Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
MARKER-BASED, 3-D ADAPTIVE CARTESIAN GRID METHOD FOR MULTIPHASE FLOW AROUND IRREGULAR GEOMETRIES (CART3DADAPT)

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: Türkiye
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2012-02-08
End date: 2016-02-07
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Computational simulations of multiphase flow are challenging because many practical applications require adequate resolution of not only interfacial physics associated with moving boundaries with possible topological changes, but also around three-dimensional, irregular solid geometries. This project focuses on the simulations of fluid/fluid dynamics around complex geometries, based on an Eulerian-Lagrangian framework. The approach envisions using two independent but related grid layouts to track the interface and solid boundaries. In particular, the stationary Cartesian grid with automated local adaptive refinement capabilities is to handle the computation of the transport equations, while the interface shape and movement are treated by marker-based triangulated surface meshes which freely move and interact with the Cartesian grid. The markers are also used for identifying the location of the solid boundaries and enforcing the no-slip condition there. Issues related to the contact line treatment, topological changes of multiphase fronts during merger or breakup of objects, and necessary data structures and solution techniques will be investigated. Validation studies will be carried using (i) interface in a time-reversed vortex field (ii) effect of spurious currents (iii) Buoyancy driven rising bubble (iv) Drop impacting on a flat surface (v) Binary drop collision.

Keywords: computational physics,computational fluid dynamics,3 d modelling,computational models,engineering mathematics,multiphase flows
Marine Amino Acid Racemisation Investigation of the Mediterranean (MAARITIME)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: European Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2010-10-01
End date: 2013-09-30
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

mAARiTIME is a highly interdisciplinary project, which brings together the fields of Archaeology, Biology, Chemistry, Geochronology and Quaternary Sciences. Through protein geochronology (amino acid racemisation dating, AAR), it seeks to answer two specific but vital questions: when did early humans become “modern”, and is “modern” behaviour unique to our own species? Behavioural modernity has fortuitously left traces in the archaeological record as molluscan remains, one of the best substrates for AAR dating. Molluscs were exploited as a food resource and shells were used as personal ornaments, providing some of the earliest evidence of symbolic thinking displayed by early humans. These appear between 160-70 ka ago, a period which falls tantalisingly outside that of many commonly applied dating techniques. AAR is able to yield direct age information for mollusc shells, and its broad temporal span (the whole Quaternary, 0-2.6 Ma) makes it the ideal method for framing chronologically the debate over the origins of modern human behaviour. mAARiTIME will focus on the Mediterranean rim, which is key to the development of behavioural modernity. By applying a novel (closed-system) method of AAR dating, mAARiTIME will build chronological frameworks able to provide reliable dating control for this area. The method will be rigorously tested by laboratory experiments on different molluscan taxa as well as by comparing the AAR data with independent age information. A detailed investigation of protein breakdown will also be performed by applying state-of-the-art proteomics and imaging techniques. Other than producing important advances in geochronology and archaeological sciences, mAARiTIME will enable the development of long-lasting collaboration between a network of researchers in Northern and Southern Europe, coordinated by the applicant, and with the long-term goal of establishing a AAR dating facility in Southern Europe.

Keywords: bioarchaeology,amino acid racemisation,geochronology,human evolution,modern behaviour,mediterranean,marine molluscs,protein diagenesis,cave deposits,palaeolithic
Genome-wide study of human epigenetic regulators (EPIX)

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: France
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2010-09-01
End date: 2014-08-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Epigenetics is a new frontier in biology. It has yielded revolutionary insight into how the genome works, and has profound implication for human health. This project focuses on the best-established epigenetic mark, DNA methylation. This mark is essential for the embryonic development and adult life of mammals, and acts primarily by regulating gene expression. While the essential functions of DNA methylation are well-known, our knowledge of its effectors is very limited. Nine mammalian proteins are known to recognize methylated DNA and regulate gene expression, but each has so far been studied in isolation, and on a very small portion of the genome. We want to describe the full landscape of DNA methylation in human cells by studying all 9 known proteins in parallel in a unified experimental system, using genome-wide approaches. Briefly, all proteins will be used in chromatin- immunoprecipitation followed by massive sequencing (ChIP-SEQ), in the human cell line K562. We will validate the identified patterns by directed approaches, submit them to an extensive bio-informatic analysis, and compare them to the distribution of DNA methylation, modified histones, transcription factors, and cofactors that have been and are being identified in this cell line. Biological hypotheses will be drawn from the results and tested experimentally in K562 and in non-transformed cells. Our data will yield the first integrated view of DNA methylation, its targets, and its effectors, in human cells, and will provide a quantum leap over the existing state of the art. The project will advance basic research, and will also likely prove useful in medicine.

Keywords: genomics
Genome Evolution in the Animal Kingdom (GENEVA)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Genetics, Genomics, Bioinformatics and Systems Biology
Countries involved: United Kingdom
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-06-01
End date: 2016-05-31
Duration (months): 60.0
Total project cost (EUR): 1735016.0
EU funding (EUR): 1735016.0
Participants: 1
Project status: CLOSED

Like everything in biology, the genome is a product of evolution. In our own history, mutations that duplicate genes have generated extensive multigene families and classes, including a great diversity of transcriptional regulators involved in development of cells, tissues and organs. For example, two complete genome duplication events occurred in early vertebrate evolution (known as 2R), a third genome duplication occurred at the base of teleost fish (3R), and there were extensive tandem gene duplications in placental mammals. What role did these events play in animal evolution? How do newly duplicate genes diverge in function? Why do tandem gene duplicates evolve in a different way to whole genome duplicates? The proposed research programme aims to resolve these questions. The long-term functional consequences of duplication will be examined by examining how the spectrum of target genes differs, or overlaps, between transcription factors known to have duplicated in the 2R and 3R events. To understand the earliest stages of duplicate gene evolution gene sequences and gene expression will be studied in a spectrum of animals descendent from much more recent genome duplications, including several freshwater fish and desert-living rodents. The contrast between whole genome and tandem gene duplication will be examined in parallel, through genomic and protein-engineering studies of novel homeobox genes that arose in mammalian evolution. The programme of research is novel and will create physical and knowledge-based resources relevant to genomics, evolution, development, physiology and biomedical genetics.

Keywords: molecular evolution,gene duplication,homeobox,vertebrate,gene family
The population biology of drug resistance: Key principles for a more sustainable use of drugs (PBDR)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Evolutionary, population and environmental biology
Countries involved: Switzerland
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-07-01
End date: 2017-06-30
Duration (months): 72.0
Total project cost (EUR): 2272403.0
EU funding (EUR): 2272403.0
Participants: 1
Project status: CLOSED

The evolution of drug resistance and its control represents a considerable challenge in very different biological contexts ranging from pesticide resistance in agriculture to antimicrobial resistance in clinical settings and even extends beyond infectious pathogens, as resistance also evolves in cancer chemotherapy. Naturally, the recommendations for the optimal use of drugs to minimise resistance differ for different biological contexts. In some cases, similar strategies for vastly different pathogens or biological contexts are recommended, whereas in other cases opposing strategies for similar pathogens are advised. To which extent these discrepancies in treatment recommendations are attributable to specific properties of the pathogen, the host, or the general biological context is currently unclear. The aim of this proposal is to develop an integrative population biological framework for the evolution of resistance and its control. To this end we will develop mathematical models of resistance evolution in viruses, bacteria, parasites, cancer and fungal plant pathogens. Developing detailed population biological models that account for the specific biology of these ¿pathogens¿ as well as the specific context of the application of drugs will allow us to identify those aspects that are common between different biological contexts and those aspects that are specific to the pathogen, the host or the drug. Moreover, working simultaneously on resistance evolution in these different biological contexts will facilitate the translation of findings between fields of research that to date have remained largely separate. We seek to bridge these fields and integrate insight to develop a broad conceptual framework with which to address the ever-growing problem of sustainable drug use.

Keywords: drug resistance,mathematical models
Unravelling oncogenic defects in feedback control of receptor tyrosine kinases (ONCROBUST)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: ERC Advanced Grant Interdisciplinary Panel
Countries involved: Israel
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-08-01
End date: 2016-07-31
Duration (months): 60.0
Total project cost (EUR): 2228180.0
EU funding (EUR): 2228180.0
Participants: 1
Project status: CLOSED

Cellular growth and migration depend on intracellular communication webs mediated by polypeptide growth factors. One example comprises EGF-like growth factors and their ErbB receptor tyrosine kinases. EGFR and HER2 are frequently involved in cancer progression, and they serve as targets for cancer therapeutics. The existence of a kinase-dead receptor, as well as the emergence of resistance in patients treated with EGFR and HER2 blockers, instigated a paradigm shift from a linear EGF-to-ErbB cascade to a robust network characterized by multiple feedback loops. We assume that deregulation of feedback loops plays essential roles in human cancer. Because of the abundance of feedback regulation, we predict subtle, multi-component impact on disease. Aiming at the natural richness of feedback regulation in breast cancer, we will develop in vitro models of normal mammary cells, and introduce genetic, disease-mimicry manipulations. Two time domains of feedback regulation will be addressed: (i) the early domain of post-translational modifications, which we will explore using proteomic approaches. And (ii) the late domain comprising alterations in transcription, micro-RNAs and alternative splicing, processes we will investigate using deep sequencing and array technologies. Once verified and characterized in normal cells, we will survey the operational status of the unravelled feedback loops in genetically manipulated cell systems and in tumour specimens, using immunological and bio-informatical approaches. Detailed knowledge of feedback regulation of multi-layered signalling networks, such as ErbB, is expected to shed light on the currently elusive basis of signal integration and elimination of noise, as well as identify markers of prognosis.

Keywords: growth factor,tyrosine kinase,signal transduction,network biology,cancer
Exploring novel pathways governing immunity and leukemia by studying the genetic basis of human myeloid cell defects - from genetics to gene therapy (EXPLORE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Immunity and infection
Countries involved: Germany
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2012-01-01
End date: 2017-06-30
Duration (months): 66.0
Total project cost (EUR): 2496648.0
EU funding (EUR): 2496648.0
Participants: 1
Project status: CLOSED

Genomic system biology approaches offer new aspects to understand the basis of diseases and to develop new therapeutic strategies. Here, we propose to study rare human variants of the immune system to provide novel explanations of mechanisms governing inflammation and leukemogenesis. Following a full circle of translational research, our group has previously defined several novel clinical entities and elucidated their molecular defects (Nat Med 2007, NEJM 2009). Further studies have highlighted the critical role of new pathways for general biological principles (Immunity 2005, Nat Gen 2007, Nat Med 2008). Finally, we have developed innovative gene and cell-based therapeutic strategies and tested their feasibility in clinical trials (JCO 2007, NEJM2009). The overall goal of ¿Explore¿ is to decipher novel pathways controlling myeloid cell function and leukemogenesis. The following specific aims are proposed: 1. To elucidate genetic defects causing neutrophil disorders in children by homozygosity mapping and to perform functional studies in vitro and in vivo using relevant animal models 2. To identify novel genes controlling endoplasmic reticulum cell function and the secretory pathway in myeloid cells by employing RNA-interference technology 3. To define the role of novel factors involved in controlling the topology of the endoplasmic reticulum and ER-stress in murine model systems 4. To study the role of HAX1 in hematopoisis and leukemogenesis using a new murine HAX1flox allele and to develop a clinical gene therapy approach for patients with severe congenital neutropenia due to HAX1-deficiency These studies will not only identify novel genetic factors controlling human immunity and leukemogenesis, but may ultimately impact on the development of novel therapeutic strategies.

Keywords: neutrophils,primary immunodeficiency disorders,vesicular trafficking,endoplasmic reticulum stress,gene therapy
Spatial protein quality control and its links to aging, proteotoxicity, and polarity (QUALIAGE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: Sweden
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-06-01
End date: 2016-05-31
Duration (months): 60.0
Total project cost (EUR): 2371262.0
EU funding (EUR): 2371262.0
Participants: 1
Project status: CLOSED

Propagation of a species requires periodic cell renewal to avoid clonal senescence. My laboratory has described a new mechanism for such cell renewal in yeast, in which damaged protein aggregates are transported out of the daughter buds along actin cables to preserve youthfulness. Such spatial protein quality control (SQC) is a Sir2p-dependent process and by establishing the global genetic interaction network of SIR2, we identified the polarisome as the machinery required for mitotic segregation and translocation of protein aggregates. In addition, we found that the fusion of smaller aggregates into large inclusion bodies, a process that has been suggested to reduce the toxicity of such aggregates, requires actin cables and their nucleation at the septin ring. Sir2p controls damage segregation by affecting deacetylation and the activity of the chaperonin CCT, enhancing actin folding and polymerization. Considering that CCT has been implicated in mitigating aggregation/toxicity of polyglutamine proteins, e.g. huntingtin, and that actin cables is affecting formation, fusion, and resolution of aggregates, we hypothesize that CCT deacetylation may underlie Sirt1¿s (mammalian orthologues of Sir2p) documented beneficial effects in several neurodegenerative disorders caused by proteotoxic aggregates. This project is aimed at approaching this hypothesis and to elucidate, on a genome-wide scale, how the cell tether, sort, fuse, and detoxify aggregates with the help of CCT, actin cables, and the polarity machinery. This will be accomplished by combining the power of synthetic genetic array analysis, high-content imaging, genome wide proximity ligand assays, and microfluidics. Using such approaches, the project seeks to decipher the machineries of the spatial quality control network as a means to identify new therapeutic targets that may retard or postpone the development of age-related maladies, including neurodegenerative disorders.

Keywords: aging,genetic array analysis,proteotoxicity,protein aggregation,spatial quality control,cell polarity
Regulating recombination in mitotic and meiotic cells (RECMITMEI)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Genetics, Genomics, Bioinformatics and Systems Biology
Countries involved: United Kingdom
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2016-04-30
Duration (months): 60.0
Total project cost (EUR): 2379103.6
EU funding (EUR): 2379103.6
Participants: 2
Project status: CLOSED

DNA is a highly reactive molecule that is subject to deliberate, spontaneous and environmental damage. One of the most catastrophic lesions in DNA is the double-strand break (DSB), which if left unrepaired can result in cell death, infertility, genome instability and cancer. Homologous recombination (HR) is a largely error-free mechanism of DSB repair that utilizes an intact sister or homologous chromosome as a repair template. Despite considerable progress in understanding the mechanisms of HR, very little is known about how this process is regulated. My lab has made a number of seminal discoveries that have improved our understanding of how HR is regulated in mitotic and meiotic cells. In this ERC proposal, we plan to elucidate the mechanisms that control HR events in mitotic cells and regulate HR pathway choice during meiotic recombination. We will place particular emphasis on defining the roles of RTEL1 and HELQ1 in regulating HR in mitotic and meiotic cells and will determine how dysfunction of these genes contributes to tumorigenesis. Biochemistry and proteomic approaches will be employed to determine how the Fanconi anemia (FA) pathway counteracts error-prone repair by non-homologous end joining (NHEJ), thus favouring HR repair in S-phase. The use of NHEJ inhibitors as a potential treatment of FA will be tested in existing mouse models of FA. Finally, genetic screens and proteomic analysis of HR regulators will be performed in C. elegans to elucidate the mechanisms that regulate the choice between crossover and non-crossover pathways during meiotic HR. Thus, in the work proposed here, my lab will make use of multiple experimental approaches to elucidate the mechanisms for control of HR and the consequences of dysregulated HR on human disease.

Keywords: meiosis,recombination,tumorigenesis,dna repair
Collective scattering of light (COSCALI)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Research Staff Exchange Scheme
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Germany,France,Italy
Call:  (FP7-PEOPLE-2010-IRSES, 2010)
Start date: 2011-04-01
End date: 2015-03-31
Duration (months): 48.0
Total project cost (EUR): 86100.0
EU funding (EUR): 86100.0
Participants: 3
Project status: CLOSED

The proposed research network will investigate collective scattering of light from cold clouds of atoms in various complementary situations. To these belong photonic bandgaps in optical lattices, magneto-optic traps, atoms within dipole traps, quantum gases in high-finesse ring cavities and Bose-condensates with vortices. These systems provide ideal toy models for a whole class of phenomena occuring in the interaction between light and matter. In particular, they allow to investigate different aspects of collective light scattering which ultimately will lead to a complete understanding of the topic. Questions on the roles of cooperativity and self-organization of the scatterers, disorder and turbulence in the system, quantum effects in the ensembles, multiple scattering and Anderson localization of photons, super- and sub-radiance of the emitted light, and entanglement between light and matter will be addressed by theory and experiment, and new techniques for measuring and analyzing collective light scattering will be developed. Both experimental and theoretical groups located in Europe and Brazil will work together to develop a thorough understanding of how light interacts with a collectivity of atoms.

Keywords: quantum gases,bose-einstein condensates,cold atoms,atomic physics,hydrodynamics,nonlinear physics,collective effects,self-organization,anderson localization,vortices,optical cavities