Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : RiboInflam (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 1499720.0 €

Inflammation is a highly regulated process that acts as a first line of defense against pathogens infections. Triggered by cellular pattern recognition receptors (PRRs) that recognize specific microbial components and endogenous or exogenous non-microbial components, activation of inflammation induces a dynamic and coordinated gene expression program that leads to the production of cytokines and chemokines to attract effector cells to the site of infection. Although a robust inflammatory response is required for efficient clearance of pathogens, uncontrolled or prolonged inflammation can lead to inflammatory disorders such as septic shocks or to autoimmune diseases like lupus. Most studies have focused so far on the transcriptional control of the inflammatory gene expression program. However, post-transcriptional regulatory mechanisms involving mRNA splicing, mRNA decay or translation have also been described to control the inflammatory response. Among these, regulation of mRNA translation allows for rapid and reversible modulation of gene expression but its precise role and control mechanisms in the inflammatory response remain poorly understood. Using innovative technologies, our project aims at characterizing the role of ribosomes and mRNA translation in regulating the inflammatory response. In particular, we propose to identify the complete set of of ribosome accessory proteins and to determine their role in the context of “specialized ribosomes” with specific regulatory activities. We will also study the cross-talks between ribosomes and other cellular processes such as mRNA decay and uncover the role of mRNA editing in regulating translation during the inflammatory response. From this work, we expect to identify new regulatory mechanisms that orchestrate inflammation as well as cellular factors that could represent new therapeutic targets for the design of drugs modulating inflammation.

Mots-clés : inflammation,macrophage,innate immunity,ribosome,translation
Projet ERC : CMIL (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Austrian Academy of Sciences — Pays : Autriche — Rôle : PI
Acronyme de l'entité : OAW
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 1701011.0 €

Inflammation is a response to noxious stimuli and initiates tissue repair. If resolution fails, however, chronic inflammation develops, which drives tissue damage in many diseases including autoimmunity, cancer and infections. Inflammatory processes are increasingly being appreciated as tightly integrated with metabolic pathways. The molecular crosstalk occurs on different levels including secreted metabolites and cytokines. I hypothesise that this interface of metabolism and inflammation represents a functional rheostat that shapes tissue damage and disease. Here, I propose to analyse the metabolic and inflammatory processes in a mouse model of chronic viral hepatitis. I chose this model to explore the inflammatory rheostat because the liver is the central organ for metabolism and a hotspot for receiving, processing and distributing local and systemic signals. Cutting-edge technologies including deep sequencing, quantitative proteomics and metabolomics will let us create longitudinal multi-dimensional maps of virus-induced alterations. Paired with immunological, virological and pathological analyses, I expect to identify novel regulatory nodes between metabolism and inflammation. Within our systems-wide experiments and supported by preliminary results, we will specifically focus on the immunomodulatory roles of the metabolite bile acids and oxidative metabolism. These as well as other candidates will be investigated by genetic and pharmacological perturbations in cell culture and in mouse models. Bioinformatics integration of the orthogonal profiling kinetics is expected to reveal novel properties of the molecular networks mediating between metabolism and inflammation. This proposed cross-disciplinary approach aims to improve our understanding of the crosstalk of metabolism and inflammation. The results of this project may be relevant to viral hepatitis in man and bear broader implications for other inflammatory diseases.

Mots-clés : chronic viral infection,hepatitis,lymphocytic choriomeningitis virus,lcmv,inflammation,liver,metabolism,metabolites,interferon,bile acids,crosstalk,systems biology
Projet ERC : REpAIR (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Universität Hamburg — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : UHH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1356125.0 €

Inflammation is fundamental to promote tissue regeneration upon injury, and in turn, the resolution of the immune response. Physiological tissue regeneration depends on fine-tuned interaction between the immune system, the tissue, and the microbiota. However, the complex communication between these three components and the molecules that mediate it are unclear. Understanding this is fundamental to prevent immune-mediated diseases and even cancer. This is particularly important at mucosal surfaces, where continued regeneration occurs. Therefore, we hypothesize that inflammatory bowel disease (IBD) and colorectal cancer (CRC) are a consequence of a miscommunication between these components. Interleukin-22 (IL-22) is one key orchestrator of this communication: It is produced by immune cells and by acting on intestinal epithelial cells, it modulates the composition of the microbiota and promotes tissue regeneration. However, IL-22 can also promote both chronic inflammation and cancer. Exactly what regulates these paradoxical effects remains unclear. Of note, there is an endogenous inhibitor of IL-22, namely IL-22 binding protein (IL-22BP), which blocks IL-22 activity. We hypothesize that a misguided spatio-temporal regulation of the IL-22 – IL-22BP axis is the cause of pathogenic effects of IL-22. In particular, we will analyse: (i) the location, and the functional and molecular heterogeneity; (ii) the origin and fate of IL-22 and IL-22BP producing immune cells; and (iii) the role of the microbiota in regulating them. To this end, we will use new transgenic and gnotobiotic mouse models, single cell RNA sequencing and human samples. In short, by studying the IL-22 - IL-22BP axis, we will understand how the complex interactions between the immune system, the tissue, and the microbiota lead to either physiological or pathological tissue regeneration. This will provide the basis for therapies controlling inflammation and tissue regeneration in a spatio-temporal manner.

Mots-clés : inflammatory bowel disease,colorectal cancer,t cells,microbiota,cytokines,tissue regeneration
Projet ERC : INSTRUCT (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 443348.65 €

Information flows are fundamental to how well markets work for consumers and firms. Consumers get different deals depending on (a) how much they know about the offerings of different firms and, conversely, (b) how much firms know about consumer preferences. The internet is transforming both (a) and (b), allowing consuInformation flows are fundamental to how well markets work for consumers and firms. Consumers get different deals depending on (a) how much they know about the offerings of different firms and, conversely, (b) how much firms know about consumer preferences. The internet is transforming both (a) and (b), allowing consumers to discover and evaluate products with greater ease and enabling firms to personalise prices and target their advertising. Economic understanding currently lags behind what is needed for robust policy formulation in the areas of consumer privacy, price discrimination, and the costs of search and advertising. This project aims to fill that gap. How does the structure of information in consumer markets affect market performance, and which kinds of information should be stimulated or controlled? I propose four lines of enquiry to address this over-arching theme: (1) to develop innovative modeling techniques to understand how the structure of information about consumer preferences (possessed by firms and by consumers themselves) affects overall surplus and how that surplus is divided between firms and consumers; (2) to develop methods to study how the structure of consideration sets (i.e., the set of firms a consumer is able or willing to consider for her purchase) affects market outcomes; (3) to analyse how the information channels of advertising by firms and search by consumers interact and which is more important for the efficient functioning of markets, and (4) to investigate which aspects of their preferences consumers are willing to share with firms and thereby understand better how to solve difficult but important pricing problems.
Projet ERC : UNMOVED (Horizon 2020, appel 2014, Proof of concept grants)
Entité participante : Technion – Israel Institute of Technology — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Information in the nervous system is typically represented in activity patterns distributed across large populations of neurons in three dimensions, and there is a lot of current interest in the development of systems that can volumetrically image these patterns (or other distributed processes) in real-time. During our work towards imaging responses to artificial retinal stimulation we have developed a solution for remotely manipulating the illumination plane during temporal-focusing multiphoton imaging (a powerful bio-microscopy and photo-manipulation modality). This technique and its variations could provide unprecedented access into rapid 3D imaging at an exciting time for the neuroimaging field, where major initiatives for high-resolution brain activity mapping have been launched, and could potentially also be applied towards innovative approaches to micro-endoscopy and other applications.
Projet ERC : WIDE (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : École des hautes études commerciales de Paris — Pays : France — Rôle : PI
Acronyme de l'entité : HEC Paris
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1240922.0 €

Informational frictions lead to inefficient allocations, reducing welfare. Dynamic incentive theory offers a powerful conceptual framework to analyse the optimal design of contracts and mechanisms mitigating these inefficiencies. Its technical difficulty and abstractness, however, have limited its applications. The objective of this project is to develop new frameworks to enhance the applicability of dynamic incentive theory and address important unanswered applied questions: 1) In corporate finance, I will evaluate the quantitative relevance of dynamic contract theory. To do so, I will develop a new structural econometric framework and estimate the magnitude of dynamic incentive problems and their consequences for corporate investment and bankruptcy risk. 2) In organization theory, I will study if equilibrium choices lead to excessive complexity. I will model the link between complexity and incentives. Then, in contrast with standard dynamic contract theory, which takes the tasks of agents as given, I will endogenize agents’ tasks and their complexity. Finally I will confront this theory to new data on complexity. 3) In asset pricing, I will build a novel equilibrium framework to study the consequences of dynamic incentive constraints for relative prices and the cross section of expected returns. In addition to this positive analysis, I will delineate the normative implications of the theory for financial markets regulation. 4) In public finance, I will study whether financial transactions should be taxed. To do so, I will extend the dynamic mechanism design paradigm of “new public finance” to financial transaction taxes and compare the distortions induced by these taxes with those induced by taxes on capital or labour income. By delivering useful results on four important issues, this project will demonstrate the applicability of dynamic incentive theory. To do so it will develop novel tools by combining dynamic incentive theory with other methodologies.

Mots-clés : dynamic financial contracting,asset pricing under limited commitment,incentives,financial transactions tax,structural econometrics of corporate finance
Projet ERC : IRIS (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : UK Research and Innovation — Pays : Royaume-Uni — Rôle : Partner
Acronyme de l'entité : UKRI
Type d'entité : Recherche
Financement ERC de l'entité : 199951.0 €

Infrared sensing technology has a central role to play in addressing 21st century global challenges in healthcare, security and environmental sensing. Promising new applications hinge on the ability to detect individual quanta of light: single photons. At infrared wavelengths this is a formidable task due to the low photon energy, and commercial-off-the-shelf technologies fall far short of the required performance. IRIS will engineer revolutionary photon counting infrared imaging and sensing solutions, with unprecedented spectral range, efficiency, timing resolution and low noise. Using state-of-the-art materials and nanofabrication techniques, novel superconducting detector technology will be scaled up from single pixels to large area photon counting arrays. Efficient readout and optical coupling solutions will be developed and implemented. IRIS will exploit space age cryogenic technology to create compact and mobile detector systems. IRIS will deploy these systems for the first time in revolutionary infrared imaging and sensing applications: dosimetry for laser based cancer treatment, atmospheric remote sensing of greenhouse gases and real-time distributed fibre sensing for geothermal energy.

Mots-clés : infrared detector,remote sensing,superconducting detector,superconducting device,photon counting,single photon detection
Projet ERC : GV-FLU (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Tel Aviv University — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1497000.0 €

Inherited variation in the quantity and functionality of immune cells plays a key role in determining phenotypic diversity between individuals. Surprisingly little is known, however, about the specific contribution of immune cell subsets to variation in phenotypes such as susceptibility to infectious diseases and the underlying genetic variation. In many complex diseases, we currently have a poor understanding of the driver cell types that are responsible for inherited variation in disease states. A comprehensive mapping of quantities and functions of immune cell types during the course of disease, in large cohorts, bears the potential to transform genetic research; provides understanding of the genetic and immune basis of phenotypes; and reveals the key driver cell subsets. Here I aim to derive a mechanistic understanding of how variation in quantity and function of immune cell subsets mediates inherited variation in disease states. I propose to develop a computational model that integrates predicted quantities and functions of cell subsets with genotypic and phenotypic information, leading to specific hypotheses on physiological regulation and the particular cell subsets that drive phenotypic diversity. To circumvent the technical difficulty in quantifying a large number of immune cell types, I will profile gene expression and computationally quantify changes in a large number of cell types. I will develop and apply this strategy to dissect Influenza infection in mice. Since changes in immune responses play a key role in complex diseases, our ability to predict variation in immune responses from genotypes would have important clinical implications. This project has far reaching implications as the paradigm developed here will transform quantitative genetics studies as well as systems immunology research of complex disease. This approach will be applicable to any mammalian disease, allowing researchers to dissect their own systems at unprecedented detail.

Mots-clés : complex traits,quantitative genetics,immune response,network reconstruction,computational,biology,influenza infection
Projet ERC : DEVBRAINTRAIN (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Inhibitory control refers to the ability to control behavioural impulses and is critical for cognitive development. It has been traditionally thought of as a stable trait across the lifespan but recent insights from cognitive neuroscience show prolonged changes in brain regions that support inhibitory control indicating greater malleability than previously believed. Because childhood inhibitory control predicts well-being later in life this suggests exciting opportunities for enhancing inhibitory control. I build on highly promising pilot results and draw on a recent neurocognitive model of inhibitory control to test 1) if inhibitory control can be enhanced during childhood, 2) if this transfers onto other domains important for healthy psychological development such as prosocial- and patient decision-making and academic achievement and 3) which factors predict training success. Children aged 5 to 10 years will undergo 8 weeks of inhibitory control training, which is a critical duration for observing prolonged training effects and be compared to a group undergoing active sham-training of comparable stimuli and duration but without inhibition. I will assess training effects on the brain and look at transfer effects onto other domains such as other executive functions, prosocial- and patient decision-making and academic achievement, both immediately and 1 year after training. I expect training to 1) improve inhibitory control, 2) transfer onto performance on above-mentioned domains and 3) elicit neural changes indicating the effectiveness of training for re- and proactive control. I also expect that individual differences in inhibitory control ability and associated brain regions prior to training will predict training success. The proposed research has the potential to generate a new and ground-breaking framework on early malleability of inhibitory control with implications for interventions at the time point of greatest likely impact.

Mots-clés : child development,inhibitory control,training and transfer effects
Projet ERC : P450RESIST (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : UK Research and Innovation — Pays : Royaume-Uni — Rôle : Partner
Acronyme de l'entité : UKRI
Type d'entité : Recherche
Financement ERC de l'entité : 26017.5 €

Insect resistance to synthetic insecticides and the anti-herbivore defence chemicals produced by many plants is an ongoing challenge to sustainable pest management while also an exceptional model system to study adaptive evolution. The cytochrome P450s are a superfamily of enzymes that are ubiquitous in nature, and one of the most important enzyme families used by insects to defend themselves against natural and synthetic xenobiotics. Insects have been shown to evolve resistance through quantitative changes in P450 expression or via qualitative changes in P450s that alter metabolic activity. Despite their importance in conferring resistance the variety of regulatory changes that modulate P450 expression in resistant insects and their relative frequency/impact is not fully understood. Furthermore, although qualitative changes in insect P450s associated with resistance are relatively rare they represent a unique opportunity to characterise insecticide/toxin binding and identify the critical structure/function determinants of the P450/insect toxin interaction. In this project I will exploit cutting-edge advances in genomics, epigenetics and transgenics to study the insect P450 resistome in three main workpackages: WP-1: Will identify the molecular drivers of quantitative changes to insect P450s. WP-2: Will explore the role of qualitative changes in insect P450s in mediating resistance and identify structure/function determinants of insecticide metabolism. WP-3: Will exploit the knowledge gained in WP1/2 and from previous research to deliver a ‘P450 toolkit’ consisting of in vitro and in vivo screening tools, with which to identify resistance breaking chemistry, and high-throughput diagnostics for use in resistance management. In summary this project will provide novel insights into this important enzyme family and provide tools that can be used to develop new products and strategies that slow, prevent, or overcome resistance and so ensure sustainable crop protection

Mots-clés : insect resistance to xenobiotics,insecticide resistance,detoxification enzymes,rapid adaptation