Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Species formation from beginning to end: integrative tests of competing hypotheses for the origins of diversity (NATHISGEN)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Evolutionary, population and environmental biology
Countries involved: United Kingdom
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-11-01
End date: 2016-10-31
Duration (months): 60.0
Total project cost (EUR): 1882858.0
EU funding (EUR): 1882858.0
Participants: 1
Project status: CLOSED

Biological diversity is created by the formation of new species and thus speciation is a fundamental process responsible for diversity of life. Progress has been made in identifying individual ‘speciation genes’ causing specific forms of reproductive isolation. In contrast, debates persist about how the speciation process unfolds from beginning to end (i.e., the mechanisms of speciation) and the fraction of the genome involved. What factors explain variability in how far speciation proceeds? This question was framed by Darwin and an active debate concerns whether speciation proceeds further via: (1) strong natural selection on a few genes, resulting in isolated ‘genomic islands of divergence’, or (2) by selection acting on a greater number of genes across the genome. This proposal outlines a research program aimed at resolving this debate, a task that is required to understand the origins of diversity. Specifically, I will use field experiments which measure natural selection at the genomic level to directly test, for the first time, how selection acts on the genome across different stages of the speciation process. The approach uses an integrative combination of eco-morphology, next-generation DNA sequencing, population genomics, manipulative experiments in nature, and linkage mapping to study the origins of diversity. The work is novel in: (1) examining many closely-related taxon pairs (rather than just a few) which vary in how far speciation has proceeded, thereby reconstructing how speciation unfolds, and (2) experimentally measuring (rather than inferring via observation) selection on the genome. The proposed work will clarify our understanding of speciation. By coupling genomics and ecology via experimental approaches, the results will build a new understanding of the natural history of the genome.

Keywords: adaptation,biodiversity,insect-plant interaction,natural selection,population genomics,speciation
Synthesis of mono-dithiolene molybdenum complexes and their evaluation as potential drugs for the treatment of human isolated sulfite oxidase deficiency. (MOCOMODELS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Applied life sciences and biotechnology
Countries involved: Germany,Ireland
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-02-01
End date: 2018-01-31
Duration (months): 72.0
Total project cost (EUR): 1499870.0
EU funding (EUR): 1499870.0
Participants: 3
Project status: CLOSED

Two rare but usually fatal diseases are caused by a failure at different levels of the multistep biosynthetic generation of the three human molybdenum dependent enzymes involved in metabolic processes. In contrast to the more general Moco deficiency (MocoD) affecting all three enzymes, isolated sulfite oxidase deficiency (iSOD) cannot be treated yet. The proposed project is primarily aimed at synthesising a large variety of molybdenum complexes that mimic the natural molybdenum cofactor of the respective enzymes. These compounds will be prepared with a focus on distinct aspects of the biomolecules (first coordination sphere, different functional groups of the complex molybdopterin ligand, hydrogen bonding sites); their stability and ability to catalyse oxygen atom transfer (in particular the oxidation of sulfite) will be assessed and their suitability to bind in the active site pocket of the protein and restore activity will be tested. In addition alternative metals will be investigated with respect to possible benefits regarding stability and activity. The ultimate aim is to combine all the different synthetic approaches and information about properties to build a compound containing all indispensable functional groups while being stable, active and made with the least possible effort. Consequently this project addresses the human iSOD by developing synthetic structural models for the molybdenum cofactor active site of sulfite oxidase, testing their potential for incorporation into the biotechnologically generated apo-enzyme and evaluating the activity of the resulting semi-synthetic enzymes thereby assessing their suitability as future iSOD treatments. This work will have impact on the way iSOD and MocoD patients will be treated in the future and deepen the understanding of fundamentally important chemical, structural and catalytic aspects of the Moco dependent enzymes.

Keywords: bioinorganic chemistry,cofactor synthesis,molybdenum,oxo transfer catalysis
Induction of Insulin-producing beta-cells Regeneration in vivo (BETAREGENERATION)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: France
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2016-12-31
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Diabetes has become one of the most widespread metabolic disorders with epidemic dimensions affecting almost 6% of the world’s population. Despite modern treatments, the life expectancy of patients with Type 1 diabetes remains reduced as compared to healthy subjects. There is therefore a need for alternative therapies. Towards this aim, using the mouse, we recently demonstrated that the in vivo forced expression of a single factor in pancreatic alpha-cells is sufficient to induce a continuous regeneration of alpha-cells and their subsequent conversion into beta-like cells, such converted cells being capable of reversing the consequences of chemically-induced diabetes in vivo (Collombat et al. Cell, 2009). The PI and his team therefore propose to further decipher the mechanisms involved in this alpha-cell-mediated beta-cell regeneration process and determine whether this approach may be applied to adult animals and whether it would efficiently reverse Type 1 diabetes. Furthermore, a major effort will be made to verify whether our findings could be translated to human. Specifically, we will use a tri-partite approach to address the following issues: (1) Can the in vivo alpha-cell-mediated beta-cell regeneration be induced in adults mice? What would be the genetic determinants involved? (2) Can alpha-cell-mediated beta-cell regeneration reverse diabetes in the NOD Type 1 diabetes mouse model? (3) Can adult human alpha-cells be converted into beta-like cells? Together, these ambitious objectives will most certainly allow us to gain new insight into the mechanisms defining the identity and the reprogramming capabilities of mouse and human endocrine cells and may thereby open new avenues for the treatment of diabetes. Similarly, the determination of the molecular triggers implicated in the beta-cell regeneration observed in our diabetic mice may lead to exciting new findings, including the identification of “drugable” targets of importance for human diabetic patients.

Keywords: reprogramming,regeneration,type 1 diabetes
Stress signaling mechanisms in metabolism and inflammation and related disorders (STRESSMETABOL)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: France
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-02-01
End date: 2017-01-31
Duration (months): 60.0
Total project cost (EUR): 1499360.0
EU funding (EUR): 1499360.0
Participants: 1
Project status: CLOSED

Protein kinases represent key signal transduction components transferring signals to their effectors by phosphorylation. Among other important functions, MAPK-dependent signal transduction is principally required to control inflammation and metabolism in vertebrates. However, chronic MAPK signaling in response to environmental stress contributes to the development of metabolic and inflammatory diseases. While most studies investigated functions of p38α of the p38 MAPK family, we have recently identified first non-redundant in vivo functions for p38δ. We found that p38δ regulates glucose homeostasis by controlling insulin secretion from pancreatic β cells and more recently that p38δ is pivotal in regulation of neutrophil-mediated inflammation. At the molecular level, both functions are dependent on Protein Kinase D1 (PKD1) activity, the latter of which, we identified as a direct and negatively regulated target of p38δ. Overall, our recent work describes a new signaling axis that may be important in diabetes mellitus and inflammatory diseases, respectively. The future core activity of my laboratory is directed towards elucidation of particular roles of p38δ and PKD1 downstream targets in neutrophils and β cells. We also aim at finding common upstream signaling mechanisms that converge in p38δ-PKD1 signaling. Finally, we will explore newly discovered potential metabolic processes that are regulated by this signaling module. This biased research will be complemented by a more comprehensive proteomic screening approach in liver focusing on basic metabolic adaption in response to fasting and feeding. While, protein phosphorylation is widely explored in this context, we will globally screen for ubiquitination of proteins that recently emerged as a key event in cellular signaling. Our work will hopefully lead to the discovery of novel and important cellular and molecular mechanisms in metabolism and inflammation with relevant implications in related human disorders.

Keywords: diabetes,obesity,inflammation,fatty liver disease,insulin resistance,insulin secretion,beta cell,neutrophil,mapk,pkd,jnk,p38
Endothelial homeostasis and dysfunction in metabolic-vascular retina disease: The role of endothelial cell-intrinsic and endothelial cell extrinsic inflammatory pathways (ENDHOMRET)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: Germany
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-11-01
End date: 2016-12-31
Duration (months): 62.0
Total project cost (EUR): 1488480.0
EU funding (EUR): 1488480.0
Participants: 1
Project status: CLOSED

Diabetic retinopathy (DR) is a major cause of blindness in adults and the underlying pathophysiology includes endothelial dysfunction. Endothelial dysfunction is a perturbation of endothelial homeostasis including changes in endothelial barrier integrity, alterations of the endothelial cell surface, which becomes proinflammatory and mediates increased leukocyte adhesion and changes in endothelial survival functions. Endothelial dysfunction is regulated by an intimate crosstalk of the endothelium with leukocytes and inflammatory pathways of the innate immunity (endothelial-extrinsic pathways), which are activated in the diabetic vasculature affecting the endothelial barrier and leukocyte adhesiveness, and by endothelial cell-intrinsic pathways affecting endothelial survival that are regulated by specific components of the diabetic microenvironement, e.g. hypoxia. The aims of the present proposal are (i) to assess how leukocyte-endothelial interactions (here a particular emphasis will be laid on novel components of the leukocyte adhesion cascade, such as Developmental endothelial locus-1 or Junctional Adhesion Molecule-C, recently identified by the group of the applicant), as well as how macrophage activation/polarization in the local retinal microenvironment affect endothelial homeostasis and dysfunction in the course of DR, and (ii) to investigate pathways regulating survival functions of the endothelium particularly under hypoxic/ischemic conditions in the diabetic retina. The proposal is highly innovative, since the knowledge about these pathways in the context of endothelial dysfunction in DR is scarce. Understanding the molecular contribution of endothelial cell-extrinsic inflammatory pathways and endothelial-cell intrinsic, survival-regulating pathways in the context of DR will have a high impact as it will provide the platform for developing novel specific therapeutic approaches for this major diabetic complication.

Keywords: inflammation,endothelial biology,diabetic retinopathy,neovascularisation,leukocyte-endothelial interactions,endothelial homeostasis,endothelial survival,macrophages
Thylakoid membrane in action: acclimation strategies in algae and plants (ASAP)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: Netherlands
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-12-01
End date: 2017-11-30
Duration (months): 72.0
Total project cost (EUR): 1696961.0
EU funding (EUR): 1696961.0
Participants: 2
Project status: CLOSED

Life on earth is sustained by the process that converts sunlight energy into chemical energy: photosynthesis. This process is operating near the boundary between life and death: if the absorbed energy exceeds the capacity of the metabolic reactions, it can result in photo-oxidation events that can cause the death of the organism. Over-excitation is happening quite often: oxygenic organisms are exposed to (drastic) changes in environmental conditions (light intensity, light quality and temperature), which influence the physical (light-harvesting) and chemical (enzymatic reactions) parts of the photosynthetic process to a different extent, leading to severe imbalances. However, daily experience tells us that plants are able to deal with most of these situations, surviving and happily growing. How do they manage? The photosynthetic membrane is highly flexible and it is able to change its supramolecular organization and composition and even the function of some of its components on a time scale as fast as a few seconds, thereby regulating the light-harvesting capacity. However, the structural/functional changes in the membrane are far from being fully characterized and the molecular mechanisms of their regulation are far from being understood. This is due to the fact that all these mechanisms require the simultaneous presence of various factors and thus the system should be analyzed at a high level of complexity; however, to obtain molecular details of a very complex system as the thylakoid membrane in action has not been possible so far. Over the last years we have developed and optimized a range of methods that now allow us to take up this challenge. This involves a high level of integration of biological and physical approaches, ranging from plant transformation and in vivo knock out of individual pigments to ultrafast-spectroscopy in a mix that is rather unique for my laboratory and will allow us to unravel the photoprotective mechanisms in algae and plants.

Keywords: photosynthesis,photobiology
Defining a Roadmap for Cooperative Health research between the EU and Latin America-Caribbean countries: a Policy Oriented Approach (EU-LAC HEALTH)

Framework: FP7 — Cooperation
Programme: Health
Destination: Other Actions across the Health Theme
Action type: Coordination and support actions
Countries involved: Spain,Costa Rica,Switzerland,Germany,Brazil,Argentina,Italy,France,Mexico
Call:  (FP7-HEALTH-2011-single-stage, 2011)
Start date: 2011-10-01
End date: 2017-06-30
Duration (months): 69.0
Total project cost (EUR): 2256420.75
EU funding (EUR): 1992715.0
Participants: 10
Project status: CLOSED

The EU-LAC Health coordinating action proposes to define a detailed plan to guide policy makers and other stakeholders on future actions to support cooperative Health Research between Latin America and Caribbean countries (LAC) and the European Commission and Member States (EU). This consensus Roadmap will be developed using a policy oriented approach and taking into account the new political framework for EU-LAC collaboration in S&T. The Roadmap will provide policy-makers and R&D funding bodies with new insights on how to best coordinate and fund cooperative health research between the two regions. An important effort will be devoted during the project to link and coordinate two important policy areas with strong involvement in health research funding: Science and technology policy (research) and International development cooperation. EU-LAC Health will have as main goals to: a) Discuss and explore, with policy-makers and other stakeholders, how to best coordinate health research policies and funding between EU and LAC. b) Establish a consensus Roadmap for cooperative health research with the final objective of setting up a future framework for collaboration between the EU and LAC regions in this field. c) Disseminate the project results to the main project stakeholders as a means to increase and improve EU-LAC cooperation in health research. The project is planned as a 5 year Support Action, carried out by a consortium of 8 participants from Spain, Switzerland/Mexico, Argentina, Costa Rica, Brazil, Italy and Germany. The selected institutions form a multidisciplinary team with participants from Health Research policy-making Institutions, R&D Funding Agencies, Research Centers, and specialized R&D consulting companies. The project will benefit from a direct participation of main stakeholders from policy making and funding institutions involved in EU LAC health research, as members of the advisory board and a high level expert group.

Keywords: s&t cooperation health research eu-latin america caribbean policy making r&d funding bodies developmental aid
Memory-Related Information Processing in Neuronal Circuits of the Hippocampus and Entorhinal Cortex (HIPECMEM)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: Austria
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-11-01
End date: 2016-10-31
Duration (months): 60.0
Total project cost (EUR): 1441119.0
EU funding (EUR): 1441119.0
Participants: 1
Project status: CLOSED

This proposal will elucidate the circuit mechanism that underlies the spatial memory-related information processing in the interconnected brain areas of the hippocampus and entorhinal cortex (EC). Both of these areas are implicated in spatial memory and encode spatial information in neuronal activity patterns. The mechanisms underlying the emergence and coordination of spatial memory-related activity in these regions are needed to understand how these circuits process mnemonic information. Accordingly, here we aim at elucidating the representation of spatial memory by investigating these mechanisms at the circuit and synaptic levels of organisation. The first objective of this proposal is to characterise oscillatory synchronisation in hippocampo-EC circuits at different stages of memory processing. We hypothesise that network oscillations facilitate circuit interactions during memory processing. Therefore, using optogenetic techniques to disrupt oscillations, we aim at identifying critical periods during mnemonic processing when synchronisation is needed. Secondly, we intend to reveal how mnemonic information is encoded and exchanged between different areas of the hippocampo-EC system. We will test whether spatial memory-associated firing of dorsal hippocampal cells could be triggered by EC and/or ventral hippocampal cells that encode similar mnemonic features. In addition, this project will explore the role of temporal coding in the representation and consolidation of spatial memory traces. The third objective will investigate synaptic changes between connected CA3-CA3 and CA3-CA1 cell pairs during spatial learning. We will use cross-correlation analysis and electrical microstimulation to examine the rules that govern changes in synaptic efficacy by observing the probability of spike transmission. Overall, the proposal provides a comprehensive approach to understanding how hippocampo-EC circuits organise and store information during mnemonic processes.

Keywords: oscillations,temporal coding,spatial memory,cell assembly,multi-channel recordings,synchronization,sharp waves,memory consolidation
Environmental Effects and Risk Evaluation of Engineered Nanoparticles (ENVNANO)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Applied life sciences and biotechnology
Countries involved: Denmark
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-12-01
End date: 2016-03-31
Duration (months): 52.0
Total project cost (EUR): 1196260.0
EU funding (EUR): 1196260.0
Participants: 1
Project status: CLOSED

The objective of the project Environmental Effects and Risk Evaluation of Engineered Nanoparticles (EnvNano) is to elucidate the particle specific properties that govern the ecotoxicological effects of engineered nanoparticles and in this way shift the paradigm for environmental risk assessment of nanomaterials. While current activities in the emerging field of nano-ecotoxicology and environmental risk assessment of nanomaterials are based on the assumption that the methodologies developed for chemicals can be adapted to be applicable for nanomaterials, EnvNano has a completely different starting point: The behaviour of nanoparticles in suspension is fundamentally different from that of chemicals in on solution. Therefore, all modifications of existing techniques that do not take this fact into account are bound to have a limited sphere of application or in the worst case to be invalid. By replacing the assumption of dissolved chemicals with a particle behaviour assumption, the traditional risk assessment paradigm will be so seriously impaired that a shift of paradigm will be needed. EnvNano is based on the following hypotheses: 1. The ecotoxicity and bioaccumulation of engineered nanoparticles will be a function of specific physical and chemical characteristics of the nanoparticles; 2. The environmental hazards of engineered nanoparticles cannot be derived from hazard identifications of the material in other forms; 3. Existing regulatory risk assessment procedures for chemicals will not be appropriate to assess the behaviour and potential harmful effects of engineered nanoparticles on the environment. These research hypotheses will be addressed in the four interacting research topics of EnvNano: Particle Characterization, Ecotoxicty, Bioaccumulation, and Framework for Risk Evaluation of Nanoparticles aimed to form the foundation for a movement from coefficient-based to kinetic-based environmental nanotoxicology and risk assessment.

Keywords: nanotechnology,risk assessment,ecotoxicology,nanoparticles