Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Identifying the immune and microbial network controlling the IL-22 – IL-22bp axis to open the doors for targeted therapies (IL-22 AND IL-22BP)

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-2013-StG, 2013)
Start date: 2014-01-01
End date: 2018-12-31
Duration (months): 60.0
Total project cost (EUR): 1498392.0
EU funding (EUR): 1498392.0
Participants: 2
Project status: CLOSED

Chronic mucosal inflammation and tissue damage predisposes patients to the development of colorectal cancer. One hypothesis is that the same factors important for wound healing, if left unchecked, also promote tumorigenesis. Tight control by a sensor of tissue damage should induce these factors to promote tissue repair, while limiting their activity to prevent development of cancer. IL-22, a prototypical tissue repair factor, plays an important role in a wide variety of intestinal disease including infection, wound healing, colitis, and cancer. Indeed, IL-22 has protective and detrimental effects dependent on the milieu and disease suggesting that proper regulation is required. IL-22 expression is directly regulated, additionally a soluble IL-22 receptor (IL-22 binding protein; IL-22bp), can bind and neutralize IL-22. We reported recently that sensing of intestinal tissue damage and components of the microbiota via the NLRP3 or NLRP6 inflammasomes led to a down regulation of IL-22bp, thereby increasing bioavailability of IL-22. IL-22, which is induced during intestinal tissue damage, exerted protective properties during the peak of damage, but promoted tumor development if not controlled by IL-22bp during the recovery phase. Accordingly a spatial and temporal regulation of IL-22 is crucial. Hence, global administration or blockade of IL-22 is unlikely to be therapeutically beneficial. We are using several newly generated conditional knock-out (cCasp1-/-, cIL-18R-/-, cIL-18-/-, cIL-22R1-/-), knock-in (IL-22 BFP), and gnotobiotic mice, aiming to analyze the cellular and microbial network regulating the IL-22 – IL-22bp axis at a resolution previously unfeasible. Our results will provide novel insights into the network between microflora, epithelium, and immune system regulating tissue regeneration and tumor development, and can lead to therapies for potentially a wide variety of intestinal diseases, such as infection, colon cancer, IBD, or wound healing.
An integrated assessment of recent evolutionary change through genome wide mapping of regulatory changes and signatures of selection in natural sculpin (Cottus) hybrids (EVOLMAPPING)

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: Germany
Call:  (ERC-2013-StG, 2013)
Start date: 2014-02-01
End date: 2019-01-31
Duration (months): 60.0
Total project cost (EUR): 1377162.0
EU funding (EUR): 1377162.0
Participants: 2
Project status: CLOSED

It is the unprecedented access to genome wide data that highlights the potential of current evolutionary studies and this proposal aims at exploiting this progress to analyze evolutionary processes in a well-established fish system of hybrid speciation. We study natural populations of freshwater fish referred to as sculpins (Cottus). In these we have identified species that have recently (<200 years) hybridized as a result of secondary contact through man-made canals between river systems. This gave rise to a new lineage with new adaptations that have allowed it to invade habitats that were not used by the parental species before. We are thus also dealing with evolutionary change that is associated with man-made ecological perturbations, the analysis of which is particularly timely. It is now possible to perform a near exhaustive search to identify genes and to study gene expression as a measure of evolutionary change in Cottus. A combination of genetic mapping experiments and screens for genotypic selection can reveal loci and functions as targets of selection in the adaptive evolution of invasive Cottus. This proposal specifically aims at identifying genomic traits such as copy number changes of coding sequences or changes in the gene regulatory architecture that have evolved as a direct consequence of hybridization and to explore their implication in adaptive evolution. The results will contribute to our understanding of the genetics of adaptation and the invasion of a new environment. With respect to hybrid zones and the evolution of new species, we will identify candidate genes and functions that can explain barriers to reproduction in the wild. Finally, we will be able to make significant progress with respect to the genetics associated with hybrid speciation.

Keywords: hybrid speciation,admixture,invasive species,ecological change,adaptive evolution,copy number variation,whole genome analysis
Noise in gene expression as a determinant of virulence of the human pathogen Streptococcus pneumoniae (PNEUMOCELL)

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: Netherlands
Call:  (ERC-2013-StG, 2013)
Start date: 2013-11-01
End date: 2018-10-31
Duration (months): 60.0
Total project cost (EUR): 1498846.0
EU funding (EUR): 1498846.0
Participants: 1
Project status: CLOSED

Not all cells in bacterial populations exhibit exactly the same phenotype, even though they grow in the same environment and are genetically identical. One of the main driving forces of phenotypic variation is stochasticity, or noise, in gene expression. Possible molecular origins contributing to noise in protein synthesis are stochastic fluctuations in the biochemical reactions of gene expression itself, namely transcription and translation. The driving hypothesis of this application is that the human pathogen Streptococcus pneumoniae utilizes noisy gene expression to successfully colonize and invade its host. To test this supposition, the total amount of noise in key regulatory networks for virulence factor production will be quantified. Using natural and synthetic bistable switches as highly sensitive probes for noise, in combination with state-of-the-art single-cell imaging, microfluidics and direct transcriptome sequencing, the molecular mechanisms underlying noise generation in S. pneumoniae will be determined. By constructing strains with altered levels of phenotypic variation, the importance of noisy gene expression in S. pneumoniae pathogenesis will be tested. S. pneumoniae is a leading cause of bacterial pneumoniae, meningitis, and sepsis worldwide. The molecular mechanisms that cause switching of S. pneumoniae to its virulent states are barely understood, although it becomes increasingly clear that noise-driven phenotypic variation plays an important role in pneumococcal pathogenesis. Therefore, understanding the molecular origins of phenotypic variation in S. pneumoniae might not only provide novel fundamental insights in gene expression, but also result in the identification of new anti-pneumococcal targets.

Keywords: streptococcus pneumoniae,stochasticity,bistability,rna-seq,orthogonal transcription,single cell analysis,noise,microfluidics
Long Intervening Noncoding RNAs (lincRNAs): Developmental Functions and Molecular Mechanisms of Action (FLAME)

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: France
Call:  (ERC-2013-StG, 2013)
Start date: 2014-02-01
End date: 2019-07-31
Duration (months): 66.0
Total project cost (EUR): 1499976.0
EU funding (EUR): 1499976.0
Participants: 1
Project status: CLOSED

Genome-wide studies have revealed that the majority of vertebrate genomes are transcribed and generate large numbers of long intervening noncoding RNAs (lincRNAs). While there is growing evidence that these molecules have functional importance for diverse cellular processes, such as dosage compensation, transcriptional regulation, and reprogramming, the role of lincRNAs in normal development remains elusive. To better understand the function and evolution of lincRNAs, we previously identified over 550 lincRNAs expressed during zebrafish embryonic development. We demonstrated that at least two of these novel lincRNAs, megamind and cyrano, are required for proper embryonic development, in particular for brain morphogenesis and neurogenesis. Remarkably, lincRNA functionality is retained in mammalian orthologs despite rapid evolution and little sequence conservation between human and zebrafish lincRNAs (Ulitsky*, Shkumatava* et al., Cell, 2011). This proposal aims to identify conserved developmental functions of novel lincRNAs and to determine the molecular mechanisms that drive these lincRNA functions (Aims 1 and 2). For mechanistic studies, the initial focus will be on cyrano and megamind. Preliminary evidence suggests that one of these novel molecular mechanisms is through a non-canonical interaction between cyrano and the miRNA pathway (Aim 3). Furthermore, we will investigate the relationship between conserved genomic positions of lincRNAs across vertebrate genomes and their conserved biological functions (Aim 4). The specific aims outlined in this proposal will identify novel regulatory RNAs with important and potentially conserved roles in vertebrate embryonic development, and provide mechanistic insights into how specific lincRNA contribute to normal development. Moreover, we anticipate that this project will contribute to a new synthesis of knowledge of genome function and regulation.

Keywords: noncoding rnas,regulatory rnas,vertebrate development
DAtacommunications based on NanophotoniC Resonators (DANCER)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Systems and communication engineering
Countries involved: United Kingdom
Call:  (ERC-2013-StG, 2013)
Start date: 2013-12-01
End date: 2019-05-31
Duration (months): 66.0
Total project cost (EUR): 1495450.0
EU funding (EUR): 1495450.0
Participants: 2
Project status: CLOSED

A key challenge for the 21st century is, therefore to provide billions of people with the means to access, move and manipulate, what has become, huge volumes of information. The environmental and economic implications becoming serious, making energy efficient data communications key to the operation of today’s society. In this project, the Principal Investigator will develop a new framework for optical interconnects and provide a common platform that spans Fibre-to-the-home to chip-to-chip links, even as far as global on-chip interconnects. The project is based on the efficient coupling of the Photonic Crystal resonators with the outside world. These provide the ultimate confinement of light in both space and time allowing orders of magnitude improvements in performance relative to the state of the art, yet in a simpler simple system- the innovator’s dream. New versions of the key components of optical links- light sources, modulators and photo-detectors- will be realised in this new framework providing a new paradigm for energy efficient communication.
Taking extrasolar planet imaging to a new level with vector vortex coronagraphy (VORTEX)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Universe sciences
Countries involved: Belgium,Sweden
Call:  (ERC-2013-StG, 2013)
Start date: 2013-09-01
End date: 2018-08-31
Duration (months): 60.0
Total project cost (EUR): 1499200.0
EU funding (EUR): 1499200.0
Participants: 2
Project status: CLOSED

Vector vortex coronagraphs (VVC) are among the most promising solutions to directly image faint extrasolar planets by dimming the glare of their nearby host star. Manufacturing and efficiently operating such devices is however a challenging enterprise, especially in the thermal infrared regime where warm planets radiate most of their energy. For several years, we have been developing a new class of VVC, called the Annular Groove Phase Mask (AGPM) coronagraph. Etched on a diamond substrate, this coronagraph can be operated at any wavelength, including the thermal infrared, thanks to the excellent transparency properties of diamond. We are now at a stage where the first components have been manufactured and tested. The proposed research program has three main goals. First, we will install and exploit the first generation of AGPM coronagraphs on large telescopes in world-leading observatories. By providing a means to efficiently cancel the starlight in the thermal infrared regime for the first time, our AGPMs will significantly contribute to the discoveries and characterisation of exoplanets beyond a few astronomical units. Second, we aim at developing new AGPM coronagraphs for the next generation of imaging instruments. We will particularly focus our developments on the instruments planned for the future extremely large telescopes, which will bring the direct imaging of exoplanets to a new level. Finally, we will study, develop and test a ground-breaking concept that could improve very significantly the on-sky performance of VVCs in general. This concept is based on the quantum properties of light and in particular on the fact that an optical vortex induces an orbital angular momentum on the input starlight. We propose to use an interferometric device to sort photons based on their orbital angular momentum, so as to separate the planetary light from the residual starlight (including the speckles created by atmospheric turbulence) at the output of the coronagraph.

Keywords: extrasolar planets,circumstellar disks,high angular resolution,coronagraphy,interferometry
Demographic and Phenotypic Signals of Population Responses to Environmental Change (SPREC)

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: Switzerland
Call:  (ERC-2013-StG, 2013)
Start date: 2013-12-01
End date: 2018-11-30
Duration (months): 60.0
Total project cost (EUR): 1499136.0
EU funding (EUR): 1499136.0
Participants: 1
Project status: CLOSED

A major goal in biodiversity conservation is to predict responses of biological populations to environmental change. To achieve this, we must identify early warning signals of the demographic changes that underlie population declines. Some studies have achieved phenomenological prediction of sudden changes, but recent advances that link trait-based information with demography hint that a mechanistic understanding is within reach. I propose to develop a predictive framework by identifying the demographic and phenotypic statistics that can be used as early warning signals of demographic regime shifts. I have investigated links between ecological and evolutionary processes in changing environments for many years, and I will now build on this experience to develop a predictive theory. First, we will analyse unique long-term individual-based datasets from nine mammal species. The species represent a continuum of life histories and environmental conditions, and some of them show population dynamic regime shifts. Second, we will construct trait-based demographic models of each system and perturb key parameters to simulate population and trait dynamics under multiple environmental scenarios. The simulations will yield time-series data from which we will estimate demographic and phenotypic statistics. We will test the ability of these statistics to predict demographic changes using a novel decision algorithm framework. Finally, using two laboratory microcosms, we will experimentally test the ability of these statistics to predict population responses to environmental change. This project will exploit nine unique natural systems to identify early warning signals of population change and test these on two experimental systems. Results will provide much-needed predictive insight into how wildlife populations respond to environmental change, and will be of highest importance to management of wildlife populations whether they are of conservation concern, invasive, or exploitable.

Keywords: population dynamics,trait-based demography,eco-evolutionary dynamics,environmental change,integral projection models,individual-based models,experimental ecology,early warning signals
Beads on String Genomics: Experimental Toolbox for Unmasking Genetic / Epigenetic Variation in Genomic DNA and Chromatin (BEADSONSTRING)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Physical and Analytical Chemical sciences
Countries involved: Israel
Call:  (ERC-2013-StG, 2013)
Start date: 2013-10-01
End date: 2019-09-30
Duration (months): 72.0
Total project cost (EUR): 1627600.0
EU funding (EUR): 1627600.0
Participants: 1
Project status: CLOSED

Next generation sequencing (NGS) is revolutionizing all fields of biological research but it fails to extract the full range of information associated with genetic material and is lacking in its ability to resolve variations between genomes. The high degree of genome variation exhibited both on the population level as well as between genetically “identical” cells (even in the same organ) makes genetic and epigenetic analysis on the single cell and single genome level a necessity. Chromosomes may be conceptually represented as a linear one-dimensional barcode. However, in contrast to a traditional binary barcode approach that considers only two possible bits of information (1 & 0), I will use colour and molecular structure to expand the variety of information represented in the barcode. Like colourful beads threaded on a string, where each bead represents a distinct type of observable, I will label each type of genomic information with a different chemical moiety thus expanding the repertoire of information that can be simultaneously measured. A major effort in this proposal is invested in the development of unique chemistries to enable this labelling. I specifically address three types of genomic variation: Variations in genomic layout (including DNA repeats, structural and copy number variations), variations in the patterns of chemical DNA modifications (such as methylation of cytosine bases) and variations in the chromatin composition (including nucleosome and transcription factor distributions). I will use physical extension of long DNA molecules on surfaces and in nanofluidic channels to reveal this information visually in the form of a linear, fluorescent “barcode” that is read-out by advanced imaging techniques. Similarly, DNA molecules will be threaded through a nanopore where the sequential position of “bulky” molecular groups attached to the DNA may be inferred from temporal modulation of an ionic current measured across the pore.

Keywords: single molecule detection,super-resolution microscopy
Opening Jerusalem Archives: For a connected History of ‘Citadinité’ in the Holy City (1840-1940) (OPEN-JERUSALEM)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: The study of the human past
Countries involved: France
Call:  (ERC-2013-StG, 2013)
Start date: 2014-02-01
End date: 2019-01-31
Duration (months): 60.0
Total project cost (EUR): 1442300.8
EU funding (EUR): 1442300.8
Participants: 1
Project status: CLOSED

Jerusalem is undoubtedly one of the cities that receives the most attention from historians, but the available bibliography is plagued, generally speaking, by three major flaws. First, most studies are devoted either to ancient and medieval history, or to the very recent history of the city (after the 1948 War). The Ottoman period (1517-1917) and the British Mandate (1917-1947) are decidedly less studied, as though only the Bible, the Crusades, and then the Israeli-Palestinian conflict were worthy of interest. Second, the overwhelming majority of existing studies focus on religious and geopolitical aspects of the city’s history and thus Jerusalem appears either as a jumble of shrines or as a battlefield. The third flaw is the cause of the other two: most Jerusalem historians limit their studies to the history of only one community of the Holy City, thus contributing to the creation of a segmented historical narrative that precludes a more sweeping view of the city. The history of Jerusalem, which is doubtlessly the epitome of the “global city” and should consequently benefit from recent historiographic advances in “connected history”, instead remains one of the most fragmented histories anywhere. As a consequence, the 'citadinité' (“urban citizenship”) shared by the inhabitants of Jerusalem from 1840’s Ottoman’s Reforms to 1940’s War is invisible in the bibliography. Yet truly decompartmentalizing Jersualem’s historiographies means finding ways of interconnecting its archives, a central idea in this project. Supported by an European institution reputed for its stability, this project will distinguish itself through the scientific quality of its research tools and the close attention it pays to local administrative archives. Last but not least, it will not limit itself to a logistical initiative but will scientifically utilize those sources as part of a real intellectual proposal intended to produce a connected history of citadinité in Jerusalem from 1840 to 1940.