Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Towards Understanding the Structure and Dynamics of Receptor Proteins (TUDOR)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: Germany
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-04-01
End date: 2015-03-31
Duration (months): 60.0
Total project cost (EUR): 2449840.0
EU funding (EUR): 2449840.0
Participants: 1
Project status: CLOSED

Upon binding an agonist, the seven transmembrane (TM) helical bundle of a G-protein coupled receptor (GPCR) undergoes conformational changes that catalyze nucleotide exchange within bound G proteins. In rhodopsin, the agonist arises from light-induced isomerization of the retinal ligand, but an active conformation (Ops*) can also be adopted by the opsin apoprotein. We recently solved the structure of Ops* in complex with a peptide from the C-terminal ±-5 helix of the G protein. Considering this structure and previous work, we postulate a mechanism by which the 40 Å gap between the retinal and the nucleotide binding site is bridged. First, TM5 and TM6 engage in new interactions to form a mitt-like structure into which the G-protein ±-5 helix can bind. Second, the bound ±-5 helix switches into a new position, thereby acting as a transmission rod to the nucleotide binding site. In the proposed project, we will test this mechanism and explore the underlying protein dynamics by: - determining the structure of the receptor in complex with longer peptides, and if possible, with the G holoprotein, - measuring conformational changes on the timescale of receptor activation (ms) and expand computational modelling of the respective transitory complexes, - determining the underlying backbone dynamics and fluctuations on the ps-ns time scale by experimentation and molecular dynamics. Some of the necessary methodologies are available, while others must be developed or made available through collaborations. Rhodopsin is the ideal model system for studying signal transduction mechanisms. Our novel multi-prong approach, while risky, will enormously improve our understanding of GPCR signalling mechanisms. The insights gained will be significant for receptor-directed drug development.

Keywords: infrared spectroscopy,electron paramagnetic resonance,single molecule fluorescence,computational modeling,g-protein coupled receptor
Linking GABAergic neurones to hippocampal-entorhinal system functions (GABACELLSANDMEMORY)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: Germany
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-07-01
End date: 2015-06-30
Duration (months): 60.0
Total project cost (EUR): 1872000.0
EU funding (EUR): 1872000.0
Participants: 1
Project status: CLOSED

GABAergic interneurones can effectively synchronize the activity of principal cells giving rise to distinct oscillatory patterns. A particular rhythm, hippocampal theta oscillations (6-10Hz), links two ways of coding by which pyramidal cells in the hippocampus represent space, namely rate and phase coding. Thus, the theta cycle provides a clock against which the increased firing rate of pyramidal cells in the hippocampus and entorhinal cortex is measured. Furthermore, hippocampal theta is believed to constitute a link to episodic memory. Recent evidence from our lab indicates that recruitment of GABAergic interneurones critically affects certain aspects of hippocampus-dependent spatial memory in mice. We have established genetic tools that allow us to manipulate GABAergic interneurones in a cell type and region-specific manner. In combination with in vivo electrophysiology in the hippocampus/entorhinal cortex and behavioural studies, we will investigate how GABAergic interneurones regulate the activity in neuronal networks and contribute to behaviour. Specifically, we will address the following questions: 1) How does reduced recruitment of GABAergic interneurones affect network activity (theta oscillations)? 2) How does altered activity of GABAergic interneurones affect spatial representation (activity of place cells in the hippocampus and grid cells in the entorhinal cortex)? 3) How does modified activity in the hippocampus affect activity in the entorhinal cortex (and vice versa)? 4) How does modified network activity and spatial representation translate into spatial memory? The interdisciplinary approach will enable us to provide better insight into how cellular activity of GABAergic interneurones relates to network activity and ultimately to behaviour.

Keywords: inhibition,mouse genetics,grid/place cells,oscillations,spatial memory.
Wild Evolutionary Genomics (WEG)

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: United Kingdom
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-09-01
End date: 2016-08-31
Duration (months): 72.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 1
Project status: CLOSED

150 years since the Origin of Species, we do not know how natural selection acts at the level of the genome in natural populations in ecological time, but elucidation is within reach. This study will investigate natural selection, and the genome's response to it, in unprecedented detail by combining two resources. The Soay sheep population on the island of Hirta, St. Kilda, Scotland is one of the most thoroughly phenotyped wild animal populations in the world and already the subject of internationally famous interdisciplinary research. The recently developed International Sheep Genomics Consortium 60K chip identifies 38,777 single nucleotide polymorphisms in Soay sheep. We will genotype 5,000 Soays for these SNPs. We will first analyse the data to test the effect of realised relatedness and inbreeding coefficients on trait heritabilities, genetic correlations and inbreeding depression. We predict that all estimates will increase, generating much increased power for more complex studies. Second, we will identify genome regions harbouring quantitative trait loci (QTL) and inbreeding depression and genotype additional sheep at SNPs in haplotypes predicting this variation. We will subject these regions to intensive analyses to understand their genetic effects, the action of selection on them and their response to selection. Finally, we will count the recombination events in each parent during the creation of each offspring and conduct a comprehensive analysis of sources of individual variation in recombination, the first of its kind in a wild population.

Keywords: evolution,natural selection,qtl
Dorsal Horn Interneurons in Sensory Processing (DHISP)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: Switzerland
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-05-01
End date: 2016-04-30
Duration (months): 72.0
Total project cost (EUR): 2467000.0
EU funding (EUR): 2467000.0
Participants: 1
Project status: CLOSED

Chronic pain syndromes are to a large extent due to maladaptive plastic changes in the CNS. A CNS area particularly relevant for such changes is the spinal dorsal horn, where inputs from nociceptive and non-nociceptive fibers undergo their first synaptic integration. This area harbors a sophisticated network of interneurons, which function as a gate-control unit for incoming sensory signals. Several different types of interneurons can be distinguished based e.g. on their neurotransmitter and neuropeptide content. Despite more than 40 years of research, our knowledge about the integration of these neurons in dorsal horn circuits and their contribution to sensory processing is still very limited. This proposal aims at a comprehensive characterization of the dorsal horn neuronal network under normal conditions and in chronic pain states with a focus on inhibitory interneurons. A genome-wide analysis of the gene expression profile shall be made from defined dorsal horn interneurons genetically tagged with fluorescent markers and isolated by fluorescence activated cell sorting. A functional characterization of the connectivity of these neurons in spinal cord slices and of their role in in vivo sensory processing shall be achieved with optogenetic tools (channelrhodopsin-2), which permit activation of these neurons with light. Finally, behavioral analyses shall be made in mice after diphteria toxin-mediated ablation of defined interneuron types. All three approaches shall be applied to naïve mice and to mice with inflammatory or neuropathic pain. The results from these studies will improve our understanding of the malfunctioning of sensory processing in chronic pain states and will provide the basis for novel approaches to the prevention or reversal of chronic pain states.

Keywords: spinal cord,interneurons,electrophysiology,transgenic mice
Genes, environment and immunity in the pathogenesis of rheumatoid arthritis (PREVENTRA)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: Sweden
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-04-01
End date: 2016-03-31
Duration (months): 72.0
Total project cost (EUR): 2000000.0
EU funding (EUR): 2000000.0
Participants: 1
Project status: CLOSED

Aims and significance: The aims of this program are (1) To obtain new understanding of how environmental and life style factors interact with genes to induce immune reactions able to cause the different forms of arthritis that are defined as RA; (2) To use this understanding to develop prevention and targeted therapy for different forms of RA, and to enable efficient and eventually curative therapy. Background: We build on new understanding or RA etiology that has followed from studies on interactions between genes, environment and immunity in different subsets of RA. This has been provided for new detailed studies on specific and eventually disease-inducing autoimmunity in RA. Research program: We will use our infrastructure (longitudinal large cohorts, biobanks genetic information and our molecular immunology laboratory) to investigate (1) how genes and environment interact in causing different forms of RA; (2) how specific immune reactions against post-translationally modified (mainly citrullinated) autoantigens are triggered by environmental agents in specific genetic contexts in different individuals; (3) How these immune reactions target different organs (joints, lungs etc) and eventually cause arthritis in model systems; (4) how the combination of genes, environment and immunity may determine disease course and response to various therapies. Novelty and opportunities to take knowledge of autoimmune disease and RA to a new level: The recent advances in understanding interactions between genes, environment and immunity in RA, provides a striking new opportunity to understand basic features of autoimmunity and autoimmune disease, as well as potentials to prevent and treat RA very early. I believe that the presented program is well positioned to use this opportunity and contribute to a new paradigm for understanding and preventing RA.

Keywords: diagnosis,immunotherapy,public health
Linear ubiquitin chains - novel cellular signals involved in inflammation and cancer (LINEUB)

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: Germany
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-06-01
End date: 2015-05-31
Duration (months): 60.0
Total project cost (EUR): 2440560.0
EU funding (EUR): 2440560.0
Participants: 1
Project status: CLOSED

Ubiquitin (Ub) is a small modifier that labels proteins in a highly specific manner. Like phosphorylation, modification of proteins by Ub is prevalent in the majority of cellular processes. An increasing number of distinct functions have been assigned to different types of ubiquitin modifications (monoUb and different Lys-linked chains). Moreover, aberrations in the ubiquitin system underlie many disease states, including cancer, inflammatory, immune and metabolic disorders as well as neurodegeneration. The most recently described physiological ubiquitin modification is the linear ubiquitin chain, in which ubiquitin monomers are conjugated via Met-Gly linkages. We have found that linear ubiquitin chains bind specifically to the NEMO adaptor molecule, an event critical for the proper regulation of NF-ºB signaling (Rahighi, 2009). Here we propose to use a multidisciplinary strategy to study the role of linear ubiquitination in the NF-ºB pathway, autophagy, apoptosis and DNA repair and how these changes can impact on disease states such as inflammation and cancer development. Scientific objectives are: &quot; Characterize the components of linear ubiquitination: E3 ligases, specific substrates and domains recognizing linear ubiquitin chains &quot; Elucidate the in vivo role of linear ubiquitination in the regulation of the NF-ºB pathway, apoptosis and DNA repair. &quot; Reveal the molecular basis for the connections between linear ubiquitination and selective autophagy &quot; Identify elements in the linear ubiquitin network as potential drug targets &quot; Generate transgenic mouse models of inflammatory diseases and cancer &quot; Develop system and computational biology approaches to assess the global role of linear ubiquitination in cellular proteome

Keywords: ubiquitin,linear chains,ubiquitin binding domains,autophagy,inflammation,cancer
Pre-receptor cortisol metabolism and human ageing (PRECORT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: United Kingdom,United Kingdom
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-05-01
End date: 2016-04-30
Duration (months): 72.0
Total project cost (EUR): 2499760.4
EU funding (EUR): 2499760.4
Participants: 2
Project status: CLOSED

The number of people over the age of 80 years in the 25 EU member states is currently 18.2 million or 4% of the total population; by 2020, 20% of the EU population will be &gt;65 years old which will place considerable burden upon limited health care resources. 70% of older adults report at least one chronic disease that contributes to a reduction in healthspan or the number of extra years spent in good health. The European Commission is committed to identify rational and evidence based approaches to improve health in old age and as such has identified Ageing research as a priority. The most prevalent conditions that contribute to the ageing phenotype are sarcopaenia, hypertension and cardiovascular disease, central adiposity and type 2 diabetes mellitus and osteoporosis. Here there are remarkable similarities to patients with Cushing s syndrome caused by excessive secretion of glucocortiocoids such as cortisol. PRECORT Prereceptor Cortisol metabolism and human Ageing will test the hypothesis that age-related changes in body composition (central adiposity, reduced bone and muscle mass, skin thinning) and resulting chronic disease (diabetes, osteoporosis, sarcopaenia, hypertension, cardiovascular disease) are caused by excessive glucocorticoids as a result of age-related activation of the pituitary-adrenal axis and/or increased 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1), an enzyme that can generate cortisol locally within fat, bone, muscle and skin. The proposal will complete the full cycle of translational research and will potentially offer a new therapeutic approach through selective 11b-HSD1 inhibitors to modulate the ageing phenotype thereby improving the healthspan of the Ageing EU community.

Keywords: ageing,endocrinology,glucocorticoids,cortisol,hydroxysteroid dehydrogenase,metabolism
Monoallelic Gene Expression in Malaria Parasites: A Key Mechanisms in the Pathogen's Survival Strategy (PLASMOESCAPE)

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: France
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-06-01
End date: 2015-05-31
Duration (months): 60.0
Total project cost (EUR): 1815480.0
EU funding (EUR): 1815480.0
Participants: 1
Project status: CLOSED

An important number of human and animal pathogens use antigenic variation of surface proteins as a mechanism to avoid destruction by the host s immune system. Most escape mechanisms rely on the successive expression of members of gene families in a mutually exclusive manner, a biological process which remains elusive at the molecular level. The protozoan pathogen Plasmodium falciparum, which infects up to 300 million people causing more than two million lives each year, undergoes antigenic variation to establish chronic blood stage infection. A critical determinant in chronic infection and pathogenesis is the expression of clonally variant molecules at the surface of infected erythrocytes. Several variant gene families undergo antigenic variation in P. falciparum and are expressed during blood stage infection. One family encoded by 60 var genes expresses the most well-known virulence factor causing severe malaria (capillary blockages in the brain and other organs mediated by infected erythrocytes). Switching expression between the 60-member var gene family avoids immune clearance and prolongs the period of infection and transmission to the mosquito. The initial event controlling mono allelic expression at a unique expression site remains elusive and represents the Holly Graal in the field of phenotypic variation. To this end, the major objective of this proposal is to identify specific factors contributing to active expression sites (proteins, DNA enhancer or ncRNA) by using novel strategies such as Proteomics of Isolated Chromatin segments (PICh) and Chromosome Conformation Capture (3C). We expect that new insights into the underlying principles of gene counting of virulence gene families may reveal an Achilles Heel of the parasite s immune evasion strategy.

Keywords: perinuclear expression site,nuclear architecture,telomere repression
Exploring Morphospaces in Adaptive Radiations to unravel Ecological Speciation (EMARES)

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: United Kingdom,Netherlands
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-10-01
End date: 2016-06-30
Duration (months): 69.0
Total project cost (EUR): 2474128.0
EU funding (EUR): 2474128.0
Participants: 2
Project status: CLOSED

150 years from the Origin and we have yet to unravel how ecological speciation works, and how it leads to spectacular adaptive radiations. The process has two components: adaptation to ecological niches and production of new species. My aim is to make breakthroughs in understanding ecological speciation by the study of geographically parallel adaptive radiations in mycalesine butterflies that have yielded some 250 extant species in the Old World tropics. More empirical studies are needed because few radiations have been examined from many different perspectives (including in insects). It is not fully understood either how exactly radiation occurs or how exactly selection leads to speciation. This proposal provides a unique opportunity, outside a few vertebrate clades, to resolve this by fully integrating several lines of evidence and methodologies. My approach will be to study patterns of diversity and disparity in morphospace for several sets of key traits: 1) wing patterns, 2) larval host plant choice especially with respect to C3 and C4 photosynthesis, and 3) male secondary sexual traits and sex pheromones. We will collect phenotypic, genetic, developmental, and ecological data. Application of phylogenetic comparative methods to the relationships of all traits among all species will make inferences about the biological mechanisms that have driven diversification and speciation. The combination of surveys of morphospace, the use of comparative methods, and microevolutionary studies using laboratory models will provide a unique comprehensive view. Our analyses will distinguish among alternative patterns of adaptive radiations, test predictions from models, and move us forward in identifying the drivers of observed patterns.

Keywords: evo-devo,genomics,speciation,adaptive radiation
Take-up activities by universities of specific guidelines and recommendations to implement their modernisation agenda (EUIMA)

Framework: FP7 — Capacities
Programme: Science in Society
Destination: Science in Society
Action type: Coordination and support actions
Countries involved: Belgium
Call:  (FP7-Adhoc-2007-13, 2007)
Start date: 2010-01-01
End date: 2012-06-30
Duration (months): 30.0
Total project cost (EUR): 1355235.2
EU funding (EUR): 1200000.0
Participants: 1
Project status: CLOSED

The project addresses two main elements of the modernisation agenda for Europe’s universities (i) the sustainability of university funding, financial management and development of full-costing and (ii) the transparency and appropriateness of measurement tools for the assessment of university-based research reflecting the diversity of university missions. A third “transversal” focus running through the project in addressing these two main issues will be to identify requirements for further development of human resources and management in universities to enhance the attractiveness of university careers. It deals directly with the aims of the work programme in providing support for mutual learning, exchange of experiences by universities of guidelines and recommendations from European Commission Expert Groups on the impact of external project-based funding on the financial management of universities, and the assessment of university-based research. The project will draw upon related empirical evidence from several projects conducted by the European University Association with its individual and collective membership and in partnership with other European associations representing the business communities, regional agencies and non-governmental bodies. As a European approach, the “take-up” activities will provide a crucial comparative framework in which to promote the modernisation of universities. The European Research Area requires a globally competitive European university sector as a main stakeholder that needs funding mechanisms which support its sustainability and research assessment indicators that respect the aims and objectives of chosen strategic missions and measures their excellence on these terms. Through a series of workshops and study visits held at different universities across Europe as a result of an open competition with transparent selection criteria, the expected impact of the project will be that lasting concrete results are achieved.

Keywords: european universities,take up activities,european research area,funding sustainability,full costing,research assessment