Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Molecular Mechanisms Regulating Pancreatic Islet Vascularization (ISLETVASC)

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: 2010-11-01
End date: 2015-10-31
Duration (months): 60.0
Total project cost (EUR): 1496257.0
EU funding (EUR): 1496257.0
Participants: 1
Project status: CLOSED

Many reports indicate the number of people with diabetes will exceed 350 million by the year 2030. Both type 1 and type 2 diabetes are characterized by the deterioration and impaired function of pancreatic b-cells. While transplantation is a promising strategy to replace lost tissue, several obstacles remain in the pathway to its clinical application. Whether b-cells are derived from patient samples or differentiated from embryonic stem cells, a major concern facing these strategies is how a recipient will respond to transplanted foreign tissue. Since the native environment for pancreatic islets is comprised of neural and vascular networks, successful integration may depend upon signals received from these neighboring cell types. Using a multidisciplinary approach, the principal investigator plans to elucidate molecular mechanisms underlying the interactions between pancreatic islet cells and their neighboring endothelial cells. Developing an understanding of how these interactions change during the pathogenesis of disease will provide insight into how islet growth and insulin release is dependent upon signals received from adjacent cell types. Emphasis will be placed on genetic mouse models to measure changes in gene expression in both isolated pancreatic b-cells and endothelial cells to identify genes that mediate the interaction between these cell types. In addition, it is of great interest to identify secreted factors that may constitute autocrine or paracrine signalling mechanisms that influence growth and function between these cell types. Furthermore, it will be determined whether current protocols for the differentiation of mouse stem cells into insulin producing cells are improved by restoring the expression of genes which facilitate communication to endothelial cells. This project aims to identify genes essential to the vascular context of pancreatic b-cells to improve transplantation protocols and facilitate the development of therapeutic strategies for diabetes.

Keywords: pancreatic beta cell,micrornas,endothelial cell,islet transplantation
Building an Integrated Genetic Infectious Disease Epidemiology Approach (BIG_IDEA)

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: 2010-11-01
End date: 2015-10-31
Duration (months): 60.0
Total project cost (EUR): 1483080.0
EU funding (EUR): 1483080.0
Participants: 2
Project status: CLOSED

Epidemiology and public health planning will increasingly rely on the analysis of genetic sequence data. The recent swine-derived influenza A/H1N1 pandemic may represent a tipping point in this trend, as it is arguably the first time when multiple strains of a human pathogen have been sequenced essentially in real time from the very beginning of its spread. However, the full potential of genetic information cannot be fully exploited to infer the spread of epidemics due to the lack of statistical methodologies capable of reconstructing transmission routes from genetic data structured both in time and space. To address this urgent need, we propose to develop a methodological framework for the reconstruction of the spatiotemporal dynamics of disease outbreaks and epidemics based on genetic sequence data. Rather than reconstructing most recent common ancestors as in phylogenetics, we will directly infer the most likely ancestries among the sampled isolates. This represents an entirely novel paradigm and allows for the development of statistically coherent and powerful inference software within a Bayesian framework. The methodological framework will be developed in parallel with the analysis of real genetic/genomic data from important human pathogens. We will in particular focus on the 2009 A/H1N1 pandemic influenza, methicilin-resistant Staphylococcus aureus clones (MRSAs), Batrachochytrium dendrobatidis, a fungus currently devastating amphibian populations worldwide. The tools we are proposing to develop are likely to impact radically on the field of infectious disease epidemiology and affect the way infectious emerging pathogens are monitored by biologists and public health professionals.

Keywords: genetic monitoring statistical modelling graph theory
Deciphering the microRNA response to hypoxia (HYPOXICMICRORNAS)

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: Denmark
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-11-01
End date: 2015-10-31
Duration (months): 60.0
Total project cost (EUR): 1478508.0
EU funding (EUR): 1478508.0
Participants: 1
Project status: CLOSED

Maintaining oxygen homeostasis is an essential requirement for all metazoa. Oxygen is required for efficient generation of energy, however, as oxygen levels decrease (hypoxia), cells mount a variety of adaptive responses. Each cell in the body can sense and respond to hypoxia, yet the molecular mechanisms that regulate these responses are only beginning to be delineated. Hypoxia plays crucial roles in the pathophysiology of cancer, neurological dysfunction, myocardial infarction and lung disease. Therefore, the goal of the proposed research is to better understand how cells sense and adapt to hypoxia. To this end, I am using the powerful genetic model of Caenorhabditis elegans to identify novel molecular mechanisms required for oxygen homeostatic responses. A critical regulator of hypoxic responses in all cell types is the conserved hypoxia-inducible factor (HIF-1). In response to a hypoxic insult, HIF-1 transcriptionally regulates a wide variety of target genes to facilitate adaptation. Recent studies indicate that in addition to the canonical HIF-1 pathway, microRNAs (miRNAs) play important roles in hypoxic response mechanisms. miRNAs are regulatory molecules that predominantly repress protein production of their target genes, however, their roles in hypoxic adaptation are poorly understood. I recently found that specific phylogenetically conserved miRNAs are regulated by hypoxia in C. elegans; and that the function of these miRNAs is required for survival of animals in low oxygen conditions. This is truly an emerging field of science and I expect to make groundbreaking discoveries in the regulation of hypoxic and metabolic responses by miRNAs, which will improve our understanding of many disease processes. The proposed research will 1) analyze the functional roles of specific miRNAs in hypoxic responses and 2) utilize immunoprecipitation, bioinformatics and genetic screening combined with state-of-the-art deep sequencing technology to identify novel miRNA targets required for adaptation to hypoxia.

Keywords: microrna,hypoxia,metabolism
Induced Pluripotent stem Cells: A Novel Strategy to Study Inherited Cardiac Disorders (CARDIO-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: Israel
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-03-01
End date: 2016-02-29
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

The study of several genetic disorders is hampered by the lack of suitable in vitro human models. We hypothesize that the generation of patient-specific induced pluripotent stem cells (iPSCs) will allow the development of disease-specific in vitro models; yielding new pathophysiologic insights into several genetic disorders and offering a unique platform to test novel therapeutic strategies. In the current proposal we plan utilize this novel approach to establish human iPSC (hiPSC) lines for the study of a variety of inherited cardiac disorders. The specific disease states that will be studied were chosen to reflect abnormalities in a wide-array of different cardiomyocyte cellular processes. These include mutations leading to: (1) abnormal ion channel function (“channelopathies”), such as the long QT and Brugada syndromes; (2) abnormal intracellular storage of unnecessary material, such as in the glycogen storage disease type IIb (Pompe’s disease); and (3) abnormalities in cell-to-cell contacts, such as in the case of arrhythmogenic right ventricular cardiomyopathy-dysplasia (ARVC-D). The different hiPSC lines generated will be coaxed to differentiate into the cardiac lineage. Detailed molecular, structural, functional, and pharmacological studies will then be performed to characterize the phenotypic properties of the generated hiPSC-derived cardiomyocytes, with specific emphasis on their molecular, ultrastructural, electrophysiological, and Ca2+ handling properties. These studies should provide new insights into the pathophysiological mechanisms underlying the different familial arrhythmogenic and cardiomyopathy disorders studied, may allow optimization of patient-specific therapies (personalized medicine), and may facilitate the development of novel therapeutic strategies. Moreover, the concepts and methodological knowhow developed in the current project could be extended, in the future, to derive human disease-specific cell culture models for a plurality of genetic disorders; enabling translational research ranging from investigation of the most fundamental cellular mechanisms involved in human tissue formation and physiology through disease investigation and the development and testing of novel therapies that could potentially find their way to the bedside

Keywords: induced pluripotent stem cells,arrhythmias,electrophysiology,cardiomyopathy,ion channels,genetic disorders
Untangling the Bacterial Chromosome: Condensin's Role in Sister Chromosome Separation and its Mechanisms. (DISENTANGLE)

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
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-11-01
End date: 2015-10-31
Duration (months): 60.0
Total project cost (EUR): 1376734.0
EU funding (EUR): 1376734.0
Participants: 1
Project status: CLOSED

A prerequisite for chromosome segregation in all living organisms is the topological unlinking of sister DNA molecules, called DNA decatenation. Decatenation is performed by DNA topoisomerases that work by transiently breaking strand(s) in one DNA double helix and passing another double helix through the temporarily created gate. How DNA topoisomerases manage to recognize linkages between sister DNA molecules and how they promote decatenation of sister chromatids (but not catenation) is still largely unknown. The driving hypothesis of this project is that condensin promotes chromosome decatenation by guiding the unlinking activity of DNA topoisomerases. Condensin is a member of the family of SMC (Structural Maintenance of Chromosomes) protein complexes that is conserved from bacteria to humans. It forms large, ring-like structures that bind to and organize chromosomes. Efficient separation of sister chromosomes in the bacterium B. subtilis depends on the condensin complex. However, so far the precise role of condensin in chromosome segregation and its mechanisms are unclear. To test our hypothesis, we will establish a minichromosome in bacteria that segregates in a condensin-dependent manner and measure its decatenation in vivo in the presence and absence of condensin. We will investigate the mechanism by which condensin organizes DNA within the (mini-)chromosome using techniques like chromosome conformation capture (3C) and electron microscopy. Finally, we will attempt to reconstitute for the first time the entrapment of DNA double helices by ring-like SMC protein complexes using purified components. Our results will be pivotal for understanding the action of SMC proteins in general with important implications in the separation and segregation of chromosomes in bacteria, the shaping of mitotic chromosomes and the resolution of sister chromatids during mitosis in eukaryotes.

Keywords: condensin,chromosome,decatenation,smc,kleisin
Communication Motifs: Principles of bacterial communication in non-genetically diversified populations (COMMOTS)

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: Germany
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-09-01
End date: 2016-08-31
Duration (months): 60.0
Total project cost (EUR): 1496840.0
EU funding (EUR): 1496840.0
Participants: 1
Project status: CLOSED

Cell-to-cell communication is a central aspect for understanding how cells form and organize multi-cellular communities involving progressive cell specialization. Multi-cellularity cell specialization cell communication those keywords are frequently used to distinguish metazoans from bacteria. Yet bacteria can form morphologically complex multi-cellular communities, they can non-genetically diversify and they can communicate. This implies that even prokaryotic networks must possess the properties to facilitate these complex functions. Thus basic network features ( motifs ) determining these functions can be discovered and characterized from studying simpler bacterial networks. We want to focus on communication motifs that are present in the gene-regulatory network of Bacillus subtilis. Our proposed methodology involves a combination of quantitative fluorescence microscopy techniques (QFTLM, FRET), developmental assays, signal transduction studies in controlled micro-environments and information theory to quantitatively characterize communication motifs..

Keywords: quorum sensing,heterogeneity,information theory,bacillus subtilis,sporulation
Evolutionary reconstruction of viral spread in time and space (VIRALPHYLOGEOGRAPHY)

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: Belgium,United States,United Kingdom
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-10-01
End date: 2015-09-30
Duration (months): 60.0
Total project cost (EUR): 1498915.16
EU funding (EUR): 1498915.16
Participants: 3
Project status: CLOSED

To identify the causal mechanisms leading to disease emergence, endemic maintenance and epidemic expansion, epidemiologists would benefit tremendously from a full characterization of pathogen spread in space and time. The extensive sequencing efforts for the ongoing swine-origin H1N1 influenza A epidemic testify that analyses of pathogen genetic data are becoming increasingly important source of information in epidemiology. The new era of metagenomics promises to harvest such data in unprecedented quantities with remarkable rapidity. With the objective to assist in designing effective intervention and prevention strategies, we propose to develop a comprehensive statistical framework for uncovering the spatial and temporal dynamics of pathogen genomes. To this aim, we will design and extend a series of computationally tractable models that use the rapidly proliferating viral genome data to their full potential, connect molecular evolution to underlying spatial processes, and pave the path to rigorous and powerful phylogeographic hypothesis testing approaches. Armed with these tools, we will investigate how genetic variation within important viral pathogens, such as influenza, rabies and HIV, arises and persists across a diverse range of hosts and environments.

Keywords: molecular epidemiology phylogeography
Aging Differently: Understanding Sex Differences in Reproductive, Demographic and Functional Senescence (AGINGSEXDIFF)

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: Sweden
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-12-01
End date: 2016-05-31
Duration (months): 66.0
Total project cost (EUR): 1391904.0
EU funding (EUR): 1391904.0
Participants: 1
Project status: CLOSED

Sex differences in life span and aging are ubiquitous across the animal kingdom and represent a long-standing challenge in evolutionary biology. In most species, including humans, sexes differ not only in how long they live and when they start to senesce, but also in how they react to environmental interventions aimed at prolonging their life span or decelerating the onset of aging. Therefore, sex differences in life span and aging have important implications beyond the questions posed by fundamental science. Both evolutionary reasons and medical implications of sex differences in demographic, reproductive and physiological senescence are and will be crucial targets of present and future research in the biology of aging. Here I propose a two-step approach that can provide a significant breakthrough in our understanding of the biological basis of sex differences in aging. First, I propose to resolve the age-old conundrum regarding the role of sexspecific mortality rate in sex differences in aging by developing a series of targeted experimental evolution studies in a novel model organism – the nematode, Caenorhabditis remanei. Second, I address the role of intra-locus sexual conflict in the evolution of aging by combining novel methodology from nutritional ecology – the Geometric Framework – with artificial selection approach using the cricket Teleogryllus commodus and the fruitfly Drosophila melanogaster. I will directly test the hypothesis that intra-locus sexual conflict mediates aging by restricting the adaptive evolution of diet choice. By combining techniques from evolutionary biology and nutritional ecology, this proposal will raise EU’s profile in integrative research, and contribute to the training of young scientists in this rapidly developing field.

Keywords: aging,senescence,life-history evolution
Real-Time Studies of Biological NanoMachines in Action by NMR (SEENANOLIFEINACTION)

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: France
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-01-01
End date: 2015-12-31
Duration (months): 60.0
Total project cost (EUR): 1398392.0
EU funding (EUR): 1398392.0
Participants: 1
Project status: CLOSED

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Keywords: nmr methodology,isotopic labelling,proteins assembies,self-assembling,substrate cleavage
Telomeres: from the DNA end replication problem to the control of cell proliferation (D-END)

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: France
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-11-01
End date: 2015-10-31
Duration (months): 60.0
Total project cost (EUR): 1498503.6
EU funding (EUR): 1498503.6
Participants: 1
Project status: CLOSED

Linear chromosomes of eukaryotes end with telomeres that ensure their stability. Because of the inability of semi-conservative DNA replication machinery to fully replicate DNA ends, telomeres require dedicated mechanisms to be duplicated and their length is eroded at each cell division. For this reason, telomeres constitute molecular clocks that determine cell proliferation potential in eukaryotes. Strikingly, we have shown recently that it is the shortest telomere in the cell that determines the onset of replicative senescence. This project aims a complete and detailed dissection of the in vivo DNA-end replication problem and the deep understanding of its impact for cell division capability. Specifically my goals are (1) the determination of the exact structures that result from the replication of DNA extremities, (2) the examination of the activities operating at the shortest telomere that triggers replicative senescence and (3) the investigation of the correspondence between telomere molecular structure and cell proliferation state at individual cell scale. To achieve this, I will undertake in Saccharomyces cerevisiae original and innovative single-molecule and single-cell approaches, that, in combination with genome-wide screens and sophisticated cellular settings, will allow to track and challenge a specified telomere of defined length. I anticipate that this work will lead to an in-depth understanding of how telomeres are replicated and how they enable the control of cell proliferation in eukaryotic cells, a matter at the intersection of the fundamentals of molecular genetics, cell biology of aging and oncology.

Keywords: telomere,telomerase,cell cycle,dna damage checkpoints,dna replication,dna repair,dna recombination,non-coding rna