Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Cell autonomous role of beta3 integrin: function in macrophages. (MACROPHAGE ITGB3)

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: Luxembourg
Call:  (FP7-PEOPLE-2011-CIG, 2011)
Start date: 2013-09-01
End date: 2017-08-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Integrins play a key role in the binding of cells to the extra-cellular matrix, cell migration, cell-cell adhesion and cell-cell signaling. The ß3-integrin subunit is expressed in a wide range of tissues. β3 integrins occur i.e. as αvβ3 in various cell types but as αIIβ3 exclusively in megakaryo/-thrombocytes. Mice with a germline β3 integrin deficiency (β3-/-) show enhanced tumor growth and neoangiogenesis due to angiogenic signaling in endothelial cells, and are prone to systemic inflammation and atherosclerosis on high fat diet despite a severe bleeding predisposition. Based on the complex results from germline gene targeting and antibody based loss of function experiments, a cell-autonomous role of the β3 integrin is very likely. I have demonstrated that bone marrow derived β3 integrin is strongly implicated in diet induced pneumonitis, atherosclerosis and death in hyperlipidemic β3 integrin-deficient mice vivo supporting the hypothesis that β3 integrin-dependent signaling in macrophages may be anti-inflammatory. In this proposal, I would like to study the cell-specific role of β3 integrin in macrophage populations. The susceptibility to high-fat diet induced inflammation will be investigated employing newly generated mice that allow the tissue-specific deletion of the β3 integrin combined with the possibility of following the beta3 integrin expression in macrophages in vivo on the basis of a fluorescent marker. We will utilize high-throughput technologies to identify and reconstruct molecular pathways associated with β3 integrin deficiency in macrophages with regards to inflammation and atherogenesis. We will also test whether the rescue of macrophage specific expression of β3 integrin is sufficient to correct the β3 integrin deficient phenotype. Knowledge about the cell-specific function of β3 integrin is important for clinical use of non-selective β3 integrin antagonists and may illuminate novel molecular pathways in (vascular) inflammation and cancer.

Keywords: laboratory animal science,computational biology,chronic diseases,endocrinology,cardiology,degenerative diseases,nutrition related disorders,molecular genetics,functional biology,clinical bio
Computer methods to predict three-dimensional hydraulic fracture networks (COMPHYDRAULFRAC)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Life-long training and career development
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2011-CIG, 2011)
Start date: 2012-06-01
End date: 2016-05-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

The world's ever-growing rate of energy consumption urges the improvement of techniques of both fossil fuels and renewable energy. Hydraulic fracturing is a technique applied to both categories of energy sources. It consists in pumping water at a very high pressure through pre-drilled wells into the ground and generating fractures in the rock. It can be employed to extract crude oil or natural gas from the rock; it can also facilitate the extraction of heat from the earth by forming a network of underground fractures. Its application requires the design of the fracturing strategy, including the quantity and pressure of the water to be injected. Hydraulic fracturing is expensive to study both on site and in a laboratory and only limited information can be obtained wherefrom. On the contrary, computer simulations are cost-effective and time-efficient in predicting the geometry of the fractures and thus can contribute to speeding the designing process. Nevertheless, most state-of-the-art simulation methods for the fracturing process apply only to a (layerwise) homogeneous rock medium. In this project, I plan to develop efficient simulation methods with the objective of accurately predicting the three-dimensional network of hydraulic fractures, taking into account rock self-contact, inhomogeneity, and poroelasticity. I also plan to build methodologies to incorporate stratigraphic data obtained from field technologies. A technical contribution to the field of numerical analysis will be the use of variational inequalities to incorporate the inequality constraints arising in the formulation of the coupled problem between the fluid and the rock medium. I completed my doctoral study and postdoctoral training at Stanford University, United States. In April 2011, I started a four-year tenure-track Assistant Professor position in the Universitat Politecnica de Catalunya, Spain. This grant would provide me a unique opportunity to establish my research career in Europe.

Keywords: hydraulic fracturing,oil and natural gas extraction,geothermal energy,enhanced geothermal system,lubrication equation,finite element method,boundary element method,variational inequality
Apolipoprotein E gene in the Metabolic Syndrome (APOMET)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Life-long training and career development
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2011-CIG, 2011)
Start date: 2012-05-01
End date: 2016-04-30
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Metabolic Syndrome (MetS) is closely linked to disturbances in lipid and glucose metabolism and increases the risk of developing cardiovascular disease and diabetes. One-fourth of the adult European population has the MetS and a further increase is anticipated because a greater prevalence of obesity in the future. Apolipoprotein E (APOE) associates with lipoproteins and mediates theirmetabolism. In humans, the APOE gene is polymorphic and has three alleles, APOE*2, APOE*3 and APOE*4. Carrying the APOE*4 allele has been associated with an increased cardiovascular risk, predisposition to develop Alzheimer’s disease and insulin resistance. Recently, APOE*4 has also been linked with MetS. However, the mechanisms whereby this association occurs are not clear. The objective of this project is to investigate the role of APOE in metabolic syndrome. We hypothesize that APOE*4 presence determines a less flexible metabolism; i.e. an inability to effectively switch between lipids and carbohydrates for fuel and the subsequent carbohydrate intolerance. For our Work Package 1 we will employ mice whose endogenous Apoe gene has been replaced by the human APOE*3 or APOE*4 allele. We will investigate the energy substrate handling of these “humanized” mice at the whole body level by using metabolite tracers and diverse “-omics”, which will reveal why the energy generating pathways differ with apoE-isoform presence. At the population level, Work Package 2 will identify human APOE*4 carriers and investigate new APOE genetic variants to determine whether the association between APOE-isoform and metabolic syndrome is diet-dependent in the participants of the Aragon Workers Health Study, an ongoing longitudinal study targeted to study the appearance and progression of cardiovascular risk factors. By translating basic science into human studies, this project will provide new targets to prevent or treat the onset of MetS and its associated morbimortality in European populations

Keywords: apolipoproteine,apoe,apoe4,metabolic syndrome,diabetes,obesity,insulin resistance,metabolism adipose tissue,fat
MOLECULAR REGULATION OF OSTEOBLAST MOTILITY AND THE BONE-VASCULAR NICHE (CROSS-TALK IN BONE)

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-2011-CIG, 2011)
Start date: 2012-03-01
End date: 2016-02-29
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Bone is a dynamic tissue that is constantly remodelled by the coupled activities of matrix-producing osteoblasts (OBs) and matrix-resorbing osteoclasts (OCs). Uncoupled bone remodelling may lead to low bone mass, causing osteoporosis and ultimately fractures, which constitute an increasing medical- and socio-economic problem. During fracture repair, a functional relationship exists between migrating OBs and the invading vasculature. To better understand physiological and disturbed bone remodelling, bone repair, and the communication between bone and vessels, it is crucially important to investigate molecular mechanisms regulating OB function, OB motility, and the bone-vascular niche. Resulting insights can then be used to improve the current cure of osteoporosis and fracture repair. Preliminary data revealed that the homeodomain protein Tg-interacting factor (Tgif) is an important regulator of OB function. Tgif-deletion in mice causes a low bone mass with spontaneous fractures, a disturbed bone marrow vascular network, and a compromised fracture healing with a reduced OB migration. Furthermore, Tgif-deficiency reduces the expression of the angiogenic factor Vegf-A by OBs and Tgif physically interacts with the cell motility regulator focal adhesion kinase (FAK), suggesting molecular mechanisms for the role of Tgif in vivo. Thus, the objectives of this proposal are to analyze the function of Tgif (i) in OB motility and FAK signalling, and (ii) in the regulation of Vegf-A expression and the bone-vascular niche. Both objectives will be accomplished using a state-of-the-art genetic approach in mice for the targeted deletion of Tgif in OBs and a complete set of complementary in vitro assays. Taken together, this project will establish Tgif as a novel physiological regulator of OB motility and the bone-vascular niche, thus reporting clinically important knowledge to improve the treatment of low bone mass diseases and fractures.

Keywords: health sciences,orthopaedics,bone,osteoblast,cell migration,bone-vascular niche,bone repair,cellular interaction,nuclear factors
Neighbourhood choice, neighbourhood sorting, and neighbourhood effects (NBHCHOICE)

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-2011-CIG, 2011)
Start date: 2012-09-01
End date: 2016-11-30
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

There is a strong belief among academics and policy makers that living in deprived neighbourhoods has a negative effect on residents’ life chances over and above the effect of their individual characteristics: so-called neighbourhood effects. The concept of neighbourhood effects – as an independent residential and social environment effect on individual outcomes – is academically intriguing, but has also been embraced by policy makers, mainly in connection with unemployment and a lack of social mobility. The neighbourhood effects discourse has had a major impact on urban and neighbourhood policies and has influenced governments to spend large sums of money on area based policies. A small but growing critical literature, questions the evidence base of neighbourhood effects. Although it is likely that neighbourhood effects exist, we do not know enough about the causal mechanisms which produce them, their relative importance compared to individual characteristics such as education, and under which circumstances and where these effects are important. This interdisciplinary and international proposal argues that in order to further our understanding of neighbourhood effects, and to provide a solid and sophisticated evidence base for policies aimed at deconcentrating poverty, we should investigate the effects of selection mechanisms into and out of neighbourhoods. NBHCHOICE has three objectives 1) to further develop the theoretical framework linking neighbourhood choice and neighbourhood effects 2) to empirically investigate neighbourhood choice over the life course, and 3) to integrate models of neighbourhood choice with models of neighbourhood effects. The project will use large longitudinal datasets from The Netherlands, UK and Sweden and will bring together researchers from various countries. NBHCHOICE will contribute to the development of theory, to more targeted and effective policy measures, to the career development of the applicant, and to the host institute.

Keywords: social sciences,economic geography,human geography,demography,urban sociology
Guidance Mechanisms of Cell Migration (GMCM)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Life-long training and career development
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2011-CIG, 2011)
Start date: 2012-09-01
End date: 2016-08-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Directed cell migration is a crucial process in all organisms from embryonic development through adulthood. It is essential in embryonic development for proper formation of tissues and organs and in adult stages for tissue angiogenesis and wound healing. However, it is also a major contributor to diseases such as in cancer and chronic inflammation. The basic features of how a cell moves have been well characterized in tissue culture systems; however, how cells interact with the environment in vivo and how these complex interactions shape their behavior are less well understood. A central feature of directed cell migration is the perception of attractant and repellant cues. Cells respond to signals as they migrate toward and associate with target sites. The importance of signals and behaviors of the tissue microenvironment for this migratory response remain largely unexplored in vivo. We will use germ cells in the Drosophila embryo as a model system in which to explore these important questions. It is now well established that some extracellular signals, such as Wnt and Hh, are lipid-modified and that this modification is functionally required. My work has demonstrated a novel function in multicellular organisms of a highly conserved pathway that produces and exports prenylated signals. The use of this unconventional, signal-peptide independent, secretory pathway for chemoattractant export had previously only been demonstrated for the prenylated a-factor pheromone in S. Cerevisiae. However, all members of this pathway are conserved from yeast to humans, leading to the intriguing possibility that chemoattractants are similarly produced and exported in multicellular eukaryotes. My goal is to identify the prenylated chemoattractant and elucidate the molecular and cellular role of this pathway in migrating germ cells and soma-germline communication.This will shed light on the roles of this pathway in higher eukaryotes.

Keywords: cell migration,drosophila,germ cells,prenylation,abc transporter,attractive signal,target tissue,microenvironment
The impact of the tissue microenvironment on the microRNAs in chronic lymphocytic leukemia (VIMIRNASCLL)

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: Italy
Call:  (FP7-PEOPLE-2011-CIG, 2011)
Start date: 2012-04-01
End date: 2016-03-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Despite the advancement achieved in the treatment of Chronic Lymphocytic Leukemia (CLL), it remains an incurable disease. The current approach to handle CLL patients is “watch and wait” and the treatment starts when the disease is progressing. Therefore, one of the major challenges is to find genes responsible for the progression of the disease and discover the mechanisms that influence the expression of these genes. All relevant events of CLL occur in tissues where leukemic cells can be exposed to (auto) Ag stimulation and/or utilize microenvironment interaction to avoid apoptosis and acquire better growing conditions. We have recently identified several microRNAs deregulated over the progression of the disease. Here we propose to investigate the influence that components of the microenvironment could have on the expression of microRNAs deregulated in CLL cells over the progression of the disease. We will purify CLL cells and the other cellular components from the three compartments in which CLL cells are located, bone marrow, lymphonodes and peripheral blood. We will assess the expression of selected microRNAs in B-cells after cell-cell mediated interaction. These experiments will clarify if stimuli generated from the cellular cross-talk are responsible for the dysregulation of the microRNAs related to the clinical progression, and in which compartment these events could occur. CLL cells will also be stimulated with plasma from patients with CLL at different stage of progression to identify a possible role of the soluble/secreted molecules on the regulation of the expression of those microRNAs. Together, these findings will lead the discovery of novel mechanisms underlaid the progression of the CLL and will provide new therapeutic targets helping the management of patients with CLL.

Keywords: haematology,oncology,molecular biology
A Systems Biology approach to disclose auxin synthesis in plants (SYSBIOAUX)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Life-long training and career development
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2011-CIG, 2011)
Start date: 2012-03-01
End date: 2016-02-29
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Because plants have a sessile lifestyle, they must adjust to various external cues and coordinate their developmental program accordingly. To facilitate survival in often hostile environments, plants have evolved a notable developmental plasticity that allows them to shape their body and optimise their metabolism according to specific environmental demands. As with other multicellular organisms, the coordination of plant development relies on the communication across cellular boarders. In this context, plants employ a chemical-based network to control their developmental and physiological processes. Central to this network are a limited number of small molecules, called phytohormones. They are responsible for the adequate transcriptional reprogramming of tissues answering to external cues or for the maintenance of coordinated development. Although several molecules are known to function as plant hormones, plant shape is largely controlled by auxin. Over the past decades the knowledge of auxin action and signalling has greatly improved. By contrast, the synthesis of auxin is still not fully defined with respect to catalysed reactions and enzymes involved. Currently, it is assumed that a small number of alternative biosynthetic pathways contribute to auxin biosynthesis in plants. Due to prevailing knowledge gaps, extensive functional redundancy, and tissue and plant specific variations in expression patterns of the identified components, the relevance of each of these pathways is difficult to assess. The main focus of this project is to close the existing knowledge gaps and to decipher the pathways of auxin formation in plants. In addition, the cross-talk between the individual pathways and their regulation will be studied. To achieve these goals, a truly Systems Biology approach will be taken, encompassing genetics, transcriptomics, metabolomics, and bioinformatics workflows.

Keywords: plant physiology,plant development,plant growth,plant hormones,auxin,genetics,transcriptomics,metabolomics,bioinformatics,functional and relational network models
Integrated approaches for genomic variation discovery using high throughput sequencing (IAGVDHTS)

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: Türkiye
Call:  (FP7-PEOPLE-2011-CIG, 2011)
Start date: 2012-04-01
End date: 2016-03-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

The new sequencing technologies revolutionize genomics as they promise low-cost, high-throughput sequencing (HTS) of both new species and different individuals to better analyze the patterns of genetic variation. These “next-generation” platforms started to contribute our understanding of human genome diversity with the 1000 Genomes Project that employs the HTS methods to produce the most detailed map of human variation. Other large scale sequencing projects are being initiated to characterize genomes to assess characteristics of human genome diversity, to find genetic causes for disease, and infer the evolutionary history of species. Although we can now generate data at a rate previously unimaginable, the analysis of the data is proceeding at a slower pace as currently available algorithms to analyze HTS data show different biases against different classes of variation. There is a need to forge an alliance between computer science and genomics to devise better methods to use the massive amount of sequence data. Here we propose to develop novel algorithms to comprehensively and quickly discover all forms of genomic variants including point mutations, indel polymorphisms and structural variation while resolving inconsistencies among different variants to accurately identify normal and disease-causing variation. The proposed project, when completed, will help better make use of the data generated by the HTS platforms by enabling complete and accurate analysis of genomic variants in newly sequenced human individuals, and non-human organisms. Better analysis in a timely fashion also opens the way to discover more variants that might be medically relevant. Moreover, accurate and complete characterization of genomic variants within the most complex regions of the human genome may help solve the problem of “missing heritability” in complex disease that is not readily addressed by conventional genome-wide association studies.

Keywords: genomics,computational biology,bioinformatics