Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
A genome wide association study of the relationship between BMI, type II diabetes and recurrent depression (GWAS BMI T2D AND DEP)

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-IEF-2008, 2008)
Start date: 2009-03-02
End date: 2011-03-01
Duration (months): 24.0
Total project cost (EUR): 171867.63
EU funding (EUR): 171867.63
Participants: 1
Project status: CLOSED

Major or unipolar depression (UPD) is a major public health problem and cause economic negative consequences in industrialized countries (Hu,2006). Genetic studies offer an important route to understanding its causes. The inheritance of UPD is complex (Levinson,2005) and involves and inter-play of genetic and environmental factors (Farmer &amp; McGuffin,2003;Cervilla et al,2007). There has been a small number of linkage scans. McGuffin and colleagues (2005) reported a genome-wide linkage scan in the first wave of the GlaxoSmith-Kline DeNt Study of 438 affected sib pairs with recurrent UPD. The aim of the proposed work is to investigate genetic overlap between Body Mass Index (BMI), diabetes type 2 ‘metabolic syndrome’ and recurrent UPD. Some recent studies support the hypothesis that there may be shared aetiological factors between recurrent UPD, obesity and physical disorders (Farmer et al,2008;Patten et al,2005). In the course of an ongoing genome-wide association (GWA) study of recurrent UPD, McGuffin and colleagues have collected a wealth of detailed data on chronic co-morbid physical diseases such as obesity, diabetes, heart disease and migraine on both depressive cases and controls. The availability of such information will enable the hypothesis of a genetic overlap between depression and elevated BMI to be explored comprehensively. Therefore we will 1) explore whether polymorphisms in known ‘obesity genes’ FTO and MC4R differ in frequency between depression cases and controls, 2) explore the entire dataset for novel genes associated with BMI, 3) search for SNP associations with the combined phenotype of high BMI/depression, 4) follow up the top 10 ‘hits’ with re-genotyping and/or deep sequencing. The study capitalises on several large case collections with closely comparable data and will use the most cost effective method of examining a large number of SNPs and CNVs at a time when similar studies on other common disorders are yielding exciting novel results

Keywords: neurosciences,psychiatry,molecular genetics,recurrent unipolar depression,genome wide association studies (gwas)
Development of the Cephalochordate amphioxus, Branchiostoma lanceolatum, as a new model for regeneration (AMPHIREG)

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-IEF-2008, 2008)
Start date: 2009-04-15
End date: 2011-04-14
Duration (months): 24.0
Total project cost (EUR): 152401.03
EU funding (EUR): 152401.03
Participants: 1
Project status: CLOSED

While the ability to regenerate lost body parts or organs is legendary in invertebrates like echinoderms, chordates-and mammals in particular-have quite limited regenerative ability. The exceptions par excellence are salamanders, which can regenerate lens, limbs and tails. Unfortunately, vertebrate models of regeneration are costly to maintain, suffer from necessary ethical considerations, and are often plagued by duplicated genes, hindering functional analyses. The invertebrate cephalochordate amphioxus is the most basal chordate. It is characterised by a prototypical genome, ancestral chordate morphology, and lacks the whole-genome duplications characteristic of vertebrates. With sequencing of the genome, it is therefore an excellent model for evolution of developmental mechanisms from an invertebrate ancestor. Until now, there has been no convincing evidence of regeneration in a cephalochordate. However, the candidate’s preliminary data indicate that amphioxus can regenerate all structures of the tail, including neural tube, notochord and muscle. The purpose of the proposed research is to develop the European amphioxus, Branchiostoma lanceolatum, as a new regeneration model. The ojectives are: 1. To characterise proliferation and stem cells during regeneration; 2. To evaluate whether the signalling pathways responsible for vertebrate regeneration are conserved in amphioxus, specifically TGFb and Wnt; 3. To determine whether matrix metalloproteinases are implicated downstream of these pathways during tissue remodelling; 4. To develop electroporation or explant culture methodologies to knock down gene function; 5. To assess the level of conservation of regeneration mechanisms in deuterostomes by comparing with echinoderms. The workplan will include bio-informatics, in situ hybridisation, immunohistochemistry, confocal microscopy and pharmacological treatments. This research may have implications for regenerative and stem cell therapy and tissue engineering.

Keywords: regeneration,amphioxus,tgf-beta,wnt,matrix metalloproteinase
Maintenance of cellular memory by the Arabidopsis VRN1 protein (VRNEPIGEN)

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-IEF-2008, 2008)
Start date: 2009-03-01
End date: 2011-02-28
Duration (months): 24.0
Total project cost (EUR): 179649.73
EU funding (EUR): 179649.73
Participants: 1
Project status: CLOSED

Modifications of a cells chromatin landscape enable cells to memorize and maintain gene expression profiles throughout many cell-cycles during development. In animals and plants the Polycomb Repressive Complex 2 (PRC2) is involved in maintaining genes in an epigenetic “off” state. In mammals and flies a second complex, PRC1, collaborates with PRC2 to maintain silencing. Interestingly, other organisms including worms and plants lack PRC1 and it remains elusive how they achieve stable silencing. In Arabidopsis the DNA-binding protein VRN1 is a potential candidate to fulfil such a role in silencing. During a cold-induced process called vernalization, the floral repressor gene FLC is epigenetically repressed and maintained inactive by a plant PRC2 and VRN1. Lack of VRN1 does not impair PRC2 function but seems to act downstream or in parallel of PRC2, a situation analogous to animal PRC1. Moreover, as found for mammalian PRC1, VRN1 interacts with a component of the spliceosome complex, implying RNA processing in Polycomb silencing. The above findings suggest that VRN1, despite its lack of homology with PRC1 components, functions in the stable maintenance of PRC2 mediated silencing. My aim is to establish a solid foundation for a mechanistic understanding of VRN1 mediated gene silencing using vernalization as a model. In-depth VRN1 protein-complex analysis will be complemented by chromatin and RNA immuno-precipitations (ChIP and RIP) as well as theoretical modelling of the vernalization process. Besides addressing a long-standing question in plant epigenetics, collected data will allow comparison with the situation in non-plant systems to develop a mechanistic consensus model on maintenance of gene silencing in different kingdoms. Notably, for both plants and humans, fundamental knowledge of epigenetics will facilitate the modulation of gene expression to; increase yield and disease resistance in crops and develop treatments for diseases, such as cancer, in humans.

Keywords: arabidopsis,vernalization,vrn1,epigenetics,polycomb group,chromatin,histone modifictions,proteomics,flc,prc2
Evolution and function of the Blastocytis mitochondrion-like organelle (BHMLOEVOFUNC)

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: Czechia
Call:  (FP7-PEOPLE-IOF-2008, 2008)
Start date: 2010-02-01
End date: 2013-01-31
Duration (months): 36.0
Total project cost (EUR): 211218.14
EU funding (EUR): 211218.14
Participants: 1
Project status: CLOSED

Blastocystis is a unicellular human intestinal parasite, of controversial pathogenicity, that belongs to a diverse eukaryotic phylum called the Stramenopiles. Since Blastocystis is a strict anaerobe, it was thought that it might possess hydrogenosomes, anaerobic ATP-generating organelles related to mitochondria. In contrast to typical hydrogenosomes, Blastocystis has mitochondrion-like organelles (MLOs) with cristae, a transmembrane potential and DNA. Recent work has demonstrated a mitochondrial genome and bioinformatics analyses of expressed sequence tags (ESTs) have identified 115 putative mitochondrial and hydrogenosomal proteins. Amongst these was [FeFe]-hydrogenase, a hydrogenosomal marker protein that was shown to be localized to the MLOs. The organelles are also predicted to have canonical mitochondrial pathways for amino acid metabolism, iron-sulphur (Fe-S) cluster biogenesis and an incomplete tricarboxylic acid cycle. These data suggest that Blastocystis MLOs may be some kind of metabolic intermediate between mitochondria and hydrogenosomes. To test the predicted functions of these MLOs, I will immunolocalize and functionally characterize components of several of its predicted pathways including Fe/S cluster biosynthesis, amino acid metabolism and mitochondrial import. Furthermore, I will purify the Blastocystis MLOs for in vivo assays and proteomic analyses. With these methods I aim to identify the biochemical raison d’être of the mitochondria-like organelle for the parasite. By comparing its pathways with those in other eukaryote lineages, I will determine: (1) the unique biochemical properties of Blastocystis MLO, (2) how Blastocystis MLOs have adapted to an anaerobic and parasitic lifestyle, and (3) how environmental stimuli affect the metabolism of these MLOs. This project will provide basic information on the essential functions mitochondria across eukaryotic diversity as well as illuminate the metabolic plasticity of these fundamental organelles.

Keywords: molecular evolution,parasitology,protistology,phylogeny,cell biology,microbiology,evolutionary biology,computational biology
High-resolution quantitative climate reconstructions for understanding current trends: the past 2000 years of Tasmanian climate variability (TASCLIM)

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-IIF-2008, 2008)
Start date: 2009-06-01
End date: 2011-05-31
Duration (months): 24.0
Total project cost (EUR): 183069.48
EU funding (EUR): 183069.48
Participants: 1
Project status: CLOSED

The last 2000 years form a critical period in global climate history. They span a significant length of time prior to major anthropogenic influences on climate and include the shift to industry-based societies. Lack of data from the Southern Hemisphere limits our understanding of climate change and ability to differentiate and delineate interactions between natural, forced and stochastic variability. High-resolution data spanning the last 2000 years from key locations in the Southern Hemisphere are urgently needed to advance climate research globally. Tasmania is a key location for climate studies. The climate is dominated by the Southern westerlies and influenced by the El Nino Southern Oscillation and Southern Annular Mode. Previous palaeoclimate work has demonstrated records contain a genuine Southern Hemisphere climate signal. In-situ multi-channel reflectance spectroscopy (RS) is a novel approach for reconstructing temperature and precipitation from lake sediments. A series of lake sediment cores will be collected along the dominant climate gradient in Tasmania (west-east). In-situ RS in combination with high-precision chronologies developed using 210Pb and 14C will be used to reconstruct temperature and precipitation over the last 2000 years. TASCLIM is the first study of its kind in the Australasian region. It will produce high-resolution quantitative climate reconstructions with known uncertainties, significant new data and contribute to better understanding of regional, inter-hemispheric and global climate change and dynamics. The University of Bern and related institutional networks (OCCR, NCCR Climate, IGBP-PAGES) offer world-class facilities with a unique range of scientific expertise and excellent network for scientific exchange and transfer of knowledge. TASCLIM directly contributes to European and international programs, while providing a framework for the researcher to develop an independent scientific career and basis for long-term collaboration.

Keywords: natural sciences,climate variability (climate change),paleoclimate (climate change)
An Evolutionary Approach to Biodiversity Conservation: Riverine Floodplains of the European Alps as a Model System (FLOODPLAINEVOLUTION)

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: Germany
Call:  (FP7-PEOPLE-IIF-2008, 2008)
Start date: 2010-04-01
End date: 2012-03-31
Duration (months): 24.0
Total project cost (EUR): 170418.35
EU funding (EUR): 170418.35
Participants: 1
Project status: CLOSED

The importance of evolutionary relatedness of species is increasingly recognized in both ecology and conservation. What remains is a need for quantitative predictions on the role of evolution and a synthesis of methods. This project uses DNA surveys of aquatic insect communities to measure species diversity and genetic relatedness in riverine floodplains. Riverine floodplains are one of the most biodiverse ecosystems on earth and create a very high spatio-temporal heterogeneity. Unfortunately, the most diverse and abundant aquatic insects are poorly known at the species level, therefore research that has been carried out to link biodiversity and the spatio-temporal heterogeneity relies on estimates of diversity and has lacked an evolutionary perspective. The project examines the role of habitat heterogeneity in the evolutionary processes of structuring biodiversity by sampling communities from 4 habitat types at each of 6 study reaches along 3 natural riverine corridors in the Alps. It will construct a ‘DNA profile’ of macroinvertebrate communities using DNA sequences and coalescent-based modeling to delineate species, determine the extent of local and regional endemism of species, reconstruct a phylogeny of all samples and calculate phylogenetic diversity of individual habitats, individual reaches, and whole river corridors, and use the resulting tree topology to examine the degree of phylogenetic clustering and overdispersion as a means to quantify the role of evolution in community assembly. The project explores 3 timely research topics: the linkage of ecology and phylogeny, the integration of evolutionary criteria in conservation management, and DNA-based biodiversity surveys. The applicant has high potential for knowledge transfer to the European freshwater science and the implementation of the project. His expertise in river ecology and population genetics, problem-oriented approach as an engineer by training, and international experience will ensure success.

Keywords: evolutionary biology,biodiversity inventory: systematics phylogeny taxonomy,aquatic ecology,causes and mechanisms of loss,molecular genetics,biodiversity characterisation,freshwater ecology
Photoregulated organocatalysis - From caged catalysts to photoswitchable catalytic systems (PHOTORCA)

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-IEF-2008, 2008)
Start date: 2009-04-01
End date: 2011-03-31
Duration (months): 24.0
Total project cost (EUR): 160996.91
EU funding (EUR): 160996.91
Participants: 1
Project status: CLOSED

The project combines the two recent and versatile methodologies of organocatalysis and photoregulation with the objective to develop photoregulated organocatalytic systems. Together with the proposed immobilization in order to recycle these innovative catalysts such systems are expected to be of great value in the context of sustainable chemistry as control of reactions should allow for minimizing the formation of byproducts and therefore should create more efficient synthetic processes. If compared to highly efficient and selective enzymatic transformations, organocatalysis as their “biomimetic counterpart” misses a regulating control as frequently found in natural systems. In this regard light can be considered as an almost ideal trigger, because of its non-invasive interaction with matter, but also because of the disitinct advantage to provide very good temporal and spatial resolution. As first proof of principle we want to modify the activity and control the selectivity of organocatalysts in situ by the use of light.

Keywords: homogeneous catalysis,organic chemistry,organocatalysis,regulation,proline,photolabile protecting groups,photoswitchs
The speed of molecular evolution: rate shifts, gene function and natural selection in primate history (PRIMATE HETEROTACHY)

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-IEF-2008, 2008)
Start date: 2009-11-01
End date: 2011-10-31
Duration (months): 24.0
Total project cost (EUR): 162568.66
EU funding (EUR): 162568.66
Participants: 1
Project status: CLOSED

Which genes have shifted in evolutionary rates during the history of the Primates (monkeys, apes and humans); and what does the function of these genes tell us about adaptation in our Order? The aim of this proposal is to investigate changes in the speed of primate gene evolution, using complete genome sequences from at least six species of Primates augmented by data from other species in the Order, including Neanderthals. The specific aims of the proposal are i) to identify functional classes of genes (e.g. cognition and immune system) whose rates of evolution diverge from general trends in primate gene evolution, ii) to build a picture of the gene functions that characterise human evolution integrated over the 20,000 to 25,000 human genes, and iii) to relate these functional classes to selective processes at the level of primate ecology (e.g. parasitism, predation, mating system and social behaviour). The work will require novel bioinformatics and comparative methods that can identify genes whose evolution varies in rate and mode throughout the primate tree, and these be developed and made freely available to other scientists. By building on a wider set of species and genes than previously studied the results of the research will provide the first “whole genome functional map” perspective of the conserved and altered gene functions occurring during the evolution of the lineage leading to modern humans.

Keywords: phylogeny,genomics,proteomics,bioinformatics,computational biology,molecular evolution,human biology,heterotachy,comparative analysis
Application of directed evolution to the study of structural enzyme dynamics (KE07-LDH)

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: France
Call:  (FP7-PEOPLE-IIF-2008, 2008)
Start date: 2009-06-01
End date: 2011-05-31
Duration (months): 24.0
Total project cost (EUR): 167145.57
EU funding (EUR): 167145.57
Participants: 1
Project status: CLOSED

We propose to study the importance of structural dynamics to enzymatic catalysis. This will utilise simplified model systems in which a variety of catalytically distinct mutants have been generated though directed evolution. This research will focus on whether changes to the conformational landscape of enzymes affect catalysis and how the structural scaffold can determine the optimum temperature for enzymatic activity. Two model systems will be used: (i) the lactate dehydrogenase family, chosen because it is the most heavily studied family with regards to thermophilicity; (ii) a designed Kemp elimination catalyst, chosen because it is the first example of an enzyme in which the evolution of the active site and structural scaffold has been decoupled. A synergistic experimental approach will be used to study the mutants generated through directed evolution: - Biophysics (temperature-controlled cryo-crystallography, incoherent neutron scattering, in-cristallo spectroscopy) and detailed data analysis (anisotropic and multiple crystallographic refinement) - Enzyme kinetics (temperature dependent kinetics and Arrhenius plots) - Computational simulation (normal mode analysis and molecular dynamics) This project will constitute, to our knowledge, one of the first attempts to apply directed evolution to the systematic analysis of the importance and evolution of pathways for dynamic conformational change in enzymatic catalysis.

Keywords: molecular biophysics,computational chemistry,enzimology,biological engineering,radiation physics