Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
An Account of Legal Obligation (LEGO)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Germany
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2015-02-01
End date: 2017-01-31
Duration (months): 24.0
Total project cost (EUR): 223778.4
EU funding (EUR): 223778.4
Participants: 1
Project status: CLOSED

This research project addresses an important legal issue, that of legal obligation. The notion of legal obligation features centrally in legal practices and studies, since law and obligation are widely regarded as closely connected by virtue of the authoritative structure of law. Now, any explanation of legal obligation aspiring to some degree of comprehensiveness must explain both the nature of the obligatory force of law and its foundation. That is, an account of legal obligation has to elucidate both what enables the law to hold us bound to do anything and why legal requirements should be taken to be binding. In working toward an explanation of legal obligation, thus, we must operate on two levels, identifying on the one hand a concept of legal obligation, and on the other the basis of the obligatory force of law. This two-pronged exploration sets up a number of questions for us to address: in conjunction with the definitional question “What is legal obligation?”—or “What do we mean by obligation and how does it apply to legal contexts?”—we must also ask “Why ought one to do what the law requires?” and “Whence does the obligatory force of legal requirements come?” or, stated otherwise, “What makes the law binding?” These are the questions around which the project is framed: they are tackled by working together into a coherent whole a theoretical investigation and a practical one. Each feeds into the other, since the very concept of legal obligation is clarified by showing how obligation makes its way into the practices out of which law is made, a process through which we can show what the obligation-imposing capacity of law rests on and where it comes from. In this way we can arrive at a comprehensive conception of legal obligation—the ultimate aim of this project—that attacks the problem in a systematic fashion.

Keywords: obligation,legal duty,concept of law,legal system,philosophy of law,normativity,ought,practical philosophy,kant,moral theory
Identification of drug-resistance genes for the development of effective combined therapies for melanoma (MELANOMA DRUG RESIST)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2014-07-01
End date: 2016-06-30
Duration (months): 24.0
Total project cost (EUR): 221606.4
EU funding (EUR): 221606.4
Participants: 1
Project status: CLOSED

Malignant melanoma is a highly aggressive form of skin cancer with a poor outcome following metastatic spread. Chemotherapies for metastatic melanoma are rarely curative because of the emergence of clones from within the tumor that carry lesions in genes that confer therapeutic resistance. Understanding the genetic culprits of drug resistance will allow the rationale development of combination therapies that may circumvent the occurrence of resistance. Here I propose to combine different cutting-edge technologies and functional screenings in human early-passage melanoma cell cultures (EMCCs) to identify clinically relevant melanoma drug-resistance genes and consequently to develop new effective combination therapies by a data-driven approach. I will screen a library of drugs across a collection of EMCCs and in concert analyze the genome of each EMCC for mutations, epimutations and chromosomal aberrations. EMCCs found to be intrinsically resistant to a given drug will be screened with a short-hairpin-RNA library to identify genes whose knockdown reverts resistance. Those EMCCs sensitive to a given drug will be infected with lentiviral-vector based insertional mutagens to screen for genes whose upregulation mediates drug resistance, thus identifying mechanisms that may be associated with relapse in patients treated with these compounds. These 2 approaches will provide a collection of drug-resistance and -sensitivity genes that will be then validated in vitro, in vivo and in clinical samples. The knowledge of drug-resistance genes and genomic lesions carried by each EMCC will guide the design of new therapies based on the combination of multiple compounds targeting both the mutated gene and the EMCC-specific drug-resistance gene. The new combination regimens will be tested in vitro on EMCCs and in vivo in xenotransplant models. These results will pave the way to preclinical and clinical development of new combined therapies for the efficient eradication of melanoma.

Keywords: melanoma,drug resistance,overcoming drug resistance,combined therapies,drug-resistance genes,targeted therapies,functional screening,drug sensitivity,genome sequencing,insertional mutagenesis
Coevolution of the Cladoniaceae and associated fungi (CLADOF)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Finland
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2014-07-01
End date: 2016-06-30
Duration (months): 24.0
Total project cost (EUR): 199016.4
EU funding (EUR): 199016.4
Participants: 1
Project status: CLOSED

Cladoniaceae is one of the largest and most diverse families of lichens. It includes about 500 species. The species comprise significant components of numerous terrestrial ecosystems around the world. In addition, Cladoniaceae has proved to be an exceptionally favored host for numerous, poorly known lichenicolous fungi. Altogether 83 species of these fungi have been reported to grow on the Cladoniaceae and most are specified to live on single host taxon only. Our goal is to combine the phylogeny of the Cladoniaceae with complete chemical and distributional data, screen the associated fungi, and produce the first inclusive phylogeny of the latter. This data will be used in studying coevolution of the partners, specificity, evolution of different life strategies as well as evolutionary timing and biogeographical origin of the diversifications and associations. We will also screen for the suitable DNA barcodes for the species. Hypotheses: We anticipate multiple origins of lichenicolous fungi, partial parallel cladogenesis, and Gondwanan origin for the Cladoniaceae, but current patterns of distribution are probably partly explained by recent dispersal. We also anticipate high host specificity and a correlation between chemical composition of the hosts and associated fungi, and that lichenicolous habit is mostly derived from lichen habit, but that lichenicolous habit has also been commonly lost (instability). Further, we anticipate that the host/parasite association is of ancient origin. The results will provide data for applied research, nature conservation, species monitoring, and screening of biodiversity.

Keywords: ascomycota,coevolution,evolutionary timing,lichen forming fungi,lichenicolous fungi,molecular phylogeny
Elucidating the role of microbial communities in cod larval death and survival (COD LARVAL SURVIVAL)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Norway
Call:  (FP7-PEOPLE-2013-IIF, 2013)
Start date: 2014-04-01
End date: 2017-01-31
Duration (months): 24.0
Total project cost (EUR): 322614.8
EU funding (EUR): 322614.8
Participants: 1
Project status: CLOSED

This proposal contributes to solve a significant problem in commercial aquaculture: namely the high mortality of fish larvae caused by microbial infection. To enhance the survival of cod larvae I will gain in-depth insight into the microbiome of the cod larvae gastrointestinal tract by using novel and advanced correlative three-dimensional cryogenic-transmission electron microscopy and fluorescence in situ hybridization, and large-volume high-resolution focused ion beam scanning electron microscopy imaging approaches that were developed at the University of California, Berkeley and the Lawrence Berkeley National Laboratory in the U.S. I will adapt and apply these state-of-the-art imaging techniques to a research effort at the Norwegian University of Science and Technology (NTNU) designed to replace trial-and-error management of bacteria in larval cod production with an evidence-based gnotobiotic system that has been developed at NTNU. This system reduces the inherent complexity of microbial control in the wild with a carefully designed protocol beginning with bacteria-free cod larvae, and introducing bacteria stepwise as the larvae develop. Specifically I will address the following three questions: (1) Do different microbial conditions have an effect on the survival, growth and development of the fish larvae? (2) Do probionts and pathogens colonize the same region of the gastrointestinal tract? (3) What happens to the indigenous intestinal microbiota and the host during infection? By adapting these novel technologies in the context of commercial/industrial aquaculture I will not only create long-term collaborations and mutual co-operation between Europe and the U.S., but also significantly contribute to the wellbeing of the commercial aquaculture industry, which is of significant importance to both the Norwegian as well as the European economy. Thus, my proposed efforts will contribute to both European scientific excellence and European commercial competitiveness.

Keywords: atlantic cod larvae,correlative microscopy,cryogenic-tem,fib-sem,electron microscopy,gnotobiotic system,bacteria,probiotic,pathogen,gut colonization,host-microbe interactions
POTENTIAL OF INDUCED PLURIPOTENT STEM CELLS FOR THE TREATMENT OF CRIGLER-NAJJAR LIVER DISEASE: A PRECLINICAL SAFETY ASSESSMENT (CN-I LIVER THERAPY)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Switzerland
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2014-11-01
End date: 2016-10-31
Duration (months): 24.0
Total project cost (EUR): 199317.6
EU funding (EUR): 199317.6
Participants: 1
Project status: CLOSED

Currently, the only cure for many inherited metabolic liver diseases with severe extra-hepatic manifestations, such as Crigler-Najjar disease (CNI), is liver transplantation (LT). LT goes together with heavy surgery, life-long immunosuppression and important public health costs. Development of less invasive treatments will permit important benefits for the patients and economic savings. Combination of gene therapy and hepatocyte (HEP) transplantation is a promising alternative to LT, correcting the metabolic defect while keeping in place the normal native liver. Nevertheless, the major obstacle has been shown to be the insufficient amount of corrected HEP available for transplantation. Induced pluripotent stem cells (iPS) are endowed with intrinsic self-renewal ability and the potential to differentiate into any of the three germ layers allowing cell amplification before differentiation. As such, iPS are heralded as the most promising avenue for cell-based therapeutics. However, recent evidences indicate that the epigenetic features of iPS are heterogeneous and notably influenced by the tissue of origin of the reprogrammed cells. Hypothesis: HEP reprogramming and differentiation induce profound epigenetic changes that could affect the safety of gene and stem cell therapy combination approach. Objectives: 1) Reprogramming of patient-specific CNI-HEP into iPS. 2) Correction of CNI-iPS by ex vivo lentiviral transduction. 3) Large-scale amplification of the corrected CNI-iPS and differentiation to HEP-like cells. 4) Epigenetic analysis of patient CNI-HEP, CN-iPS and the differentiated-corrected cells. 5) Therapeutic assessment of corrected CN-HEP-like cells into the liver of the CNI animal model. This project will allow a step forward to studying the safety, efficacy and clinical potential of differentiated cells derived from patient-specific iPS. Importantly, not only CNI disease but also many other inborn liver disorders are potentially treatable via this approach.

Keywords: inherited metabolic liver diseases,crigler-najjar,ex-vivo gene therapy,induced pluripotent stem cells,epigenetic reprogramming
Exploring Anti-GentrificAtion PracticEs and policies in Southern European Cities (AGAPE)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2014-10-01
End date: 2016-09-30
Duration (months): 24.0
Total project cost (EUR): 221606.4
EU funding (EUR): 221606.4
Participants: 1
Project status: CLOSED

The overall aim of AGAPE is to explore and improve our knowledge of anti-gentrification practices as performed in the urban space of Southern European cities (SECs), specifically Rome, Madrid and Athens, with a particular focus on their incorporation into - and capabilities to inform - local policy makings. In SECs the effects of gentrification are now being exacerbated by the debt crisis and the consequential austerity behaviors of nation states. For this reason, SECs offer an opportune setting in which to study the relationship between gentrification and policy, as well as forms of resistance and alternative responses to gentrification. Empirical evidence suggests that there are emerging practices of reaction, and alternative solutions, to the hegemonic narrative of the “commodified city” in SECs that are directly addressing the broader issue of the habitability of the city. However, these practices appear to be fragmented and we lack systematic understanding of their potential and their capabilities in countering urban inequalities. As such anti-gentrification practices and policies performed in these three SECs will be investigated and compared in order to construct a model of territorial capacities: capacities to counter the hegemony of gentrification at this particular ‘political’ moment in time, by incorporating far sighted and socially just policies for the re-use of the material assets of these cities. Such an exploration will provide much needed theoretical and empirical material for a post-crisis urban agenda aimed at achieving social justice and equity. The findings of the research will inform an academic narrative of resistance that will highlight ‘alternative narratives’ based on counter-gentrification practices in these three cities. The research findings will be also rendered in forms of an anti-gentrification toolkit that will provide the basic tools that local communities can draw on to fight gentrification and concrete ideas for policy makers.

Keywords: gentrification,anti-gentrification practicies,southern europe,alternative urban narratives,urban studies
Gold-catalysed dehydrogenative cross-coupling of arenes (AU-DOUBLEC-H)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2014-04-01
End date: 2016-03-31
Duration (months): 24.0
Total project cost (EUR): 221606.4
EU funding (EUR): 221606.4
Participants: 2
Project status: CLOSED

The usually inert carbon-hydrogen (C-H) bond is present in nearly all synthetic and naturally occurring organic molecules. The modification of organic compounds through the direct functionalisation of C-H bonds is however a highly challenging process due to their poor reactivity and the difficulty of discriminating between the many C-H bonds present in most molecules. Nevertheless, catalytic C-H activation has emerged as an increasingly promising strategy for simple and atom-economical cross-coupling of organic compounds. Compared to current methodologies that require the use of pre-functionalized starting materials, the development of general and efficient catalytic C-H activation systems could significantly reduce the amount of waste generated in synthetic reactions by (1) using readily available starting materials (2) shortening reaction sequences and (3) avoiding the stoichiometric generation of metal salts default to synthesis that rely on the use of pre-functionalised building blocks. This project aims at the development of catalytic systems for the formation of biaryls by the direct coupling of two arenes via double C-H activation. Such arylations require the selective breaking of two distinct C-H bonds followed by the subsequent C-C bond formaton. We will make use of the unique ability of gold complexes to discriminate between C-H bonds in different electronic environments depending on the oxidation state of the gold catalyst. Thus, we will develop catalytic cross-coupling processes proceeding via (1) gold(I) mediated C-H activation of electron poor arenes, (2) oxidation of the catalyst to gold(III) followed by gold(III) mediated C-H activation of electron rich arenes, and (3) C-C bond formation furnishing biaryl compounds. The described proposal will significantly contribute to the current state of the art cross-coupling methodologies and offer a direct and green approach to the synthesis of biaryl motifs.

Keywords: organic synthesis,organometallic catalysis,gold,c-h activation,cross-coupling,biaryl synthesis,green chemistry
Molecular Mechanisms of Memory Persistence (MEMORY PERSISTENCE)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2013-IIF, 2013)
Start date: 2014-05-01
End date: 2016-04-30
Duration (months): 24.0
Total project cost (EUR): 299558.4
EU funding (EUR): 299558.4
Participants: 1
Project status: CLOSED

The identification of the molecular and cellular mechanisms that lead to changes in synaptic strength has been a major focus in memory research over the last decades. These mechanisms have been posited to mediate learning and memory. Although many signaling pathways have been shown to initiate the formation of long-term memory they do not appear to be important once memory has been stored/consolidated. A general assumption in the field has been that memory does not require an active biochemical process to be sustained. This view has been challenged in the last few years by the discovery that the persistent activity of a constitutively active protein kinase, PKMζ, is required for memories to persist. This finding had a profound implication because it indicates that memory persistence requires continuous maintenance. We have found that GluA2-containing AMPA receptors (AMPARs) are critical for the expression and maintenance of long-term memories and that the persistent action of PKMζ keeps these receptors at the postsynaptic density. In this research proposal we will build on this finding to identify the components of the signaling pathways regulating the stabilization and removal of synaptic GluR2-AMPARs, and thus memory persistence. We will focus on the major pathways that regulate the trafficking of AMPARs during synaptic plasticity. We will molecularly manipulate in the expression of proteins that have recently emerged as key regulators of AMPAR trafficking and synaptic GluA2 content during synaptic plasticity. We will also study the effect that blocking the interaction of GluA2 with intracellular trafficking proteins exerts on memory persistence and on the susceptibility of memories to be erased. Finally, we will attempt to determine how GluA2 stability is linked to memory maintenance. The knowledge gained from this project may provide new insights for the development of new therapeutic strategies for memory disorders.

Keywords: learning and memory,memory maintenance,ampa receptor trafficking,glua2,signaling pathways,hippocampus,behaviour.
Dynamic spatial organization of plasma membrane proteins at the nanoscale (PM-NANOMAPS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Germany
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2014-09-01
End date: 2016-08-31
Duration (months): 24.0
Total project cost (EUR): 161968.8
EU funding (EUR): 161968.8
Participants: 1
Project status: CLOSED

Besides its function as a passive cell wall plasma membrane (PM), involved in signal transduction and cell adhesion, is essential to enable the formation of tissues. Understanding PM function requires molecular insights into its dynamic spatial organization. Recent studies show that membrane proteins rearrange laterally forming nanoclusters of various size. On the other hand, a hierarchical model of two dimensional PM organization has been proposed including transient confinement in membrane-actin-skeleton induced compartments and lipid rafts. However, an overall picture of the dynamic spatial organization of the PM requires the inclusion of protein trafficking since membrane proteins undergo a constitutive turnover transported in vesicles as cargo from and to the cytosol. The hypothesis of this project is that vesicle trafficking to and from the PM is responsible for the observation of nanoclusters in the PM. Due to the diffraction barrier it is impossible to image nanoclusters with conventional fluorescence microscopy. To avoid this limitation, I will use super-resolution fluorescence imaging methods such as direct Stochastic Optical Reconstruction Microscopy (dSTORM) and Photoactivated Localization Microscopy (PALM) combined with novel statistical cluster analysis to study quantitatively the dynamic reorganization of PM induced by protein trafficking, as well as the role played by actin-skeleton-induced compartments and lipid rafts during this process. I will apply this approach to study a wide family of membrane proteins involved in signal transduction and cell adhesion essential for embryogenesis, neurogenesis, and immune response. The outcome of the project is expected to provide fundamental new insights into PM architecture and organization including protein turnover. Since membrane proteins are one of the most attractive drug targets because they control the communication of cells with their environment, the results will be of high medical significance.

Keywords: super-resolution fluorescence microscopy,localization microscopy,plasma membrane organization,protein clusters,protein trafficking,lipid rafts