxygen species. Neuronal iron accumulation is a common pathological feature in the cortex in Alzheimer’s disease (AD), the substantia nigra (SN) in Parkinson’s disease (PD), and the tauopathies. Since too much or too little iron can compromise cell viability, cellular iron homeostasis is tightly regulated. Ferroxidases, oxidize Fe2+ to Fe3+, and are essential for maintaining intracellular iron homeostasis. A deficiency in the surface presented ferroxidase leads to toxic iron accumulation and degeneration. Ferroxidase activities in the brain may fail with aging and a range of neurodegenerative disorders (ND), possibly contributing to disease pathogenesis. My group has discovered that the ferroxidase activity of β-amyloid precursor protein (APP) is essential for neuronal iron efflux and inhibited APP ferroxidase activity parallels iron accumulation in some ND. Disruption in the correct localization of a ferroxidase may be fundamental in the disease process. Of relevance, neuronal anterograde transport of APP requires tau and we have recently shown decreased tau expression impairs the presence of cell surface APP leading to inefficient efflux of iron and intensifying the risk of excitotoxicty within the region via intraneuronal iron accumulation. Primary aims will elucidate the role of APP trafficking and processing on iron efflux regulation within general neurobiology and investigate this mechanism in iron accumulating age- and pathologically- affected neurons already known to have problems with APP, tau and excitotoxicity. Some current therapeutic compounds for ND are proposed to work via restoring metal homeostasis. A final aim will determine if these compounds, as well as a number of novel derivatives, work through a pathway that restores APP to its correct function in neuronal iron efflux.

Keywords: l302 cell biology and molecular transport mechanisms,l502 molecular and cellular neuroscience,l511 neurological disorders
Role of the mitochondrial anti-viral signaling protein in sepsis (MAVS)

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

Severe sepsis is an important complication of infections and one of the leading causes of morbidity and mortality. For the countries of the European Union it is estimated that approximately 600,000 cases and more than 150,000 deaths occur from sepsis per year. Currently, no approved treatment options are available for the therapy of septic shock in humans. This research proposal intends to investigate the acute inflammatory response during experimental sepsis in rodents. Our preliminary data indicate an essential role of the novel ‘mitochondrial anti-viral signaling protein’ (MAVS) during sepsis. Mice with genetic deficiency of MAVS appear to be protected against sepsis. We seek to study, how the effects of MAVS are related to regulation of cytokines, innate and adaptive immune cells, apoptosis, abnormalities in blood coagulation and appearance of cytotoxic factors in the context of experimental sepsis. Such studies will be useful to identify novel molecular mechanisms during sepsis which could ultimately be utilized for the development of effective treatment strategies for sepsis.

Keywords: innate immunity,sepsis,macrophages,interleukin-27,cytokines,coagulation
Narrating the Past in the Hindu Himalayas: On Social Memory in South Asian Oral Traditions (NPHH)

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 Eurocentric notion of South Asian Hindu society as intrinsically ahistorical due to its perception of time as cyclical has resulted in more than two centuries of misreading of Indian traditions. While this misperception has been viewed with increasing suspicion in recent decades, the scholars who attempt to read Indian texts with the aim of deciphering indigenous perceptions of the past remain few. This project seeks to redress this lacuna by compiling, translating and analyzing a corpus of oral traditions from the West Himalayas that shall be investigated in light of recent theories of Social Memory. The project shall further draw upon Anthropology, History and Oral Literature to explore the ways Himalayan communities preserve, appropriate and manipulate shared experiences from their past to assert collective identities in the preset, thereby contributing to the multidisciplinary study of Social Memory and broadening its scope to include that of Himalayan Studies. * Please note that the correct title of this project is 'Narrating the Past in the Hindu Himalayas: On Social Memory in South Asian Oral Traditions' and NOT 'Cultural History of the West Himalayas', which was a provisional title used to log into the EPSS system, but which I was subsequently unable to change.

Keywords: social memory,himalayas,hinduism,oral history,epic traditions,anthropology,south asia,historiography
Roles of astrocytes in synaptic transmission and plasticity (ASTROSYN)

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: France
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 research area of this proposal is Life Science at the intersection of neuroscience, pharmacology and physiology. In the central nervous system (CNS), astrocytes are both numerous and complex. They contact most other cell types in the CNS, and the processes of a single astrocyte can envelop as many as 140,000 synapses. Thus, these cells are uniquely able to receive signals from many sources, in particular synapses, via their G protein-coupled receptors (GPCRs). Additionally, using conventional pharmacological approaches, it has suggested that astrocytes can also send signals to neurons by release of various transmitters to modulate synaptic transmission and plasticity. This reciprocal signaling between neurons and astrocytes (gliotransmission) is still a novel concept, and its physiological relevance remains controversial in the field. In the first part of this proposal, we propose to use novel pharmacogenetic tools that will allow us to selectively activate astrocytes vs. neurons in a more physiological manner to further test the concept of gliotransmission and its role in sleep and memory in vivo. In the second part of this proposal, we will take advantage of these powerful pharmacogenetic tools to test a hypothesis that has heretofore been inaccessible to experimentation, i.e., the possibility that astrocyte GPCRs control glycogen metabolism to modulate synaptic transmission, plasticity, sleep and memory formation. Addressing successfully such major questions in the field of neuroscience, and in particular, resolving some controversies about gliotransmission has profound implications in our understanding of the brain, but also and importantly ,in the clinic. From these studies, we are likely to resolve important aspects of astrocyte function and open up entirely new areas of investigation; this work may lead to potential treatments of diseases, including Alzheimer disease and memory and sleep disorders.

Keywords: neuroscience,pharmacogenetics,physiology,gpcr,neuron-glia interactions,sleep,memory,synaptic transmission,plasticity,metabolism,ca2+,in vivo
Sexual selection - How is variation maintained? (SEX SEL - VAR)

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: Netherlands
Call:  (FP7-PEOPLE-2012-CIG, 2012)
Start date: 2013-09-01
End date: 2017-12-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Across the animal kingdom, striking displays and ornaments are produced by sexual selection. Current thinking is that females choose the most elaborate males because they display genetic benefits to offspring. However, this should lead to a rapid decline in genetic variation within species. Variation between individuals is the raw material upon which selection acts, so how is this variation maintained? Solving this ‘paradox of the lek’ continues to be one of the most contentious issues in evolutionary ecology. This proposal suggests that three important factors have been overlooked in the study of sexual selection. First, individual differences in mate preference function for direct verses indirect benefits are expected to vary with the choosers own phenotype, and thus serve to maintain variation within populations. Second, mutual mate choice has been neglected, and sex specific optima are expected to play a key role. Third, non-genetic parental effects are closely linked with mate preference and have huge implications for selection, but such effects are rarely considered in this context. I propose to test how these factors influence variation using an established population of wild great tits, which are amenable to carefully controlled lab and field experiments. I will complement phenotypic studies with state-of-the-art SNP genotyping and modeling techniques to determine how the heritability of shared traits and preference functions, and selection for heterozygosity affect genetic variation. This uniquely integrative approach will answer a fundamental question in evolutionary biology: How is genetic variation maintained by sexual selection? The answer to this question is key to our understanding of evolutionary processes, the likelihood of extinction and speciation, as well as animal breeding.

Keywords: sexual selection,maternal effects,variation,great tit,mate preference function
Systems Imaging of Emerging Asymmetry in Vertebrate Development (SIEAVD)

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: Switzerland
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

There is a long-running controversy about how early cell fate decisions are made in the developing mammalian embryo. In particular, it is controversial when the first events that can predict the establishment of the pluripotent and extra-embryonic lineages in the blastocyst occur. It has long been proposed that the position and polarity of cells at the 16- to 32-cell stage embryo influence their decision to either give rise to the pluripotent cell lineage that eventually contributes to the inner cell mass (ICM), comprising the primitive endoderm (PE) and the epiblast (EPI), or the extra-embryonic trophectoderm (TE) surrounding the blastocoel. The positioning of cells in the embryo at this developmental stage could be largely the result of random events, making this a stochastic model of cell lineage allocation. Contrary to such a stochastic model, some studies have detected putative differences in the lineage potential of individual blastomeres before compaction, indicating that the first cell fate decisions may occur as early as at the 4-cell stage. Using a non-invasive, quantitative in vivo imaging assay to study the kinetic behavior of Oct4, a key transcription factor (TF) controlling pre-implantation development in the mouse embryo, we identified Oct4 kinetics as a predictive measure of cell lineage patterning in the early mouse embryo. Here, we will investigate the molecular nature of this kinetic behavior that controls the development of the first specialized cells in living mouse embryos. Building upon our previous results we will test the hypothesis that TF kinetic behaviors may represent a general mechanism to establish heterogeneities and control lineage patterning in the mouse embryo by systematically measuring the kinetic parameters of the main TFs essential for pre-implantation development. We will further determine if TF kinetics are a unique mark that defines the pluripotent state by comparing TF kinetics in the embryo to embryonic stem cells.

Keywords: l301 morphology and functional imaging of cells,l309 developmental genetics - embryology in animals,l312 stem cell biology
Presynaptic and astrocytic role of Amyloid precursor protein signaling in the hippocampus (ABETAPRESYNASTRO)

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: 2014-02-01
End date: 2016-01-31
Duration (months): 24.0
Total project cost (EUR): 50000.0
EU funding (EUR): 50000.0
Participants: 1
Project status: CLOSED

Amyloid beta peptide (Abeta) is a normal product of the amyloid precursor protein (APP) proteolysis in the brain. While Abeta synaptotoxicity has been extensively studied as central to Alzheimer's disease (AD) pathogenesis, the mechanisms by which physiological Abeta regulates synapse function remain unknown. Utilizing two-photon excitation laser scanning microscopy combined with fluorescence lifetime imaging, FM-based imaging of synaptic vesicle recycling at the single-synapse level and electrophysiology, I aim to explore the molecular mechanisms modulating synaptic and astrocytic properties by physiological Abeta signaling and its effects on neuronal integration in acute hippocampus slice preparations. I will investigate the potentiation of presynaptic strength by Abeta and the transducing mechanism by answering the following questions: In the hippocampus, is the Abeta-dependent potentiation of neurotransmission synapse-specific? Can APP molecules form homodimers at presynaptic and astrocytic plasma membranes? Do local changes in the conformation of APP complexes convey intracellularly the Abeta signal? I will also investigate which effectors downstream to presynaptic APP dimers are modulated to induce Abeta-dependent potentiation of neurotransmission. I will measure the distance range at which axon-released Abeta regulates presynaptic functions during neuronal activity. With electrophysiological techniques, I will characterize the effects of Abeta on the functional input-output relationship in the hippocampal network. I will finally ask whether APP molecules also exist as dimers in astrocytes and whether APP conformation is dependent on Abeta levels and on membrane specialization in the vicinity of synaptic contacts. At the end of the project, the training in neuroimaging will offer me a great opportunity to investigate structure-functions relationship in native single synapse using cutting-edge technologies with an important impact in the field of AD.

Keywords: l502 molecular and cellular neuroscience,amyloid beta,synaptic vesicle release,astrocyte,single synapse,fluorescence lifetime imaging,electrophysiology
Irish Presidency Conference: Researcher Careers and Mobility (EIRMOB)

Framework: FP7 — Capacities
Programme: Regions of Knowledge
Destination: Regions of Knowledge
Action type: Coordination and support actions
Countries involved: Ireland
Call:  (FP7-Adhoc-2007-13, 2007)
Start date: 2013-01-01
End date: 2013-09-30
Duration (months): 9.0
Total project cost (EUR): 216243.4
EU funding (EUR): 200000.0
Participants: 1
Project status: CLOSED

The conference will focus on a key component of the European Research Area (ERA), namely, the development of an open labour market for researchers; to ensure the removal of barriers to researcher mobility, training and attractive careers. The overall impact of this conference will be to improve the coordination and coherence of policy initiatives and actions at EU and national levels and thereby will contribute to advance the realisation of the objectives of the Innovation Union initiative, including ERA. The specific focus is contributing to achieving ERA by the deadline set at 2014. The conference will succeed in these aims through the active participation of the European Commission, Member & Associated States, key international stakeholders (including the European Parliament, European Universities Association, European Science Foundation and EURODOC) and the broad research community. This conference, while stand alone in its own right, should be seen in the context of successive activities following from the Cypriot and leading into the Lithuanian Presidencies.

Keywords: careers,mobility,researchers,doctoral training,immigration,social security,pensions
Investigation of novel vertical take-off and landing (VTOL) aircraft concept, designed for operations in urban areas (ANULOID)

Framework: FP7 — Cooperation
Programme: Transport (including Aeronautics)
Destination: Aeronautics and air transport
Action type: Collaborative project
Countries involved: Italy,France,Netherlands,Czechia
Call:  (FP7-AAT-2012-RTD-L0, 2012)
Start date: 2013-04-01
End date: 2015-03-31
Duration (months): 24.0
Total project cost (EUR): 763653.1
EU funding (EUR): 577924.0
Participants: 5
Project status: CLOSED

Principal objective of proposed project is computational and experimental investigation of novel concept of VTOL aircraft with nickname „Anuloid“ regarding its flight properties and flying qualities, and compare „Anuloid“ to helicopters, tilt rotor aircraft, or other VTOL aircraft concepts, in relation to potential utilization for transport missions in urban areas.

Keywords: aircraft,vtol,urban,transport,ducted fan
Ribosome defects in cancer (RIBOCANCER)

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,Belgium
Call:  (ERC-2013-StG, 2013)
Start date: 2014-01-01
End date: 2018-12-31
Duration (months): 60.0
Total project cost (EUR): 1497038.0
EU funding (EUR): 1497038.0
Participants: 2
Project status: CLOSED

Cancer cells are defective in vital cell functions such as cell cycle control and response to growth signals. We found that cancer cells acquire defects in yet another vital function: translation of mRNA into proteins. We saw that 9.8% of children with T-cell leukemia (T-ALL) harbor acquired mutations in the ribosome, the cellular protein translation factory. We found mutations in RPL10, RPL5 and RPL22, 3 proteins of the large 60S ribosomal subunit. Strikingly, 6.5% of T-ALL patients had the same RPL10 R98S missense mutation. Although congenital ribosome defects were previously linked to higher cancer risk, the concept that defects in the ribosome are acquired during life and are selected for in cancer is novel. In addition, it is currently not understood by what mechanism ribosome defects are carcinogenic. Patients with inherited ribosome defects are predisposed to all types of cancer. Therefore, other cancers than T-ALL may show acquired defects in the ribosome and I want to explore the prevalence of acquired ribosome defects in various cancer types. Second, I want to explore by which mechanism ribosome mutations promote cancer. Initially, I will focus on the RPL10 R98S mutation, the most frequent acquired ribosome defect we found so far. We will test the effect of RPL10 R98S on cell behavior parameters such as self-renewal capacity and resistance to apoptosis. I hypothesize that altered translation of a subset of cellular mRNAs, including mRNAs coding major tumor suppressors or oncogenes, may explain the oncogenic action of RPL10 R98S. Therefore, we will identify all mRNAs with altered translation efficiency or fidelity in RPL10 R98S cells. In addition, we will test if RPL10 R98S promotes cancer by altering extra-ribosomal roles of RPL10 or by driving inactivation of the TP53 pathway. Finally, acquired ribosome defects may represent a novel target for cancer therapy and we will test if ribosome defective cancer cells are hypersensitive to translation inhibitors.
Multiple-Fibre Frequency Resolved Interferometer [MuFFIn] for spatio-temporal metrology of ultrashort laser beams (MUFFIN)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Proof of concept grants
Action type: Support for frontier research (ERC)
Countries involved: France
Call:  (ERC-2012-PoC, 2012)
Start date: 2013-04-01
End date: 2014-03-31
Duration (months): 12.0
Total project cost (EUR): 142600.0
EU funding (EUR): 142600.0
Participants: 1
Project status: CLOSED

Due to the extraordinary instantaneous power of femtosecond lasers, the list of their scientific as well as societal applications has been growing at an increasing rate since their invention in the mid-80’s. A real need of the community working with ultrashort lasers is to simultaneously characterize the laser beam structure in space and time, i.e. to measure E(r,t) for femtosecond laser beams. Indeed, the temporal structure of ultrashort laser often depends on space: such beams are said to exhibit spatio-temporal couplings (STC). STC are presently one of the main Achille’s heals of ultrashort lasers, which can considerably degrade their performances. Yet, no commercial instrument neither a research laboratory prototype is available to measure spatio-temporal couplings of ultrashort lasers. We have recently worked out and patented the principle of a measurement device that provides a simple and efficient solution to this timely problem. This method is called MuFFIn, for Multiple-Fibre Frequency-resolved Interferometer. Based on these innovation breakthroughs, our project aims at bringing spatio-temporal measurements from fundamental research to routine metrology, by providing ultrafast lasers users with a commercial, simple and easy-to-use device to fully characterize these beams. We apply to the ERC PoC grant to build a prototype of this device, evaluate the potential market for this metrology device, and perform the first steps of technological transfer to an industrial partner specialized in laser beam characterization. A memorandum of Understanding is under negotiation with a potential industrial partner, FATSLITE. This partner is ready to be involved in the definition steps of the device specifications, and then needs a real prototype to evaluate the potential of our technique.

Keywords: 240013