Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : IMBIBE (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1992578.0 €

The human gut is host to over 100 trillion bacteria that are known to be essential for human health. Intestinal microbes can affect the function of the gastrointestinal (GI) tract, via immunity, nutrient absorption, energy metabolism and intestinal barrier function. Alterations in the microbiome have been linked with many disease phenotypes including colorectal cancer, Crohn’s disease, obesity, diabetes as well as neuropathologies such as autism spectrum disorder (ASD), stress and anxiety. Animal studies remain one of the sole means of assessing the importance of microbiota on development and well-being, however the use of animals to study human systems is increasingly questioned due to ethics, cost and relevance concerns. In vitro models have developed at an accelerated pace in the past decade, benefitting from advances in cell culture (in particular 3D cell culture and use of human cell types), increasing the viability of these systems as alternatives to traditional cell culture methods. This in turn will allow refinement and replacement of animal use. In particular in basic science, or high throughput approaches where animal models are under significant pressure to be replaced, in vitro human models can be singularly appropriate. The development of in vitro models with microbiota has not yet been demonstrated even though the transformative role of the microbiota appears unquestionable. The IMBIBE project will focus on using engineering and materials science approaches to develop complete (i.e. human and microbe) in vitro models to truly capture the human situation. IMBIBE will benefit from cutting edge organic electronic technology which will allow real-time monitoring thus enabling iterative improvements in the models employed. The result from this project will be a platform to study host-microbiome interactions and consequences for pathophysiology, in particular, of the GI tract and brain.

Mots-clés : organic bioelectronics,3d tissue engineering,microbiome,gut brain axis,electrophysiology,in vitro models
Projet ERC : BloodVariome (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Lund University — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

The human hematopoietic system is a paradigmatic, stem cell-maintained organ with enormous cell turnover. Hundreds of billions of new blood cells are produced each day. The process is tightly regulated, and susceptible to perturbation due to genetic variation. In this project, we will explore an innovative, population-genetic approach to find regulators of blood cell formation. Unlike traditional studies on hematopoiesis in vitro or in animal models, we will exploit natural genetic variation to identify DNA sequence variants and genes that influence blood cell formation in vivo in humans. Instead of inserting artificial mutations in mice, we will read out ripples from the experiments that nature has performed during evolution. Building on our previous work, unique population-based materials, mathematical modeling, and the latest genomics and genome editing techniques, we will: 1. Develop high-resolution association data and analysis methods to find DNA sequence variants influencing human hematopoiesis, including stem- and progenitor stages. 2. Identify sequence variants and genes influencing specific stages of adult and fetal/perinatal hematopoiesis. 3. Define the function, and disease associations, of identified variants and genes. Led by the applicant, the project will involve researchers at Lund University, Royal Institute of Technology and deCODE Genetics, and will be carried out in strong environments. It has been preceded by significant preparatory work. It will provide a first detailed analysis of how genetic variation influences human hematopoiesis, potentially increasing our understanding, and abilities to control, diseases marked by abnormal blood cell formation (e.g., leukemia).
Projet ERC : iMPACT (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : National Institute for Nuclear Physics — Pays : Italie — Rôle : Partner
Acronyme de l'entité : INFN
Type d'entité : Recherche
Financement ERC de l'entité : 1035000.0 €

The iMPACT project focuses on the realization of a proton Computed Tomography (pCT) scanner capable of acquiring a target full 3D image with 1s exposure, therefore opening the way to the practical application of proton imaging technique in medical radiotherapy treatments. Such cutting-edge particles scanner combines innovative ideas devised for the future High Energy Physics experiments together with original developments in the microelectronic field to enable charged particles imaging at the GHz scale. In recent years the use of hadrons (1H and 12C ions) for cancer radiation treatment has become an established technique and many facilities are currently operational or under construction worldwide. To fully exploit the therapeutic advantages offered by hadron therapy, precise target (body) imaging for accurate beam delivery is decisive. pCT systems, currently in their R&D phase, provide the ultimate in low dose (< 2 mGy), 3D imaging for hadrons treatment guidance. Key components of a pCT system are the detectors used to track the protons and measure their residual energy. The iMPACT scanner, composed by a proprietary monolithic pixels tracking detector and an innovative achromatic calorimeter, will improve current pCT imaging speed by more than a factor 100, leading to potential recording times of about 1 second for a full 3D target image (compared to present ≈ 10 minutes). The iMPACT detector will also have higher spatial resolution (equal or better than 10 µm) and lower material budget (by a factor 10) respect to state of the art systems, further enhancing 3D imaging accuracy. Not least when considering actual industrial application, production costs will be far lower than existent systems, because all sensors will be designed with commercially available technologies, making it possible to move pCT from the academic research realm to that of viable medical equipment.

Mots-clés : proton tomography,cmos pixel sensors
Projet ERC : Playfields (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : University of Warwick — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149681.0 €

The idea for this Proof of Concept (PoC) is to develop a prototype of a location-based game (LBG) that can be used for teaching fieldwork in a Higher Education (HE) setting. The rationale behind it is that location-based games, understood here as pervasive games in which gameplay develops through a player's mobile location, are promising educational tools for fieldwork, as they: - Are close to student’s lifestyle as digital natives - Offer innovative and creative technologies for using methods in vivo. - Offers educators possibilities to monitor and supervise students’ progress - Allow for different interactions between students, teachers and learning environments - Allow for more creative learning processes for understanding environments and people - Offer accessible and informal ways to break down barriers between researcher and “researched” The game we envisage to prototype will consist of an OpenStreetMap based GPS enabled mobile phone app that can be used by students while conducting fieldwork. The game mixes spatial and qualitative approaches, that prompt students to complete certain educational tasks, plan routes , create narratives, or “claim” certain spots or areas. The app will then feed data created by the students (GPS check-ins, images, texts, recordings) back to a main computer where the findings and activities are collected, scored with points and evaluated by the teachers of the course. Through this central interface organisers of the course as well as BOTs (automated tasks/non-playable entities in the game-world) can send messages, advise and tasks to the participants, information that is also used to share and evaluate the results with students in the classroom. Likewise students can communicate with their supervisors while in the field through this central interface to ask for advise.

Mots-clés : serious games,games for education
Projet ERC : APRA (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2012136.0 €

The idea of mechanical actuator based on intrinsic material properties of liquid-crystalline elastomers (rather than complex engineering of interacting components) has been understood for 20+ years. The remarkable characteristics of LCE actuation (fully reversible action; large-amplitude, with a stroke of 5%-300%; stress-strain-speed response almost exactly matching the human muscle) make it highly attractive in biomedical engineering, robotics, smart textiles, and other fields. Yet, there is a profound difficulty (bottleneck), which remains the reason why this concept has not found its way into any practical devices & applications. LCE actuation requires alignment (monodomain structure) of the local anisotropy in the permanently crosslinked polymer network - which has been impossible to achieve in any useful large-scale configuration except the flat film, due to the unavoidable restrictions of two competing processes: orientational alignment and network crosslinking. Recently, we made a breakthrough, developing LCE vitrimers (polymer networks covalently crosslinked by a bond-exchange reaction). Vitrimers are much more stable than other transient elastomer networks, allow easy thermal re-moulding (making the material fully renewable), and permit molding of complex shapes with intricate local alignment (which are impossible in traditional elastomers). This project will bridge from the concept to technology, tuning the material design for robust nematic LCE vitrimers, imparting photo-actuation capacity with a controlled wavelength, and finally utilising them in practical-engineering actuator applications where the reversible mechanical action is stimulated by light, solvent exposure, or more traditionally - heat. These applications include (but not limited to): continuous spinning light-driven motor, tactile dynamic Braille display, capillary pump and toggle flow switch for microfuidics, active textile fibre, and heliotracking filament that always points at the Sun.
Projet ERC : TOUGHIT (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Montanuniversität Leoben — Pays : Autriche — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1960985.0 €

The ideal structural material should excel in strength and toughness. Strength describes the capability of a defect free component to carry load during operation, while toughness defines the load-bearing capability and ductility in the presence of a crack. For an energy-efficient and safe design, both quantities should be simultaneously high. Unfortunately, they are mutually exclusive, rendering their combination a Holy Grail in materials science. The reason for this incompatibility is rooted in the inverse strength-ductility paradigm. Focussing on metals, the strength is enhanced via microstructure refinement to the nanometer scale, but ductility and damage tolerance simultaneously drop dramatically. Safety-related or highly stressed components are thus made from rather soft metals, indicating tremendous economic impact conceivable. The objective of this project is to design new bulk materials that uniquely combine high strength and toughness. Severe plastic deformation will be employed to create novel nanostructured bulk metals and nanocomposites, utilizing atomistically informed alloy and interface design to promote plastic deformation. The largely unknown nanoscale processes that limit fracture toughness of nanostructured materials will for the first time be directly identified by quantitative nanomechanical fracture experiments performed in-situ in high resolution electron microscopes. Correlation of these unique insights with ab-initio calculations and energy-based elastic-plastic fracture mechanics computations will guide paths for further improvement of the fracture resistance. By combining a versatile synthesis technique with highly advanced in-situ nanomechanical testing permitting unique atomistic-level insights into nanoscale fracture processes and a scale-bridging modelling approach, new mechanism-based strategies to tailor innovative nanostructured metals and composites with unprecedented strength and toughness will be established.
Projet ERC : ThDEFINE (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : European Molecular Biology Laboratory — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : EMBL
Type d'entité : Recherche
Financement ERC de l'entité : 202228.75 €

The immune system consists of a complex continuum of cell types that communicate with each other and non-immune tissues in homeostasis, and during infections, autoimmunity and cancer. Conventional transcriptional and functional profiling enabled by cell surface marker sorting has revealed a great deal about how specific cell types operate en masse, yet important transcriptional heterogeneity that exists within cell populations remains unexplored. High-throughput single cell RNA-seq can overcome this limitation by profiling entire transcriptomes of thousands of individual cells, revealing cell-to-cell variation by decoding patterns within populations masked in bulk transcriptomes. We will exploit this to dissect the mouse CD4+ T cell compartment, a heterogeneous white blood cell population that initiates adaptive immune responses. In AIM 1, we will chart the dynamics of in vivo CD4+ cell states in mouse before, during and after immune response challenges. By sequencing thousands of single cell transcriptomes, we will map the landscape of CD4+ T cell states in an unbiased, quantitative and comprehensive way. In AIM 2, we will predict key transcription factors, cell surface markers, and signalling molecules, including cytokines/chemokines in each cell state through novel computational approaches. Furthermore, our analyses will establish regulatory modules and networks of gene-gene interactions active in immune responses. In AIM 3, we will (a) confirm the in vivo impact of new cell states by performing adoptive cell transfer assays; and (b) validate our predictions of regulatory molecules and interactions using a massively parallel CRISPR/Cas knockout screen in vitro. This powerful integrated approach combines single cell RNA-sequencing, bioinformatics and genetic engineering to dissect CD4+ T cell states, a central compartment of mammalian adaptive immunity, and reveal basic principles of gene regulation.

Mots-clés : single cell genomics,bioinformatics,t helper cells
Projet ERC : REGiREG (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : University Hospital Regensburg — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : UKR
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1522376.36 €

The immune system with its complex interactions of cells and molecules needs a very tight and specific interplay of control elements to ensure the establishment and re-establishment of immune homeostasis after challenges. Regulatory T cells (Tregs) are key-players in this regulatory network. It is now well accepted that deficiency or dysfunction of Tregs causes various severe immune disorders due to immune hyperactivation. Conversely, an increased number of Tregs in tumor-bearing individuals suppresses efficient anti-tumor immunity and, thereby, is often associated with poor prognosis. Cancer immunology is now one of the most exciting and promising frontiers in cancer research, and recent clinical trials have proven that immunotherapies driving to activate T cells can induce durable responses. In this sense, harnessing the potential of Tregs is one of the most promising new approaches to control immune function and to treat cancer. This proposal has two objectives: 1, the identification and characterization of tissue-resident Tregs to principally understand the unique features of Treg specialization in tissues and their function in organ-homeostasis, a phenomenon that is hardly understood, but holds great promise for local, tissue-specific immune intervention. 2, to globally target Tregs, including the lymphoid organ Treg pool, by interfering with their survival and or suppression function. We expect from these studies new basic insights into a fascinating and still arcane aspect of organ-homeostasis as maintained by Tregs, as well as novel small molecule inhibitors and candidate molecules that target Tregs at the systemic level, and eventually at a tissue-specific level.

Mots-clés : regulatory t cells,immune regulation,foxp3,tolerance
Projet ERC : STRUGGLE (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 1909750.0 €

The immune system within each individual host destroys viruses, which manage to escape immunity on the global scale. Recent experiments show population-level responses of both immune repertoires and viruses, and a history dependence of their functional phenotypes. This constrained long-term co-evolution of immune receptor and viral populations is a stochastic many-body problem occurring at many scales, in which the response emerges based on the past states of both the repertoire and viral populations. STRUGGLE infers the details of viral-immune receptor interactions from functional datasets to obtain a predictive statistical model of co-evolution between immune repertoires and viruses. STRUGGLE covers the many scales of immune-virus interactions: from the molecular level, analyzing high-throughput mutational screens of libraries of antibodies binding a given antigen, through the population-level response of immune repertoires, analyzing next-generation sequencing of vaccine-stimulated whole repertoires, to the population level, modeling the long term co-evolution of both repertoires and viruses. STRUGGLE combines a statistical data analysis approach with cross-scale many-body physics to: - build a molecular model for antigen-receptor binding; - learn statistical models for repertoire-level response to viral antigen stimulation; - validate dynamical models of interactions between antigen and immune receptors; - theoretically evaluate the predictive power of the immune system and viruses; - and predict virus strains and immune responses based on past infections. The outcomes of STRUGGLE include the quantitative characterization of the human T-cell response to flu vaccines, with implications for vaccination strategies, and the trout B-cell response to life-threatening rhabdoviruses, which aids vaccine design for fish, with wide use in agriculture. The statistical properties of the co-evolutionary process are needed for informed development of immunotherapies.

Mots-clés : statistical biophysics,evolution,statistical inference,nonlinear dynamical models
Projet ERC : RiboTrace (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Austrian Academy of Sciences — Pays : Autriche — Rôle : Partner
Acronyme de l'entité : OAW
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 550326.5 €

The implementation of distinct gene expression profiles is essential for organismal development, physiological responses to external stimuli or pathogens, and defines a primary cause for human disease. While much attention has been paid to the regulation of transcription, the control over RNA fate and function has only recently emerged as a central hallmark of gene regulation with enormous biological, technological and biomedical implications. Here, we propose to study the molecular principles of RNA silencing, the least understood aspect of post-transcriptional gene regulation. We aim to systematically dissect the mechanisms and biological functions of RNA 3´end uridylation to determine the emerging role of RNA modifications in the regulation of gene expression; we will elucidate fundamental principles of RNA turnover at the genomic scale by time-resolved transcriptomics; and we will use functional genomics and haploid genetics to systematically delineate post-transcriptional gene regulatory pathways. Throughout, we will link our results back to the established function of RNA silencing in the control of organismal development, physiology and disease. Our goal is to acquire fundamental insights into the processes that survey the quality and quantity of the transcriptome to determine possible molecular causes for aberrant RNA levels that have been associated with diverse human diseases. Because of its genetic and biochemical tools, we will use Drosophila melanogaster as a model organism. We will employ a combination of in vivo genetics, cell-free biochemical experiments, bioinformatics, and cell culture methods. What we learn in flies we will test for its conservation in mammalian cell extracts and cultured cells. Overall, we will determine fundamental biological mechanisms of gene regulation trough pathways with enormous biological impact in health and disease.

Mots-clés : rna silencing,rna metabolism,rnp enzymology,rna modifications,rna uridylation,rna decay,post transcriptional gene regulation,time resolved rna profiling