Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Genome, the Edited Version: DNA and RNA Editing of Mammalian Retroelements (GENDEVER)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Genetics,Genomics,Bioinformatics and Systems Biology
Countries involved: Israel
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2012-10-01
End date: 2017-09-30
Duration (months): 60.0
Total project cost (EUR): 1499249.0
EU funding (EUR): 1499249.0
Participants: 1
Project status: CLOSED

It is generally thought that an organism contains the exactly same genomic information in all its cells and that a genome remains unaltered throughout the organism’s life, with the exception of rare and random somatic mutations that might occur. This genomic information will also serve as a template for exact RNA copies. However, endogenous and powerful means of creating inner genomic diversity are known to exist: (1) RNA editing that leads to alteration of one nucleotide into another, (mainly A-to-I); (2) DNA editing that changes the DNA’s content by shifting C-into-U; (3) active retroelements that can insert copies of their sequences into new locations in a genome. Recently, we and others have found that although considered extremely rare, all three mechanisms are active somatically or at least leave traces of their occurrence in the genome, and are linked together, as most editing events occur in retroelements. However, the magnitude and scope of these mechanisms, which can lead to huge diversity and complexity within an organism and even within a cell, are still a mystery. This explosion of genomic variety can have dramatic effect on diverse biological processes, such as brain complexity, cancer and evolution acceleration. In GENEDVER, we aim to perform the first genome-wide mapping of editing and active retroelements in various genomes using a combination of computational and genomic approaches. Specifically, we will develop a strategy to detect RNA and DNA editing in retroelements, scan for editing events in various genomes, and build the first global editing atlas. In addition, we will exploit the close association between editing and retroelements in to produce a genome-wide approach to detect active retroelements. Finally, we will screen for editing events and retrotranspositions in various biological conditions, in order to expose their involvement in many biological states and evolution.

Keywords: rna-editing,retroelements,dna-editing
Origins and factors governing adaptation: Insights from experimental evolution and population genomic data (ADAPT)

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: Denmark
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-04-01
End date: 2018-03-31
Duration (months): 60.0
Total project cost (EUR): 1159857.0
EU funding (EUR): 1159857.0
Participants: 1
Project status: CLOSED

I propose a systematic study of the type of genetic variation enabling adaptation and factors that limit rates of adaptation in natural populations. New methods will be developed for analysing data from experimental evolution and population genomics. The methods will be applied to state of the art data from both fields. Adaptation is generated by natural selection sieving through heritable variation. Examples of adaptation are available from the fossil record and from extant populations. Genomic studies have supplied many instances of genomic regions exhibiting footprint of natural selection favouring new variants. Despite ample proof that adaptation happens, we know little about beneficial mutations– the raw stuff enabling adaptation. Is adaptation mediated by genetic variation pre-existing in the population, or by variation supplied de novo through mutations? We know even less about what factors limit rates of adaptation. Answers to these questions are crucial for Evolutionary Biology, but also for believable quantifications of the evolutionary potential of populations. Population genetic theory makes predictions and allows inference from the patterns of polymorphism within species and divergence between species. Yet models specifying the fitness effects of mutations are often missing. Fitness landscape models will be mobilized to fill this gap and develop methods for inferring the distribution of fitness effects and factors governing rates of adaptation. Insights into the processes underlying adaptation will thus be gained from experimental evolution and population genomics data. The applicability of insights gained from experimental evolution to comprehend adaptation in nature will be scrutinized. We will unite two very different approaches for studying adaptation. The project will boost our understanding of how selection shapes genomes and open the way for further quantitative tests of theories of adaptation.

Keywords: fitness landscape,experimental evolution,fitness,nucleotide polymorphism
Mechanisms that prevent aneuploidy (NOANEUPLOIDY)

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: France
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-01-01
End date: 2017-12-31
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

The mechanisms that safeguard cells against aneuploidy are of great interest as aneuploidy contributes to tumorigenesis. To gain insight into these mechanisms, I studied the behavior of cells entering mitosis with damaged chromosomes. I used the endonuclease I-CreI to generate acentric chromosomes in Drosophila larvae. While I-CreI expression produces acentric chromosomes in the majority of dividing cells, remarkably, it has no effect on adult survival. Live studies reveal that acentric chromatids segregate efficiently to opposite poles. The acentric chromatid poleward movement is mediated through DNA tethers that connect the acentric fragment to its centric partner. Three highly conserved kinases, BubR1, Aurora B and Polo localize on the tether and facilitates the accurate segregation of acentric chromatids by maintaining the integrity of the tether. Chromosome segregation must be tightly coordinated with cell division to ensure that cells do not divide before the chromosomes have cleared the cleavage plane. However, the mechanism that permits this coordination is unknown. To identify this mechanism, I studied the behavior of cells going through mitosis with abnormally long chromatids. I took advantage of my previous discovery that acentric chromosomes remain attached to their centric partners by a DNA tether. This tether effectively increases the size of sister chromatids during anaphase. Remarkably, the cell adapts to the size of the long chromatids by increasing in length. Cell elongation enables long chromatids to clear the cleavage plane in time for cell division to occur properly. This novel cell elongation mechanism involves myosin activity. I have discovered two mechanisms that prevent aneuploidy: the tether-based acentric segregation and the elongation of the cell that clears chromatids from the cleavage plane. Since both are new processes, our understanding of the underlying mechanisms is limited. My proposal aims to decipher these mechanisms.

Keywords: mitosis,checkpoints,dna damage,chromosome segregation,cytokinesis
NutrImmune: Nutrient-controlled molecular pathways instructing development and function of mucosa-associated innate lymphocytes (NUTRIMMUNE)

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: Germany,Germany
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-03-01
End date: 2018-02-28
Duration (months): 60.0
Total project cost (EUR): 1499760.0
EU funding (EUR): 1499760.0
Participants: 3
Project status: CLOSED

The last decade has witnessed an explosion of research into the molecular networks ensuring maintenance of a mutualistic relationship between microbes and host cell networks at mucosal surfaces. Failure of such homeostatic or adaptive programs lead to susceptibility to intestinal infections or to chronic inflammation causing debilitating human diseases such as inflammatory bowel diseases or inflammation-induced intestinal cancer. In contrast to the role of the microbiota and its composition, the role of nutrients for development and function of the intestinal immune system has been a matter of speculation owing to the fact that molecular sensors of dietary molecules were widely unknown. Given the broad impact of nutrients on metabolic diseases and human health, research into the question of how the power of nutrients can be harnessed for improving human health and for the prevention of disease is much warranted. We have recently found that the aryl hydrocarbon receptor (AhR) is required for the development and function of an innate lymphocyte subset (RORγt+ ILC) that protects against intestinal infections and inflammatory bowel disease (Kiss, Science 2011). AhR serves as a ligand-inducible transcription factor sensing plant-derived phytochemicals and directly controls expression of genes required for the maintenance of RORγt+ ILC. The data established the first molecular link between diets and the development of immune system components. Here, we will test our central hypotheses that (1) diets adapt the function of the intestinal immune system by controlling the pool size of innate lymphocytes, and that (2) RORγt+ ILC directly control epithelial homeostasis and adaptation by regulating niche programs that control intestinal stem cell population dynamics. These aims link nutrient-controlled function of innate lymphocytes to the processes regulating organ homeostasis and may reveal new potential therapeutic strategies for intestinal diseases and cancer.

Keywords: innate immunity,innate lymphoid cells,mucosal immunity,epithelial cell biology
Glia, Smell, Food & Courtship in Drosophila (GLISFCO)

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: France
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2012-11-01
End date: 2017-10-31
Duration (months): 60.0
Total project cost (EUR): 1499999.6
EU funding (EUR): 1499999.6
Participants: 1
Project status: CLOSED

Odors are key components for sensory communication involved in behaviors such as social communication or food search. Recently, molecular receptors, neuronal architecture, physiological regulation, and behavioral consequences underlying these biological processes are starting to be revealed in an increasing number of animal models. But more and more breakthroughs are highlighting some unexpected results asking for deeper studies. The Drosophila melanogaster has proven to be a particular powerful tool to understand, to test, and to manipulate the complex neurogenetical interactions between molecular and cellular partners controlling such behaviors. We have shown that a subset of glia is mastering the activity of a population of neurons involved in chemoperception in Drosophila (e.g. glutamatergic neurons). We have also recently uncovered a striking molecular and neuronal architecture regulating courtship using food odors instead of classical pheromones in fruit flies. Our emerging team at the CSGA-UMR 6265 CNRS will expand these pioneer works to understand how glia and neurons are interacting to impact fly chemosensory choice. For this aim, we will develop powerful genetic tools in Drosophila to reveal and to manipulate the communication between glial cells and neurons in peripheral sensory organs and in projection centers in the brain. We will also look for conserved mechanisms in other insect species (mosquito). The expected data are susceptible to touch a large scientific public since olfaction plays a key sensory modality in most animal species. The collected data on glial function in neuronal activity control will have also a strong impact on finding new strategies to understand neuronal disorders in humans.

Keywords: glia,olfaction,drosophila,courtship,food
Following the Genomic Footprints of Early Europeans (FLOWGENE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Genetics,Genomics,Bioinformatics and Systems Biology
Countries involved: Sweden
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2012-10-01
End date: 2017-09-30
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Two of greatest challenges of the post-genomic era are to (i) develop a detailed understanding of the heritable variation in the human genome, and to (ii) determine which key events in human evolutionary history that are responsible for patterns of genomic variation. The recent genomic revolution will be instrumental in these quests and we will very soon have access to several thousand complete genomes from diverse populations. Extracting genetic information from ancient material has for long been hampered by numerous difficulties after its first steps some two decades ago, but in the last few years, many of these problems have been solved and the use of ancient DNA is now beginning to show its full potential. The use of ancient DNA has been announced among the top-ten ‘insights of the decade’ by Science, and promises to transform our views on human origins and prehistory. The demographic history of Europeans attracts great interest in archaeology, anthropology, and human genetics, and it has drawn extensive research focus for more than a century. The recent genomic revolution has opened up the time dimension for genomic analyses, however, to harness the full potential of genomic data from modern and ancient material, we need new population genetic theory and modern statistical analysis tools. I propose to conduct 3 Ancient Genome Projects to generate complete genomes for multiple individuals from 3 time epochs in the European prehistory; the Cro-Magnon-, the Mesolithic-, and the Neolithic-Genome project. These Genome Projects will proceed in concert with development a) new population genetic theory and novel tools for demographic inference, b) a novel, temporal based, framework for characterizing selection and local adaptation, and c) explore the evolutionary history of gene-variants associated with traits and diseases. Genomic data from temporal samples has the potential to revolutionize our understanding of human evolution and the demographic history of Europe.

Keywords: human evolution,anthropology,evolutionary genetics
Dissecting the Role of Dendrites in Memory (DEMORY)

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: Greece
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2012-10-01
End date: 2018-09-30
Duration (months): 72.0
Total project cost (EUR): 1398000.0
EU funding (EUR): 1398000.0
Participants: 1
Project status: CLOSED

Understanding the rules and mechanisms underlying memory formation, storage and retrieval is a grand challenge in neuroscience. In light of cumulating evidence regarding non-linear dendritic events (dendritic-spikes, branch strength potentiation, temporal sequence detection etc) together with activity-dependent rewiring of the connection matrix, the classical notion of information storage via Hebbian-like changes in synaptic connections is inadequate. While more recent plasticity theories consider non-linear dendritic properties, a unifying theory of how dendrites are utilized to achieve memory coding, storing and/or retrieval is cruelly missing. Using computational models, we will simulate memory processes in three key brain regions: the hippocampus, the amygdala and the prefrontal cortex. Models will incorporate biologically constrained dendrites and state-of-the-art plasticity rules and will span different levels of abstraction, ranging from detailed biophysical single neurons and circuits to integrate-and-fire networks and abstract theoretical models. Our main goal is to dissect the role of dendrites in information processing and storage across the three different regions by systematically altering their anatomical, biophysical and plasticity properties. Findings will further our understanding of the fundamental computations supported by these structures and how these computations, reinforced by plasticity mechanisms, sub-serve memory formation and associated dysfunctions, thus opening new avenues for hypothesis driven experimentation and development of novel treatments for memory-related diseases. Identification of dendrites as the key processing units across brain regions and complexity levels will lay the foundations for a new era in computational and experimental neuroscience and serve as the basis for groundbreaking advances in the robotics and artificial intelligence fields while also having a large impact on the machine learning community.

Keywords: dendritic computations,dendritic spikes,dendritic non-linearity,memory models,hippocampus,amygdala,prefrontal cortex,fear memory allocation,sustained activity,synaptic plasticity models
Assembly and function of the crenarchaeal flagellum (ARCHAELLUM)

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: Germany,Germany
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-02-01
End date: 2018-01-31
Duration (months): 60.0
Total project cost (EUR): 1464317.0
EU funding (EUR): 1464317.0
Participants: 2
Project status: CLOSED

Archaea constitute the third domain of life and are believed to be close to the origin of life. They comprise a diverse group of micro-organisms that combine bacterial and eukaryotic features, but also employ many novel mechanisms. They possess a unique cell envelope with a cytoplasmic membrane of ether lipids surrounded by a proteinaceous S-layer and various cell appendages such as flagella, pili and more unusual structures. Studies have shown that the archaeal flagellum is an unique structure as it functionally resembles the bacterial flagellum, but structurally it is a simple type IV pilus. Moreover, we have shown that this type IV pilus can rotate. Therefore I propose to name the archaeal flagellum, the archaellum, as it is fundamentally different from the bacterial flagellum. In this proposal I aim to understand the assembly and mechanism of rotation of the archaellum of the thermocacidophilic crenarchaen Sulfolobus acidocaldarius by using biochemical, genetic and biophysical methods. The main milestons are: - Biochemical and structural characterization of all archaellum subunits - To understand the assembly pathway of the archaellum and the interactions of its different subunits - To understand how rotation of the filament is achieved and which subunits are important for this movement This work will identify a new, relatively simple motor complex that has evolved from primordial type IV pili assembly machineries and therefore uncover general principles of macromolecular assemblies at cellular surfaces and a novel mechanism to generate mechanical force that can be translated into movement.

Keywords: archaea,biochemistry,protein structure,crystallography,type iv pili,assembly of macromolecular structures,flagella,molecular biology
RNA-based regulation of signal transduction – Regulation of calcineurin/NFAT signaling by microRNA-based mechanisms (CALMIRS)

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: Netherlands
Call:  (ERC-2012-StG_20111109, 2012)
Start date: 2013-02-01
End date: 2018-01-31
Duration (months): 60.0
Total project cost (EUR): 1499528.0
EU funding (EUR): 1499528.0
Participants: 1
Project status: CLOSED

Heart failure is a serious clinical disorder that represents the primary cause of hospitalization and death in Europe and the United States. There is a dire need for new paradigms and therapeutic approaches for treatment of this devastating disease. The heart responds to mechanical load and various extracellular stimuli by hypertrophic growth and sustained pathological hypertrophy is a major clinical predictor of heart failure. A variety of stress-responsive signaling pathways promote cardiac hypertrophy, but the precise mechanisms that link these pathways to cardiac disease are only beginning to be unveiled. Signal transduction is traditionally concentrated on the protein coding part of the genome, but it is now appreciated that the protein coding part of the genome only constitutes 1.5% of the genome. RNA based mechanisms may provide a more complete understanding of the fundamentals of cellular signaling. As a proof-of-principle, we focus on a principal hypertrophic signaling cascade, cardiac calcineurin/NFAT signaling. Here we will establish that microRNAs are intimately interwoven with this signaling cascade, influence signaling strength by unexpected upstream mechanisms. Secondly, we will firmly establish that microRNA target genes critically contribute to genesis of heart failure. Third, the surprising stability of circulating microRNAs has opened the possibility to develop the next generation of biomarkers and provide unexpected mechanisms how genetic information is transported between cells in multicellular organs and fascilitate inter-cellular communication. Finally, microRNA-based therapeutic silencing is remarkably powerful and offers opportunities to specifically intervene in pathological signaling as the next generation heart failure therapeutics. CALMIRS aims to mine the wealth of these RNA mechanisms to enable the development of next generation RNA based signal transduction biology, with surprising new diagnostic and therapeutic opportunities.

Keywords: microrna,signal transduction,heart failure