Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
The adaptive advantages, evolution and development of iridescence in leaves (BLUELEAF)

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-2010-StG_20091118, 2010)
Start date: 2011-01-01
End date: 2016-07-31
Duration (months): 67.0
Total project cost (EUR): 1118378.0
EU funding (EUR): 1118378.0
Participants: 1
Project status: CLOSED

Iridescence is a form of structural colour which changes hue according to the angle from which it is viewed. Blue iridescence caused by multilayers has been described on the leaves of taxonomically diverse species such as the lycophyte Selaginella uncinata and the angiosperm Begonia pavonina. While much is known about the role of leaf pigment colour, the adaptive role of leaf iridescence is unknown. Hypotheses have been put forward including 1) iridescence acts as disruptive camouflage against herbivores 2) it enhances light sensing and capture in low light conditions 3) it is a photoprotective mechanism to protect shade-adapted plants against high light levels. These hypotheses are not mutually exclusive: each function may be of varying importance in different environments. To understand any one function, we need a interdisciplinary approach considering all three potential functions and their interactions. The objective of my research would be to test these hypotheses, using animal behavioural and plant physiological methods, to determine the functions of leaf iridescence and how the plant has adapted to the reflection of developmentally vital wavelengths. Use of molecular and bioinformatics methods will elucidate the genes that control the production of this potentially multifunctional optical phenomenon. This research will provide a pioneering study into the generation, developmental impact and adaptive significance of iridescence in leaves. It would also answer questions at the frontiers of several fields including those of plant evolution, insect vision, methods of camouflage, the generation and role of animal iridescence, and could also potentially inspire synthetic biomimetic applications.

Keywords: iridescence,animal vision and behaviour,optics,photoreceptors,shade adaptation
Reactive Oxygen Species in CTL-mediated Cell Death: from Mechanism to Applications (CTLANDROS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Immunity and infection
Countries involved: Switzerland
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-05-01
End date: 2016-04-30
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells release granzyme and perforin from cytotoxic granules into the immune synapse to induce apoptosis of target cells that are either virus-infected or cancerous. Granzyme A activates a caspase-independent apoptotic pathway and induces mitochondrial damage characterized by superoxide anion production and loss of the mitochondrial transmembrane potential, without disrupting the integrity of the mitochondrial outer membrane; while causing single-stranded DNA damage. GzmB induces both caspase-dependent and caspase-independent cell death. In the caspase-dependent pathway, mitochondrial functions are altered as evidenced by the loss of mitochondrial transmembrane potential and the generation of reactive oxygen species (ROS). The mitochondrial outer membrane (MOM) is disrupted, resulting in the release of apoptogenic factors. To date, research on mitochondrial-dependent apoptosis has focused on mitochondrial outer membrane permeabilization (MOMP) however whether the generation of ROS is incidental or essential to the execution of apoptosis remains unclear. Like human GzmA, human GzmB promotes cell death in a ROS-dependent manner. Preliminary data suggest that human GzmB can induce ROS in a MOMP-independent manner as Bax and Bak double knockout MEF cells treated with human GzmB and perforin still display a robust ROS production and dye in an ROS-dependent manner. Since GzmA and GzmB induce cell death in a ROS-dependent manner, we hypothesize that oxygen free radicals are central to the execution of programmed cell death induced by the cytotoxic granules. Therefore, the goal of this proposal is to dissect the key molecular events triggered by ROS that lead to Citotoxic Tcell-induced target cell death. A combination of biochemical, genetic and proteomic approaches in association with Electron Spin Resonance (ESR) spectroscopy methodology will be used to unravel the essential role ROS play in CTL-mediated killing.

Keywords: apoptosis,ctl,reactive oxygen species (ros),granzyme,perforin
Modeling congenital heart disease (CHD) in ISL1+ cardiovascular progenitors from patient-specific iPS cells (CHD-IPS)

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-2010-StG_20091118, 2010)
Start date: 2011-03-01
End date: 2017-02-28
Duration (months): 72.0
Total project cost (EUR): 1499996.25
EU funding (EUR): 1499996.25
Participants: 1
Project status: CLOSED

Tetralogy of Fallot (TOF) is the most common congenital heart disease (CHD) occurring 1 in 3000 births. Genetic studies have identified numerous genes that are responsible for inherited and sporadic forms of TOF, most of which encode key molecules that are part of regulatory networks controlling heart development. The identification of two populations of cardiac precursors, one exclusively forming the left ventricle and the second the outflow tract, the right ventricle and the atria, has suggested a new approach to interpret CHDs, in particular in TOF, not as a defect in a specific gene, but rather as a defect in the formation, expansion, and differentiation of defined subsets of embryonic cardiac precursors. The LIM-homeodomain transcription factor ISL1 marks the second population of cardiac progenitors, but little is known about its downstream targets, and how causative genes of CHDs affect cell-fate decisions in the ISL1 lineage. The main goals of this research program are: (1) to decipher the functional role of Isl1 downstream targets identified by a genome-wide ChIP-Seq approach; (2) to generate induced pluripotent stem (iPS) cells from controls and patients affected by severe forms of TOF characterized by defects in heart compartments known to derive from ISL1 cardiac progenitors; (3) to direct these iPS cells to ISL1+ cardiovascular precursors and identify cell-surface makers enabling their antibody-based purification; and (4) to use TOF-iPS-derived ISL1+ progenitors as an unique in vitro model system for deciphering molecular mechanisms that govern the fates and differentiation of this progenitor lineage and determine the pathological phenotype seen in TOF. This work will shed light on the molecular mechanisms of ISL1+ cardiac progenitor lineage specification and will give important new insights into the mechanisms of how alterations in transcriptional and epigenetic programs translate to a distinct structural defect during cardiogenesis.

Keywords: cardiac development,stem cell biology,ips cells
The European Network for Translational Research in Atrial Fibrillation (EUTRAF)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: United Kingdom,Netherlands,France,Germany,France,Germany,Germany,Switzerland,Austria,United Kingdom,United Kingdom,Germany,Germany,Germany,Germany,Germany,United Kingdom,Germany,Türkiye
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2010-11-01
End date: 2015-10-31
Duration (months): 60.0
Total project cost (EUR): 15681391.63
EU funding (EUR): 11997332.95
Participants: 20
Project status: CLOSED

The initiation and perpetuation of atrial fibrillation (AF) can be regarded as a complication of a progressive transformation of the structure and functional properties of the atria. This transformation is the result of complex and multiple changes at the molecular, cellular and organ levels which interact to form the basis for proarrhythmic mechanisms in AF. Numerous individual and environmental factors are probably involved in this profound transformation process in the atria. Therefore, we believe that progress in the diagnostics, prevention and treatment of AF requires highly integrative research from the molecule to bedside and from specific signaling pathways and electrophysiological mechanisms to population based studies. A consortium was formed providing this variety of expertises and has identified central research objectives for improvements in AF prevention and therapy. In 5 work packages focusing on basic research, new biomarkers for AF and therapeutic targets will be identified. We will study mechanisms of conduction disturbances in the atria, explore new ion channel targets for treatment of AF, identify specific alterations in the atria depending on the underlying heart disease, and evaluate beneficial effects of organ-protective compounds. Within two clinically oriented work packages the clinical application of these findings will be tested. The predictive value of diagnostic tools like serum biomarkers, 3D reconstruction of atrial conduction patterns based on high resolution body surface ECGs, and echocardiographic markers will be studied in large scale population studies. The new therapeutic targets will be explored in smaller prove-of-principle clinical trials (substrate oriented ablation, new pharmacological targets, and local gene delivery).

Keywords: atrial fibrillation - substrate
Dissection of molecular signature transformation during the process of pluripotency induction (ROADTOIPS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: United Kingdom
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-12-01
End date: 2015-11-30
Duration (months): 60.0
Total project cost (EUR): 1359000.0
EU funding (EUR): 1359000.0
Participants: 1
Project status: CLOSED

Induced pluripotent stem cells (iPSCs) are expected to have an enormous impact on medical research. However, the efficiency of reprogramming is still low and far from routine. Nevertheless, reprogramming with defined factors, Oct4, Sox2, Klf4 and c-Myc, is not a random event. Cells positive for SSEA-1, a marker of undifferentiated mouse ES cells (ESC), appear from cells which have lost the fibroblast marker Thy-1, prior to acquiring other pluripotent markers, e.g. Oct4, Nanog. Similarly, TRA-1-60 positive fully reprogrammed human iPSCs appear from SSEA-4 positive populations. Based on these observations, I hypothesize that there are essential ordered stages that the cells must undergo as they are directed toward pluripotency. To explore this hypothesis, I plan to perform three projects: 1. Identifying gene expression signatures during the successful reprogramming process. 2. Investigating serial changes of reprogramming factor binding, chromatin modifications and chromatin structure on the route to a pluripotent state. 3. Functional analysis of the candidate gene(s) identified for successful reprogramming. Based on my latest publication in Nature, I have developed an original highly efficient reprogramming system, in which almost all cells differentiated by retinoic acid treatment generate iPSCs by day 12 post reprogramming factor induction. The homogenous culture allowed by this system enables the unique execution of the objectives above, and for the first time will shed light on the molecular mechanisms of the reprogramming process. Accurate and more informed understanding of these ordered processes will allow derivation of strategies to improve the reprogramming technology.

Keywords: induction of pluripotency
The establishment and function of dorsiventral boundaries in plant organs (MHDVPATTERNING)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: Germany
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-01-01
End date: 2015-12-31
Duration (months): 60.0
Total project cost (EUR): 1498152.0
EU funding (EUR): 1498152.0
Participants: 1
Project status: CLOSED

The coordination of cellular behaviour that results in development involves the synchronization of many distinct patterning processes. A prime example of coordination at different levels is the process of lateral organ development. Firstly, a positioning system ensures that new organs initiate at the right locations. Secondly, gene expression must be patterned so as to define the different tissue types correctly. Lastly, specific patterns of localized growth must occur such that the organ develops to the correct size and morphology. How are these distinct processes regulated and what signals coordinate their patterning? By building on my recent work, this proposal aims, for the first time, to build an integrated understanding of how these distinct patterning processes arise and coordinate with one another, in the model plant species Arabidopsis thaliana. The proposal utilizes and extends the multispectral live-imaging techniques I pioneered as a postdoc and combines this approach with state-of-the-art transcriptomics and perturbation methods. Specifically, I aim to understand the regulatory links that coordinate dorsoventral patterning, cell polarity and morphogenesis at the shoot apical meristem (SAM) and during lateral organ development.

Keywords: auxin,dorsoventral patterning,morphogenesis,meristem,organ,imaging,cell polarity
Sharing capacity across Europe in high-throughput sequencing technology to explore genetic variation in health and disease (GEUVADIS)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Coordination and support actions
Countries involved: Spain,Switzerland,Germany,United Kingdom,France,Germany,Sweden,Germany,Netherlands,Netherlands,Spain,Germany,Germany,United States
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2010-10-01
End date: 2013-12-31
Duration (months): 39.0
Total project cost (EUR): 2238549.88
EU funding (EUR): 2000000.0
Participants: 17
Project status: CLOSED

High-throughput next-generation DNA sequencing technologies allow investigators to sequence entire human genomes at an affordable price and within a short time frame. The correct interpretation, storage, and dissemination of the large amount of produced genomics data generate major challenges. Tackling these challenges requires extensive exchange of data, information and knowledge between medical scientists, sequencing centres, bioinformatics networks and industry at the European level. The GEUVADIS (genetic European variation in disease) Consortium aims at developing standards in quality control and assessment of sequence data, models for data storage, exchange and access, as well as standards for the handling, analysis and interpretation of sequencing data and other functional genomics datasets, standards for the biological and medical interpretation of sequence data and in particular rare variants for monogenic and common disorders, and finally standards for the ethics of phenotype prediction from sequence variation. The partners are all involved in international sequencing initiatives (1000 GP, ICGC), EU and other international projects (ENGAGE, GEN2PHEN, ENCODE, TECHGENE …), biobanking activities (BBMRI), data sharing initiatives (ELIXIR), and the European Sequencing and Genotyping Infrastructure (ESGI), ensuring tight collaborations. The Consortium will undertake pilot sequencing projects on selected samples from three medical fields (cardiovascular, neurological and metabolic), using RNA (RNASeq) and DNA (exonSeq) sequencing. The analysis of such samples will allow the consortium to set up standards in operating procedures and biological/medical interpretation of sequence data in relation to clinical phenotypes. The consortium will bring together the knowledge and resources on medical genome sequencing at a European level and allow researchers to develop and test new hypotheses on the genetic basis of disease.

Keywords: sequencing technologies,ngs,genetic variation
From neurons to behaviour: Context representation and memory reconsolidation in the entorhinal hippocampal system (RECONTEXT)

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: Netherlands
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-03-01
End date: 2016-02-29
Duration (months): 60.0
Total project cost (EUR): 1474872.0
EU funding (EUR): 1474872.0
Participants: 1
Project status: CLOSED

One of the most intriguing topics in neuroscience and memory research today is ‘reconsolidation’: the phenomenon that a brief reminder renders an already consolidated memory labile again and that this fragile memory requires de novo protein synthesis to be reconsolidated. However, the functional role and the neural mechanisms of reconsolidation in humans are unclear. Another exciting line of research in neuroscience, based on the discovery of spatially tuned hippocampal place and entorhinal grid cells in rodents, suggests that during first exposure to an environment a spatial map-like representation is formed in the entorhinalhippocampal system and it has been proposed that events are then encoded onto this map in their spatial context. By combining the understanding of these two fields of animal research, translating it to systems neuroscience in humans and building on my recent discovery that place-cell and grid-cell like representations exist in humans, I will test the novel idea that these hippocampal and entorhinal representations of spatial context are a clue to understand the mechanisms of memory reconsolidation in humans. To examine this, I will use virtual-reality technologies combined with functional neuroimaging in humans. I will test the prediction that context reexposure leads to a reactivation of consolidated memories in neocortex and investigate the role of entorhinal-hippocampal context representations during memory reconsolidation. I will also examine the functional role and the mechanisms of a dynamic memory representation: How is new information integrated into reactivated memories? Finally, I will investigate conjunctive representations of cortical memories in the hippocampal formation. My eventual aim is to produce a coherent understanding of brain function from neural representations to systems-level involvement in behaviour which might help to understand the neural mechanisms underlying memory impairments in neuro-degenerative diseases.

Keywords: hippocampus,entorhinal cortex,virtual reality,memory,reconsolidation,space
DNA based nanometry: Exploring chromatin structure and molecular motors (DNAMETRY)

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: Germany,Germany,Germany
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-01-01
End date: 2016-10-31
Duration (months): 70.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 3
Project status: CLOSED

DNA metabolism is governed by a delicate balance between compacting the stored genetic information while simultaneously ensuring a highly dynamically access to it. This interdisciplinary project aims (i) to understand the mechanics and dynamics of chromatin as well as the mechanism of enzymes involved in DNA metabolism on a molecular level and (ii) to develop new nanometric tools based on optical methods and 3D DNA nanostructures that allow addressing new experimental questions. Within the research project novel nanoscopic detection assays based on the combination of magnetic tweezers and optical methods shall be developed, such as ultra-fast torque spectroscopy and combined FRET-force spectroscopy. Our single-molecule assays shall be applied to study the material properties of self-assembled 3D DNA nanostructures, which shall then be used to set up improved high resolution single-molecule assays. These technological improvements will become key to obtain insight into structure and dynamics of in vitro reconstituted chromatin as response to external mechanical stress but also into the operation of molecular motors that themselves generate forces and torques on DNA and chromatin. The main goal of the project is to use nanotechnological tools to understand design principles of biomolecules, biomaterials and biological motors, which in turn shall be used to develop smarter nanotools and functional elements.

Keywords: single-molecule biophysics,magnetic tweezers,single-molecule fluorescence,dna nanostructures,dna motor enzymes,helicases,chromatin structure and dynamics
Adipose tissue mass regulation in lean and obese individuals (HUFATREG)

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: Sweden
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-04-01
End date: 2017-03-31
Duration (months): 72.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Owing to the increase in obesity, life expectancy may start to decrease in developed countries for the first time in recent history. In humans the generation of fat cells (adipocytes) is a major factor behind the growth of adipose tissue during childhood. The factors determining the fat mass in adults, however, are not fully understood. Increased fat storage in fully differentiated adipocytes, resulting in enlarged fat cells, is well documented and thought to be the most important mechanism whereby fat depots increase in adults. Very little is known about the maintenance of fat cells (adipocytes) in humans, how different fat depots are maintained and how (or if) this is altered in obesity. Recently I developed a method that is based on the incorporation of 14C from nuclear bomb tests into genomic DNA, which allows for the analysis of cell and tissue turnover in humans. Using this novel methodology we now have a strategy for studying cell turnover in humans. One tissue of great interest and significant clinical relevance is adipose tissue. Excess adipose tissue, resulting in obesity, is currently one of the most serious threats to human health on a global level. The current proposal aims to determine the dynamics of human adipose tissue maintenance and investigate any differences in regulation of the fat mass in lean and obese individuals. Understanding the dynamics of adipocyte turnover may shed new light on potential treatments for obesity.

Keywords: adipose tissue,tissue regulation,adipocyte biology