Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Application of MRI to explore myocardial structural reorganisation accompanying contraction and the influence of this on arrhythmogenesis the normal and post infarct heart. (MSIA)

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: France
Call:  (FP7-PEOPLE-2010-IEF, 2010)
Start date: 2012-05-01
End date: 2014-04-30
Duration (months): 24.0
Total project cost (EUR): 194564.0
EU funding (EUR): 194564.0
Participants: 1
Project status: CLOSED

Understanding of normal and abnormal cardiac excitation and contraction requires the integration of knowledge of myocyte electrophysiology and mechanics with knowledge of dynamic myocardial architecture. The myocardium is structured as stacked 4-6 cells thick (~100 µm) laminae of myocytes, which have a complex architectural arrangement throughout the cardiac wall and have localised regions of abrupt change in orientation. Ventricular structure is not an esoteric consideration of form. Along with other functional and structural properties of the myocardium, fibre and laminar architecture determine i) the spread of myocardial activation and ii) the deformation of the wall in contraction. My hypothesis is that: (i) myocardial systolic thickening is enabled by the sliding of sheets over each other, with the laminar architecture serving to limit shear stress; 2) that sheet sliding will have a role in electromechanical feedback which will influence the initiation, propagation and termination of arrhythmias; 3) that myolaminar sliding will be absent in infarct scars, with consequent large strain in the peri-infarct region and that this will have consequences for structural re-organisation, the propagation of activation and arrhythmogenesis in the surrounding myocardium. These hypotheses will be investigated using ex vivo and in vivo MRI of laminar structure with concurrent electrophysiological (EP) epicardial/endocardial recordings. The study has two phases: (Year 1) preclinical method development in isolated and in situ mouse hearts using high-field strength MRI spectrometers; (Year 2) a translational MRI and EP-mapping in a sheep chronic infarction model. Results will have implications for the fundamental understanding of myocardial architectural dynamics (between systole and diastole) and the role of this in electromechanical feedback, and furthermore, the results will have potential clinical applications.

Keywords: arrhythmia,myocardial structure,laminar structure
FUNCTIONAL GENOMICS STUDIES IN MARINE PRIMARY PRODUCTIVITY: ENVIRONMENTAL AND POLUTION EFFECTS ON PHYTOPLANKTON (GENMARPHYTO)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Outgoing Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France
Call:  (FP7-PEOPLE-2010-IOF, 2010)
Start date: 2012-09-01
End date: 2015-08-31
Duration (months): 36.0
Total project cost (EUR): 332702.5
EU funding (EUR): 332702.5
Participants: 1
Project status: CLOSED

One of the most serious challenges for humankind this century will be to understand how climate change (past, present and future) influences life in the oceans. It is known that marine phytoplankton carry out almost half of the global net photosynthesis of the planet. Therefore it will be essential to determine how climate change alters microbial metabolism. However, the integration of cell biology and genomics into oceanographic research is not sufficiently developed, even though biological (and especially microbiological) processes are fundamental for maintaining a functional biosphere. This project addresses the application of a novel molecular approach using genomics and metagenomics to elucidate metabolic activities under different conditions in the ocean in various groups of photosynthetic prokaryotes and eukaryotes. These techniques will also allow the rapid identification of candidate genes and facilitate the association of genes with specific metabolic and regulatory functions in different organisms spanning hundreds of millions of years of evolution. The initial phase of the project will investigate unicellular cyanobacteria using full genome microarrays analysis (outgoing). In a second phase, genomics studies will be done in diatoms, unicellular eukaryotes (return). The novelty of the proposed research lies in its interdisciplinary approach linking oceanography with cell biology and genomics. A key novel aspect of the proposal is the application of a comparative approach to very different groups of photosynthetic organisms, which will allow us to contrast the strategies of responses to environmental changes between them. This will improve our knowledge of the crucial roles marine microorganisms play in maintaining the well being of our planet. The successful implementation of the project will result in a substantial transfer of expertise from a world wide-leading centre in marine biology to the applicant and his team on return to a European institute.

Keywords: marine ecosystems (climate change),primary productivity,cyanobacteria,diatoms,microbial diversity,molecular ecology,microarray,qpcr
Functional analysis of dispersal mechanisms of fungal endophytes in a tropical lowland rainforest (ENDOPHYTE DISPERSAL)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Outgoing Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Belgium
Call:  (FP7-PEOPLE-2010-IOF, 2010)
Start date: 2011-08-01
End date: 2014-07-31
Duration (months): 36.0
Total project cost (EUR): 238840.4
EU funding (EUR): 238840.4
Participants: 1
Project status: CLOSED

Highly diverse communities of endophytic fungi ― fungi that colonize plant tissues without causing symptoms of disease ― live cryptically in all higher plants ranging from mosses to flowering plants. While knowledge of the biodiversity and biogeography of endophytes is rapidly increasing, the mechanisms that maintain their diversity and control their dispersal among plants in natural ecosystems are widely unknown. Specifically the concerted functions of mutualistic and antagonistic plant-insect interactions on endophyte diversity and dispersal are little understood. In a comparative approach using myrmecophytes (ant-plants) and closely related non-myrmecophytic plant species, the function of defending ants as well as insect pollinators and herbivores on endophyte dispersal will be analyzed in a Peruvian lowland tropical rainforest. This study will be the first ever to examine the dispersal ecology of fungal endophytes among plants while considering the function of mutualistic and antagonistic insects in a natural ecosystem. Applying next generation sequencing of endophytes from plant and insect samples collected at the study site together with isolating living endophytes for morphological and molecular characterization will permit the novel analysis of environmental and evolutionary factors influencing the diversity and community composition of these cryptic organisms. This project will use state of the art techniques in molecular community ecology and dispersal modeling and will address important questions of wide relevance for general distribution mechanisms of fungal endophytes. The proposed research will be combined with high quality training in population genetic and phylogenetic methodology, provided by world leading experts in these areas.

Keywords: natural sciences,endophytes,ecology,dispersal,multi-trophic interactions,tropical ecosystems,mutualism,insects,fungi,modeling,molecular analysis
Ultrafast Lasers and Attosecond Dynamics (ULAD)

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: Switzerland
Call:  (FP7-PEOPLE-2010-IIF, 2010)
Start date: 2011-04-01
End date: 2013-07-31
Duration (months): 28.0
Total project cost (EUR): 248905.0
EU funding (EUR): 248905.0
Participants: 1
Project status: CLOSED

Attosecond technology realizes the century-old dream of direct measurement of electron dynamics at the atomic scale. The ensuing experimental cornucopia, with many publications in Nature and Science, underscores the need for better analytic tools to explain the data, as a step towards a better physical foundation for a truly multi-disciplinary science. Current theoretical technique must be substantially improved to properly address some recent experimental controversies, such as measurements of quantum tunneling time. In particular, high harmonic generation (HHG), crucial to many experiments in attosecond science, requires a clearer "physical picture" than semi-classical models allow. A major goal of this proposal is to provide a theoretical framework for the experiments performed by Prof. Keller's group (ETH, Zurich) and others, and thereby to bring light to current debates. The research will develop analytic techniques to calculate quantum tunneling time in HHG, and better explain other steps of the HHG process, in particular the generation of attosecond pulses via quantum path interference and the interaction of the continuum electron with the laser pulse. The analysis will address both quantum and classical regimes of HHG: e.g., the quantum tunneling calculation will use a path integral approach, the interaction of the continuum electron with the laser field will employ plasma physics techniques, etc. Both of these approaches match well with the Fellow's background: the path integral approach was previously used to study escape from a potential well, and the Fellow's dissertation focuses on the interaction of charged particles with E&M fields. The project offers a possibility of close collaboration with the Fellow's graduate institution of Princeton University and other major research centers.

Keywords: attosecond dynamics,high harmonic generation (hhg),plasma physics,quantum tunneling experiments,ultrafast lasers,quantum path interference,nonlinear dynamics,atomic and molecular physics
Functional and structural analysis of the mammalian nonsense-mediated mRNA decay pathway (NMDPATHS)

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: 2012-06-01
End date: 2014-05-31
Duration (months): 24.0
Total project cost (EUR): 162242.4
EU funding (EUR): 162242.4
Participants: 1
Project status: CLOSED

Nonsense-mediated mRNA decay (NMD) is an important quality control pathway conserved throughout all eukaryotes: mRNAs which contain premature stop codons (PTC) are detected and committed to accelerated decay to protect the cell from deleterious effects of truncated proteins. NMD also controls abundance of many wild-type genes that contain features recognized by the NMD machinery. Due to the important tasks of NMD, its proper functioning is essential for embryogenesis in vertebrates. Furthermore, NMD plays a prominent role in carcinogenesis and is involved in several genetic disorders. The core NMD factors are identified and a picture of the steps involved is emerging. However, the exact interactions of the NMD factors, the order and orchestration of the processes, and the connection between PTC-recognition and mRNA decay remain unclear. In fact, detailed knowledge about NMD is necessary for drug development and more generally might reveal aspects of control and interactions in complex pathways that could be transferred to other systems. I will dissect the interactions between factors that come into play after PTC-recognition, namely Smg5, Smg6, Smg7, Upf1 and the phosphatase PP2A. First, I will define their interacting domains by co-immunoprecipitation from human cells. Subsequently, I will reconstitute the complexes in vitro, determine binding affinities and try to solve their crystal structure. Mutations that disrupt these complexes will be used to test their role in NMD in vivo. The effect of Upf1-phosphorylation on these interactions will also be investigated. Furthermore, I plan to identify factors that connect PTC-recognition to the general mRNA degradation machineries by a co-immunoprecipitation screen from human cells.

Keywords: natural sciences,biological sciences,biology,cell biology,molecular biology,structural biology,biochemistry
Determining novel peptide sequence and matrix mechanical properties to increase osteogenesis in embryonic stem cells using designer alginate hydrogels for bone regeneration (PEPTIDE OSTEOGEL)

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: 2011-03-01
End date: 2013-02-28
Duration (months): 24.0
Total project cost (EUR): 201049.6
EU funding (EUR): 201049.6
Participants: 1
Project status: CLOSED

Regenerating large bone defects is a great challenge in regenerative medicine. Embryonic stem cell (ESC) therapies are an attractive option due to their unlimited proliferation and ability to produce the cell types needed for bone repair. Here, we propose creating a three-dimensional alginate hydrogel that displays bioactive epitopes and has mechanical properties that induce osteogenic differentiation of ESCs and increase bone formation in vitro. We will do this by building upon previous research in the group of Prof Molly Stevens, which found that ESCs cultured on the extracellular matrix of bone forming osteoblasts increased both differentiation into osteogenic cells and bone formation. We propose using a proteomic approach to identify the proteins that are responsible for this effect. Once the proteins are known, they will be cut into short overlapping peptides that will be synthesized and attached to a cell culture surface. ESCs will then be grown on them to determine the sequences that induce osteogenesis. Using two-dimensional hydrogels of different stiffness that are coated with the osteogenic peptide, the mechanical properties that maximize osteogenesis will be determined. This peptide will then be coupled to alginate to form a hydrogel whose mechanical properties will be tailored to maximize bone formation. Novel sequences which induce osteogenesis are important to stem cell biology and an artificial matrix that differentiates ESCs into osteoblasts using both displayed ligands and stiffness would be important to regenerative medicine. The project Peptide Osteogel will be beneficial to Europe by bringing a scientist with a unique skill set into a top biomaterials lab to work on a multidisciplinary project that will increase the quality and status of science in the European Union. This fellowship will enable greater collaboration and transfer of knowledge across Europe, increasing the mobility and human potential of scientists across the continent.

Keywords: biomaterial engineering,embryonic stem cells,bone,osteogenesis,differentiation,peptide,alginate,mechanical properties
NATURE’S FIRST LEAD IN THE FIGHT AGAINST MESOTHELIOMA: THE TOTAL SYNTHESIS AND BIOLOGICAL EVALUATION OF JBIR-23 AND RELATED COMPOUNDS (JBIR-23)

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: 2011-06-13
End date: 2013-06-12
Duration (months): 24.0
Total project cost (EUR): 200549.6
EU funding (EUR): 200549.6
Participants: 1
Project status: CLOSED

Human malignant pleural mesothelioma is an aggressive (fatal) lung cancer which is always associated with previous asbestos exposure. Typically symptoms do not appear until 35-40 years after the original exposure, with life expectancy then 12-18 months. Given the great use of asbestos during the 20th century (before its long overdue ban in 1985) and this long latency period, it is no surprise that cases of mesothelioma continue to rise. There is no known cure for mesothelioma: traditional chemotherapeutic cancer treatments have had little impact on the disease and radiotherapy or partial pleurectomy have only very limited impact on life expectancy. However, very little in the way of mesothelioma research is taking place, as it is frequently not considered to be a ‘big enough market’ (<1% of all cancers in the U.K.) and consequently there are currently no drugs in development for this disease. A second reason for this is that there have been no reported good lead compounds (natural products) as a starting point for the drug discovery process. Until now. First isolated from Streptomyces sp. AK-AB27 in 2008, JBIR-23 possesses a unique structural architecture, hitherto unobserved in Streptomyces extracts. Furthermore, JBIR-23 is unique, in that it is the first natural product to be isolated to exhibit activity against human malignant pleural mesothelioma. This is an amazing breakthrough: the isolation of the first natural product to be highly active against mesothelioma is crucial, providing a precious lead compound for investigation. The aim of the project, therefore, is to investigate the synthesis and anti-mesothelioma activity of JBIR-23 and to prepare further analogues to commence structure-activity studies. This will be the first study of this kind.

Keywords: organic chemistry,heterocyclic chemistry,total synthesis,mesothelioma
The energy Landscapes of metastable states of supercooled liquids (EL-GLASS)

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: 2011-08-08
End date: 2013-08-07
Duration (months): 24.0
Total project cost (EUR): 203049.6
EU funding (EUR): 203049.6
Participants: 1
Project status: CLOSED

Recently it has become generally accepted that a root cause of the divergently slow dynamics of glassy liquids is the tendency of the molecules to become stuck in metastable configurations (states). This effect leads to an increasing separation of time scales between local vibrational motion and larger scale molecular reconfiguration. We will use state-of-the-art geometry optimisation techniques along with large scale molecular dynamics simulations to explore the energy landscape that supports these metastable states, focusing in particular on the escape mechanism from such traps. We will frame our investigation around the use of a reaction coordinate which measures proximity to a given metastable state. The order parameter will be realized in several ways: as the liquid's structural overlap with a metastable molecular configuration, and as the size of a mobile droplet in an environment of immobile molecules taken from a given metastable configuration. We will test whether these reaction coordinates are meaningful order parameters. We will further examine how the static energy landscape and the dynamics are dependent on the reaction coordinate, and how changes in the former are realized in the latter. Our results will be a stringent test for many contemporary theories of the glass transition by scrutinising the concept of a metastable state, by characterising escape mechanisms, and by demonstrating how these paths define the organisation of the underlying energy landscape. Our use of appropriately derived order parameters will greatly reduce the relevant phase space that needs to be considered, and will be combined with cutting edge methodology for constructing equilibrium densities of states and for rare event dynamics to examine the thermodynamic and dynamic properties at low temperatures. This approach should produce definitive and unambiguous results that should greatly strengthen the foundations of our understanding of glassy dynamics.

Keywords: computational physics,statistical physics,soft matter and polymer physics,chemical physics
Understanding the effects of influenza hemagglutinin mutations on viral membrane fusion (INFLUENZA FUSION)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Outgoing Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Sweden
Call:  (FP7-PEOPLE-2010-IOF, 2010)
Start date: 2012-01-01
End date: 2015-08-01
Duration (months): 36.0
Total project cost (EUR): 228104.8
EU funding (EUR): 228104.8
Participants: 1
Project status: CLOSED

Membrane fusion is a critical step in cellular entry and infection by enveloped viruses such as influenza. Influenza hemagglutinin catalyzes fusion by interacting with membrane lipids, but the nature of this interaction is not well understood. Experimental mutagenesis has yielded much data on the functional requirements of the proteins that catalyze fusion, but we have no robust theory that could have predicted these results. Developing a drug that inhibits viral entry has long been a goal, but high-affinity inhibitors have been challenging due in part to a lack of knowledge regarding important structural intermediates in viral membrane fusion. This proposal aims to aid target identification by developing robust mechanistic models of influenza viral entry. This structural information has previously been challenging for both experimental and computational methods. Traditional crystallographic methods are hampered by the dynamic processes involved and the intimate involvement of the membrane environment. We have developed new computational methods and platforms that allow the simulation of large membrane assemblies on the timescales required to examine fusion mechanisms. We will simulate fusion both by native influenza hemagglutinin and by a series of mutants, matching these simulations against the results of cell-fusion assays. This approach will allows us to predict fusion protein structures and dynamics at high resolution while validating our simulations against experimental data. Using this combined approach, we hope to shed light on influenza fusion mechanisms and elucidate future antiviral drug targets.

Keywords: computational biology,structural biology,virology