Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
New Therapeutics Strategies for the Treatment of Pediatric Brain Tumors (PEDIAVIR)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-04-01
End date: 2015-03-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

High-risk pediatric brain tumors constitute the leading cause of cancer death in children and despite the improvement of diagnostic and therapeutic approaches children with these malignancies have a very poor prognosis. Thus, it is clear that the management of these malignancies is suboptimal and novel targeted therapeutic strategies are required. Recently, a cancer stem cell population has been found responsible for the initiation of adult and pediatric brain tumors and may constitute the cellular basis for the resistance of these tumors to chemotherapy and radiotherapy and a more reliable model to study these malignancies. One of the approaches used to design novel, rational, and effective treatments directed against the molecular defects of these tumors involves the use of oncolytic adenoviruses. Our group previously reported the anti-glioma effect of the tumor-selective adenovirus, Delta-24-RGD engineered to selectively replicate in cells that harbor an abnormal RB pathway, a hallmark of cancer. We hypothesize that a targeted oncolytic adenovirus design to target not only the bulk of the tumor but also the BTSCs population, which account for resistance and recurrence, may constitute a significant improvement of the prognosis and quality of life of patient with pediatric brain tumors. Since the percentage of BTSCs would vary along the different pediatric brain tumors this strategy will be likely to be used in combinations, to maximize clinical impact and to minimize opportunities for resistant cancer cells to emerge. Consequently, we shall evaluate the cytotoxic effect of Delta-24-RGD in combination with temozolomide. Importantly, Delta-24-RGD in combination with chemotherapy would avoid the use of radiotherapy which, in turn, will prevent the subsequent loss of cognitive function without compromising disease control and thus, improving the overall quality of life for these children.

Keywords: oncolytic adenoviruses,pediatric brain tumors,cancer stem cells,chemotherapy
Exploring the fundamental biology of microsporidian mitosomes (MICMIT)

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-2010-IEF, 2010)
Start date: 2011-05-02
End date: 2013-05-01
Duration (months): 24.0
Total project cost (EUR): 200549.6
EU funding (EUR): 200549.6
Participants: 1
Project status: CLOSED

Microsporidia are tiny obligate intracellular parasites of other eukaryotes including patients with HIV/AIDS. Despite their importance, detailed knowledge of the biology of microsporidia is limited. Microsporidia were thought to lack mitochondria but the proposed host laboratory discovered, and have started to functionally characterise, highly reduced remnant mitochondria in these parasites, called mitosomes, which do not make ATP. Mitosomes are vital for parasite survival because they contain key components of the essential pathway for mitochondrial iron-sulphur cluster biosynthesis. However, from published and in- house genome data it appears that the transport proteins that support mitochondrial Fe-S protein biogenesis in model organisms, have been lost by the parasites. These data raise fundamental questions of how mitosomes function and import the substrates they need to produce Fe-S clusters or export the product(s) of this metabolism that (in model organisms) are needed for the biogenesis of essential cytosolic and nuclear Fe-S proteins. In the present proposal I will tackle these questions using a interdisciplinary program combining bioinformatics and organelle proteomics to identify putative mitosome proteins including transporters, molecular cell biology to functionally characterise these proteins, and detailed light and electron microscopy to confirm their localisation. The project will enhance my individual competence and potential for career development through experience of working in a leading UK laboratory with a track record of research training, international collaboration and scientific excellence.

Keywords: parasites,mitosomes,evolution,proteomics,electron microscopy,transport proteins
Mechanisms coordinating chromosome replication with transcription (REPTRA)

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: Italy
Call:  (FP7-PEOPLE-2010-IEF, 2010)
Start date: 2012-03-01
End date: 2014-02-28
Duration (months): 24.0
Total project cost (EUR): 188612.0
EU funding (EUR): 188612.0
Participants: 1
Project status: CLOSED

Genome stability during chromosome replication can be challenged by drugs affecting fork progression and intra-S DNA damage. While the mechanisms preserving the integrity of replicating chromosomes in response to replication stress induced by exogenous genotoxic events have been widely studied (Branzei and Foiani 2005; Branzei and Foiani 2007), those controlling fork stability under unperturbed conditions are less understood. Specialized networks control the collision between replication forks and transcription; preventing recombinogenic events. The host laboratory has contributed to elucidate the regulatory processes controlling the integrity of replication forks in response to genotoxic events and the architectural pathway protecting chromosome integrity by coordinating DNA replication and transcription. The overarching aim of this proposal is to understand the mechanisms coordinating replication fork progression across transcribed units using budding yeast as a model organism and a combination of mechanistic, genetic and genomic approaches. The first objective would be to identify and characterize the Mec1 and Rad53-mediated checkpoint mechanisms that control fork stability at transcribed regions while the second is to study whether the checkpoint influences the Top2-mediated epigenetic mechanism coordinating S phase transcription. The rationale of the present project is based on the observations that i) transcribed regions cause fork pausing and the collision between replication forks and transcription bubbles is highly coordinated ii) the replication checkpoint response controls the stability of paused forks iii) replication termination is influenced by transcription iv) oncogene activation leads to massive transcription deregulation and replication stress. The expected findings should have important implications for elucidating the cellular mechanisms preventing genome instability and those pathological processes causing genome rearrangements and cancer.

Keywords: yeast,dna replication,transcription,genomic instability,dna topology,replication stress,check point response,nuclear pore complex,mrna export
Ecological and life-history bases of sexual selection and sex roles in birds (SEXUAL SELECTION)

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-2010-IEF, 2010)
Start date: 2011-09-01
End date: 2013-08-31
Duration (months): 24.0
Total project cost (EUR): 273480.0
EU funding (EUR): 273480.0
Participants: 1
Project status: CLOSED

Sexual selection is widely viewed as one of the major mechanisms of evolution and impacts on a wide range of organisms’ traits from the genomic level to social behaviour. Here I propose a multidisciplinary research programme that combines the approaches and tools of evolutionary biology, brain research and advanced phylogenetic statistics to investigate three fundamental but controversial aspects of sexual selection. First, the causative relationship proposed between the intensity of sexual selection and the disparity in parental care between the sexes is ambiguous. Using a large dataset on reproductive behaviour, ecology and life history of birds and new directional comparative methods I will test whether evolutionary changes in intensity of sexual determines parental care patterns or vice versa. Furthermore, I will test new hypotheses on the relationships of sexual selection to finer components of care, and also to parental sex roles, not investigated by earlier works. Second, I will conduct new analyses on how sexual selection affects (or is affected by) brain size evolution, including tests to explore causative relationships between these traits and also between brain size and parental sex roles. Finally, I will investigate how sexual selection affects the rates of phenotypic changes, that is important for the understanding of basic evolutionary processes (e.g. speciation) but has been rarely estimated empirically by comparative studies. The proposed projects will provide an excellent opportunity to learn new research methods and to produce new and valuable scientific results in the field of evolutionary biology. The Fellowship will also strength my research management and communication skills, and increase my general knowledge on international science that is essential for my future academic career from running independent research to high quality teaching.

Keywords: sexual selection,parental care,sex roles,brain evolution,rate of evolution
The DNA damage response pathway in MYCN amplified neuroblastoma (DDR-MYCN-NB)

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-2010-IEF, 2010)
Start date: 2012-01-01
End date: 2013-12-31
Duration (months): 24.0
Total project cost (EUR): 169363.2
EU funding (EUR): 169363.2
Participants: 1
Project status: CLOSED

Accurate replication of the genome is very important in cells to prevent the propagation of mutations which cause tumour development. After DNA damage, normal non-cancerous cells arrest the cell cycle in G1 to prevent cell growth until DNA damage is repaired or, if levels of damage are high, cells undergo programmed cell death. Stress responses leading to a DNA damage response stem from different sources and activate distinct pathways. However, they converge on the same components of the cell cycle machinery in the G1 phase of the cell cycle, namely the cyclin dependent kinases. To investigate the mechanisms that MYC proteins affect the G1 checkpoint, we propose to use neuroblastoma with deregulated MYCN expression as a paradigm to examine the mechanisms that MYC proteins act on the DNA damage response pathway. This DNA damage pathway is complex and acts in two main stages, an early inhibition of cyclin dependent kinase inhibitors by redistribution of p21WAF1 and a more sustained transcriptional response is mediated by p53. To appreciate the complexity of the DNA damage response pathway experimental data will be integrated with computer based mathematical modelling techniques to build a model of this pathway and how it is affected by deregulated MYCN expression. Understanding the effect of MYC proteins on the DNA damage pathway is essential for future advances in cancer treatments, as a large number of current chemotherapeutics are DNA damaging agents. This project will provide a general model for all cancer types driven by MYC proteins, it will also provide important prognostic indicators and new drug targets for the treatment of neuroblastoma- a cancer that accounts for 8% of all childhood malignancies where patients diagnosed with high risk neuroblastoma have a 5-year overall survival of only ~60%.

Keywords: dna damage,myc,neuroblastoma,systems biology,translational,p21,cyclin dependent kinase,cell cycle,g1 arrest
Three-dimensional multiscale model for material degradation and fracture in polycrystalline materials. (3D MULTISCALE MODEL)

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-2010-IEF, 2010)
Start date: 2011-07-15
End date: 2013-07-14
Duration (months): 24.0
Total project cost (EUR): 210092.8
EU funding (EUR): 210092.8
Participants: 1
Project status: CLOSED

The aim of this proposal is the formulation and implementation of a three-dimensional multiscale model for material degradation and fracture in polycrystalline materials. The initiation and propagation of cracks is an inherently multiscale phenomenon, in which the micro-scale material features have a direct influence on the macro-continuum response and this in turn affects the micro-state evolution. Single scale analyses are not able to address specific crack problems, due to the inability of capturing essential geometric effects related to different grain morphology, size, orientation and mechanical behavior. Multiscale methods appear to be an effective tool on investigation, as they provide and link information at different scales. The proposed model will be based on a new cohesive grain boundary integral formulation. The outcome of the project will be an high-performance computer code for 3D multiscale analysis of material degradation and damage initiation and propagation in polycrystalline materials. This could be commercialized in the future and find application in the Aerospace and Automotive industries, helping EU gain a competitive edge in this field. The stand-alone microstructure model could find application in the design of micro-devices for bioengineering applications. There are several reasons for the timing of the project: multiscale modelling is an area of recognized importance, the present work goes beyond the state of the art and it will help Europe maintain scientific competitiveness. Moreover, the outcome of the project will help EU industries in the future. Several FP7 projects contribute to this theme and the project will complement those works. Finally, the project will noticeably expand the scientific and complementary skills of the fellow, contributing to the attainment of a position of professional maturity. It will link the fellow to a strong institution assisting in the construction of the European Research Area.

Keywords: mechanical engineering,materials engineering,aircraft materials,simulation engineering
Blending biophysical and drug discovery platforms to investigate allosterism in G-protein-coupled receptors (GPCRs) and find novel allosteric modulators for neurotherapeutics development (FATOKUNEUFP7IIF2010)

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-2010-IIF, 2010)
Start date: 2011-08-01
End date: 2013-07-31
Duration (months): 24.0
Total project cost (EUR): 210092.8
EU funding (EUR): 210092.8
Participants: 1
Project status: CLOSED

The global socio-economic and health burden of neurological and neurodegenerative diseases is enormous, impacting overall quality of life and overwhelming available resources. The situation is worrying, considering the predicted future explosion in the aging population. There are currently no ideal drugs to manage these debilitating conditions. This project will thus achieve two major aims: 1. Use biophysical approaches to improve fidelity of pharmacological observations of ligand-receptor interactions for determining mechanisms of action. This will allow investigations of such interactions at the single-cell level, as opposed to current investigations in cell populations, which are less accurate. 2. Use the platform in aim 1 to develop screening assays to identify allosteric modulators of three receptors of exceptional clinical significance: adenosine, metabotropic and GABAB receptors. Allosteric modulators bind to a site on the receptor different from where the endogenous ligand binds, with better selectivity and reduced incidence of side effects compared to orthosteric modulators that bind to the same place as the endogenous ligand. The inter- and multi-disciplinary project combines pharmacology, biochemistry, molecular and cell biology, medicinal and synthetic chemistry, drug discovery and biophysics. It is intersectoral, featuring collaboration with a spin-out company (CellAura). Allosteric modulators would be developed as pharmacological tools or novel drugs in an arrangement that creates opportunities for longer-term collaboration with the USA, especially Johns Hopkins University. The Fellow will bring unique expertise in drug discovery and neuroscience. He will enhance his career prospect by engaging in a novel project different in focus and approach from what he undertook previously. The project will attain ERA objectives: product and technology development, patent ownership, product commercialization and creation of spin-outs and job opportunities.

Keywords: pharmacological sciences,drug discovery,pharmacy,toxicology,health sciences,neurology,neurochemistry,brain research,degenerative diseases,neurophysiology,molecular biology,biophysics,receptor
Constructing Solidarities. Kinship Ties and Social Networks in the Urban Communities of Italy and the Low Countries, 1250-1550 (MCEUICS)

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: Italy
Call:  (FP7-PEOPLE-2010-IEF, 2010)
Start date: 2011-09-01
End date: 2012-08-31
Duration (months): 12.0
Total project cost (EUR): 91706.0
EU funding (EUR): 91706.0
Participants: 1
Project status: CLOSED

In the rapidly growing cities of late medieval and early modern Italy and the Low Countries new forms of trust emerged that gave social cohesion to the urban community. The new trust networks, based on the building blocks of kinship ties and extra-familial co-operation, strengthened the processes of social integration and community building in the medieval city. This project aims to reveal the social mechanisms that underlay these solidarities as well as to determine the factors that facilitated their formation. It does so by comparing the developments in cities with different political and socio-economic profiles from Italy and the Low Countries. This comparative research will enhance our knowledge about the structural factors that explain the relation between the emergence of trust networks – in particular the ruling elites and the guild organisations – and the evolution of urban communities and civil society. This approach raises methodological challenges concerning the comparison of different case studies and diverse data, which must be dealt with. The research will also contribute to the interdisciplinary debate about the practice of trust and the functioning of familial and extra-familial solidarity, drawing on sociological theory pertaining to trust and social networks. Finally, the research will add to our understanding of the bottom-up trust-building strategies of actors of various political and socio-economic backgrounds, thereby assessing the impact of more general forms of trust embodied by the medieval urban corporate and public institutions. The central question, however, is to explain how kinship ties and extra-familial social networks strengthened and facilitated the process of urban community building in Western Europe from 1250 to 1550.

Keywords: humanities,urban history,italy,low countries,cities and towns,trust,social history,social networks,family structure,communities,institutions,social theory,corporatism,medieval and early modern history
Bilingualism Impact on Reading Development (BIRD)

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: Spain
Call:  (FP7-PEOPLE-2010-IEF, 2010)
Start date: 2011-07-01
End date: 2013-06-30
Duration (months): 24.0
Total project cost (EUR): 159365.6
EU funding (EUR): 159365.6
Participants: 1
Project status: CLOSED

With the European Union, a growing group of children learns how to read in two languages at the same time. Interestingly, the Basque language is used in Spanish and French regions of Europe and many children must learn to read in Basque in parallel to either an opaque (French) or a shallow (Spanish) orthography. This project investigates the foundations of bilingual reading acquisition, taking into account the features of the languages learned. It has been shown that the chunk size of letter strings processing depends on grapheme-to-phoneme conversion rules’ regularity, defining the extent to which decoding and lexical reading strategies are taxed. Few studies have focused on bilingualism impact on reading strategies and disorders. Yet, reading difficulties occur also in bilinguals and adapted diagnostic and remediation tools for this population are needed. Performance of Basque-Spanish and Basque-French bilinguals attending Basque-medium schools in Grade 2 and Grade 5 will be assessed on Basque reading, related cognitive skills and their electrophysiological markers. Taking into account the transparency of the second language learned, the present study aims at identifying differences in developmental time course of reading acquisition and in manifestations of reading disorders in Basque. Because the tests given will be identical for the two bilingual groups, i.e., in Basque, data will bring evidence missing in previous cross-linguistic studies to identify cognitive predictors and cerebral markers of normal and impaired reading acquisition in regular and irregular orthographies. Such cross-sectional study will enable to determine to what extent linguistic features positively or negatively impact on reading development. Importantly, the study will have concrete outcomes such as normative data to assess literacy in Basque, offering the opportunity to design adapted diagnostic and remediation tools for Basque literacy disorders in French and Spanish regions of Europe.

Keywords: bilingualism,basque language,reading development,reading disorders,reading procedures,orthographic transparency,phonology,orthography,visual attention,education