Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : HeaLS (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Soci al World and Its Interactions
Entité participante : Institut nordique pour les études sur l’innovation, la recherche et l’éducation — Pays : Norvège — Rôle : Partner
Acronyme de l'entité : NIFU
Type d'entité : Recherche
Financement ERC de l'entité : 350000.0 €

Mental illness is a major health burden worldwide and the health problems with the heaviest financial burden in Norway. Half of chronic mental disorders emerge before the age of 14, and mental health problems in youth are increasing. The Norwegian government has implemented the interdisciplinary topic "Health and life skills" (HLS) in primary and secondary education to provide pupils with competences to promote health and self-efficacy. School-based interventions may improve mental health and academic performance, but their effects depend on the quality of implementation. There are large variations in how HLS is implemented within and across schools due to lack of national guidelines and a reliance on teachers’ professional judgement. Delayed implementation for some grades and longitudinal nationwide registry linkages forms a natural experiment and rare opportunity to investigate the impact of diverse implementation methods of a politically determined, long-term and population-wide measure. The aim of this interdisciplinary study is to evaluate how variations in the implementation of HLS relate to the intervention’s effect on pupils' mental health, quality of life, school environment, academic performance and dropout. We will collect new HLS implementation data from 5,000 teachers/employees, 1,000 school principals and 180 school owners. Information from these key samples will be combined with prior linked data for 750 000 pupils from existing national registries and large surveys, including educational, health and background information.  The research group includes researchers specialized in education, mental and public health, health promotion, classroom research, school surveys, register-based studies and advanced multi-level methods. The evaluation may affect further implementation and practice of HLS nationally and globally, and thereby promote pupils’ mental health and academic performance and thus also their future.

Mots-clés : curricular changes implementation mental health socio emotional school environment
Projet ERC : artFibro (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Alexander Fleming Biomedical Sciences Research Center — Pays : Grèce — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1997250.0 €

Lung cancer is the leading cause of cancer death. Immunotherapy improved survival rates, but efficacy is limited to selected patients. We recently discovered universal antigen presenting fibroblasts (apFibros) across human and murine lung tumors and showed that they directly stimulate cancer-specific CD4 T cells, creating immunological hot spots that support immune rejection. These studies achieved a breakthrough on the role of in situ cancer antigen presentation and proposed a novel model whereby tumors can sustain T cells independently of lymph nodes. Preliminary data suggest that lung apFibros help overcome resistance to checkpoint inhibitors. For their immunotherapeutic exploitation of apFibros two bottlenecks must be overcome: low numbers and incomplete understanding of their configurations. We will integrate computational and laboratory experiments and work in parallel in human and mouse models to generate perturbation datasets across single-cell/cell systems, transcriptomics/epigenomics, spatial/temporal levels, and dissect the molecular landscape that regulates fibroblast states. Our ultimate goal is to unravel perturbations that can diverge cancer-associated fibroblasts to antigen presenting states.  The following questions are at the core of our proposal i) how do diverse fibroblast states emerge and evolve? ii) which gene regulatory networks drive specificity of these states? ii) which are the functional modules that are driven by apFibros and how are they mechanistically explained? iv) how can we transdifferentiate existing fibroblasts to acquire antigen presenting states? v) how can fibroblast reprogramming help overcome immunotherapy resistance?  The proposed research should help advance mechanistic concepts in what we term the “adaptive immune mesenchyme”, decode the complexity of peripheral antigen presentation in tumors and beyond and promote targeting of the stroma for immunotherapy.

Mots-clés : fibroblasts,mesenchyme,cancer antigens,transdifferentiation,cell reprogramming,immunotherapy,in vivo gene editing
Projet ERC : INSUREADAPT (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Human Mobility, Environment, and Space
Entité participante : Université libre d'Amsterdam — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999999.0 €

Natural disasters cause substantial economic losses, which are expected to increase due to climate change. The insurance sector plays a central role in managing these risks. It is thus imperative that insurers accurately assess and address climate risks. Risk assessment methods currently fall short in accurately understanding climate risks because they focus on single hazards (e.g. floods) instead of correlated multi-hazard risks (e.g. windstorms and floods) affected by climate change. They also insufficiently account for human climate adaptation processes leading to risk reduction, which are characterized by bounded rationality and social interaction. Furthermore, additional insights are needed into how to design insurance arrangements that address climate change and stimulate policyholders to adapt to multi-hazard climate risks by limiting natural disaster damage.  This project aims to design insurance arrangements to enhance policyholders’ adaptation to multi-hazard climate risks by combining financial coverage with comprehensive strategies for stimulating risk reduction. Its interdisciplinary approach goes beyond the state-of-the-art by creating novel multi-hazard climate risk assessments for insurance and by developing agent-based models (ABMs) that account for boundedly rational human adaptation decisions and social interaction. The ABMs evaluate natural disaster insurance arrangements for EU countries with diverse risk contexts and assess strategies for stimulating adaptation by policyholders, based on input from behavioural economic studies. Repeated and real-time surveys and economic experiments will identify comprehensive strategies for triggering behavioural change to stimulate adaptation to the multitude of climate change risks individuals face. These strategies linked to (public–private) insurance combine communication on risk and risk reduction measures, insurance incentives (e.g. deductibles, premium discounts), and nudges.

Mots-clés : decision making under climate risk,climate adaptation,climate economics,natural disaster insurance,natural disaster risk assessment
Projet ERC : DecipherAD (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Amsterdam University Medical Centers — Pays : Pays-Bas — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2548734.0 €

Worldwide, 50 million people suffer from dementia, which is caused by Alzheimer’s disease (AD) in 70% of the cases. There is no treatment to stop, reverse or prevent AD. AD is pathologically defined by amyloid plaques and tau tangles in the brain, implying that it is a single disease entity. Still, patients vary greatly in rate of decline and underlying pathophysiology, which hampers the search for cures. I have discovered and replicated 5 AD subtypes in patients based on cerebrospinal fluid proteomics (CSF). Subtypes had distinct pathophysiology, including differences in amyloid metabolism and clearance, as well as in cognitive decline. This indicates that they would need tailored treatments.  The goal of this project is to understand AD subtype specific mechanisms, and how these are related to cognitive decline, taking CSF proteomics as a starting point. I will address the following scientific needs: 1. Understand which AD subtype molecular processes change over time, and how those changes relate to cognitive decline. This requires large datasets of individuals with repeated CSF proteomics. I have access to two large, deeply phenotyped cohorts with already collected repeated CSF samples over 5 years from 700 individuals, in which I will measure proteomics. 2. Study drivers of AD subtypes with genetics and in a subset of n=50 with tissue proteomics. 3. Develop markers in blood for subtype detection, which would remove barriers for clinical use. 4. Test if AD subtypes differently respond to amyloid modifying drugs, which is the strongest proof that AD subtypes need tailored therapy.  If successful, DecipherAD will provide proof of concept that AD subtypes have use as a theragnostic tool, show which genetic factors drive molecular subtypes, how molecular signatures change over time and how these changes relate to cognitive decline, with tools in blood to facilitate implementation in clinical practice. This will catalyse AD subtype tailored treatment development.

Mots-clés : alzheimer s disease,heterogeneity,cerebrospinal fluid proteomics,disease mechanisms
Projet ERC : Learn4DChromosome (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed Matter Physics
Entité participante : Université libre d'Amsterdam — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

The physical organization of bacterial chromosomes is inherently variable, with large conformational fluctuations both from cell to cell and over time. Yet, chromosomes must also be structured to facilitate processes such as transcription, replication, and segregation. A physical description of this dynamic statistical folding of bacterial chromosomes remains largely elusive. Hi-C experiments probe chromosome organization by measuring average contact frequencies of chromosomal loci pairs. Despite the rapidly expanding database of high-resolution Hi-C data for many bacterial species and conditions, these data are still mainly interpreted on a case-by-case basis and with qualitative or heuristic methods. My goal is to develop a principled unifying approach to infer and analyze the dynamic organization of chromosomes from bacterial Hi-C data. This data-driven approach aims to unravel the dynamic statistical folding of chromosomes – and its impact on functional processes – in growing and replicating bacteria. We will infer a bacterial chromosome model from state-of-the-art data using learning methods at the intersection of information theory and statistical mechanics. By combining data-driven with mechanistic modelling approaches, we aim to:  •Decode information contained in Hi-C data by learning both 3D steady-state and 4D dynamic models for the statistical organization of chromosomes. •Provide a unifying statistical mechanics analysis of the dynamic statistical folding of chromosomes across bacterial species under both steady-state and replicating conditions. •Develop theoretical methods using pairwise and multi-contact statistics to study the topology of statistical chromosome folding. My research will advance the field by providing a conceptual understanding of the physical and mechanistic principles that underlie chromosome organization in developing bacteria. This work could shed new light on vital functional processes such as chromosome segregation.

Mots-clés : chromosome organization,physics of bacteria
Projet ERC : H3PMAG (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and Communication Engineering
Entité participante : Université technique du Danemark — Pays : Danemark — Rôle : PI
Acronyme de l'entité : DTU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1998736.0 €

Today’s magnetic components, such as inductors and transformers, in power converters operating at a low frequency of around 100-500 kHz are large compared to other electronic components. These components are a major constraint, limiting the miniaturization and integration of power electronic systems. Increasing the switching frequency can reduce the size of the magnetic components, but this is generally accompanied by significant power losses. I aim to address the fundamental challenges of magnetic components in the frequency range of 1 MHz to 10 MHz, and the main approach will be to reduce the power loss and the component size by creating unique and innovative solutions. My overall objective is to create novel magnetics technologies within conductor materials, nanogranular magnetic materials and component integration that, together with a new winding pattern technique, will enable creation of power converters with unprecedented power-efficiency and power-density. The specific target is to develop efficient, integrated magnetic components suitable for the voltage regulator modules (VRM) in high performance computing systems. I will demonstrate a new VRM converter that is 50 times smaller in size and 5% more efficient than current VRM products. Achieving successful outcomes will have a major impact on the power electronics infrastructure, with the potential to reduce energy waste significantly. To do this, the project’s research questions and hypotheses will be addressed through 5 objectives in 5 corresponding work packages: 1: Mitigation of high-frequency eddy-current winding loss by creating a novel hybrid material structure; 2: Design of new magnetic materials with nanoparticles for a low magnetic core loss; 3: Creation of new core geometries and winding schemes in magnetics integration to handle large current efficiently; 4: “All-in-one” passive components integration mixing the functions of magnetics and capacitors; 5:Experimental verification and demonstration
Projet ERC : REMOTE (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and Processes Engineering
Entité participante : Université technique du Danemark — Pays : Danemark — Rôle : PI
Acronyme de l'entité : DTU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Molecular thermodynamics plays a crucial role in the modeling, design, and optimization of various systems in product and process engineering. Despite significant progress made over the decades, existing thermodynamic models and theories still face significant challenges, particularly when dealing with water and electrolytes. This project seeks to harness these challenges as opportunities to revolutionize molecular thermodynamics by developing novel and physically sound models and theories that surpass current limitations. I aim to deepen our fundamental understanding of the underlying physics and pave the way for a paradigm shift in molecular thermodynamics. By employing a synergistic combination of infrared spectroscopic measurements, quantum chemical calculations, and molecular dynamics simulations, I will go beyond current boundaries and innovate advanced analytical methods to quantify critical structural information that will be used in the development and evaluation of molecular thermodynamic models and theories. I will pioneer the development of a ‘two-state’ theory for association interactions, explicitly accounting for diverse hydrogen-bonding structures characterized by the Gibbs energy of reactions obtained from quantum chemical calculations. We will lead the way in developing a physically consistent theory for ion-ion Coulombic interactions, unlocking the full potential of the molecular thermodynamic models and theories for electrolyte solutions. Extending beyond the established theories, we will develop novel ‘two-state’ theories for generally overlooked properties, such as dielectric constant, surface tension, and electrical conductivity. We will further demonstrate how structural information and these less commonly investigated properties can be systematically employed to evaluate and select the most powerful and physically correct models and theories, moving beyond mere parameterization towards a deeper understanding of molecular thermodynamics.

Mots-clés : molecular thermodynamics,water,electrolytes,two state,infrared spectroscopy,quantum chemical calculations,molecular dynamics simulations,models and theories,physical properties
Projet ERC : APPAC IV (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Université de Turku — Pays : Finlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 808585.0 €

Acute appendicitis is one of the most common surgical emergencies worldwide. For over a century, surgical removal of the appendix has been considered the only treatment option. Landmark trials by our experienced APPAC team have shown that imaging confirmed uncomplicated acute appendicitis is not a surgical emergency defining antibiotics to safe and effective also with only oral antibiotics avoiding unnecessary surgeries resulting in major cost and resource savings. However, the role of antibiotics remains a major knowledge gap. Our pilot APPAC III showed that even symptomatic treatment (placebo) may be sufficient warranting a larger noninferiority trial to assess whether antibiotics are needed in the treatment of uncomplicated acute appendicitis. APPAC IV is a randomized double-blind multicenter clinical trial comparing oral moxifloxacin with placebo in an outpatient setting. APPAC IV aims to evaluate whether antibiotics and hospitalization or both can be omitted in the treatment of uncomplicated appendicitis further significantly increasing cost savings and patient satisfaction; almost 2/3 of all appendectomies (approx. 550.000 operations in Europe), the associated hospital stays, and potentially also antibiotics could be avoided. The growing global health issue of antibiotic resistance threatens effective prevention and treatment of infections. Studies on rational use of antibiotics are warranted and especially in the changing treatment paradigm of such a common disease. The translational MAPPAC II (Microbiology APPAC) substudy includes serum, rectal and fecal samples of the APPAC IV trial patients pre- and post-therapy. The effects of antibiotics on gut microbiota, gut health and correlation to serum cytokines are evaluated in this unique real-life randomized patient cohort. The development of antibiotic resistance and the underlying bacterial defence mechanisms will be evaluated in E. coli and microbiome using microbial single-cell technologies and metagenomics.

Mots-clés : appendicitis uncomplicated acute appendicitis antibiotic therapy symptomatic therapy placebo appendiceal microbiota antibiotic resistance gut microbiota dysbiosis
Projet ERC : HUMANE (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Université de l'est de la Finlande — Pays : Finlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1998389.0 €

The molecular mechanisms leading to Alzheimer's disease (AD) are poorly understood. This is due to lack of human tissue samples for research representing early changes of AD pathology. The accumulating pathology, including beta-amyloid and tau proteins, are manifested by concomitant neuroinflammatory reactions geared by malfunctional microglia. Microglia in the human and mouse AD brain exist in various subpopulations from which a specific, disease-associated microglia population is thought to be involved in AD pathogenesis. However, there is no evidence on whether and how these specific microglial subpopulations actually impair neuronal functions in human AD brain. I will now assess neuron-glia network activities and functions indicative of early AD pathology in humans. I hypothesize that early AD pathology selectively impairs neuronal circuits and that glial cells, especially specific microglia subpopulations, contribute to neuronal dysfunction and cognitive decline. These events contribute to a detectable vesicle-based biomarker profile in cerebrospinal fluid and blood prior the clinical disease. Due to early AD pathology present in a subpopulation of idiopathic normal pressure hydrocephalus (iNPH) patients, the brains of the iNPH patients offer a unique window to evaluate cellular and molecular events occurring during early AD. I combine a series of state-of-the art techniques to answer how and what glial cell subpopulations are associated with altered neuronal network activities at subcellular and spatial resolution in human brain impacted by early AD-related pathology. Novel methodologies established in my lab, knowhow and access to unique brain samples make me uniquely positioned to form a holistic view on how early AD-pathology impacts cellular functions at multiple levels. This will pinpoint novel molecular targets for further validation and new fluid biomarkers.
Projet ERC : E-VOLUTION (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
Entité participante : Université technique de Munich — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1997993.0 €

Global climate and energy challenges require efficient, robust and scalable catalysts for the conversion of renewable energies. Nature has evolved extremely active catalysts (enzymes) for the conversion of small molecules relevant to energy (H2, CO2, N2). The scalability of these enzymes offers distinct advantages over the rare, precious metals that are currently used in energy conversion. Unfortunately, the enzymes are unable to tolerate the extreme conditions of operating fuel cells or electrolyzers. Directed evolution is a powerful approach for improving enzymes, but is mostly restricted to natural amino acids and biological conditions, with limited compatibility for evolving enzymes toward enhanced resistance in abiotic systems. Here, I aim to establish directed evolution in fully abiotic systems, using artificial amino acids to make artificial enzymes that are stable even in extreme conditions. Towards this, I will establish new electrochemical peptide synthesis platforms to enable the generation of enzyme-length peptides using both natural and artificial amino acids. Extended libraries of artificial enzyme variants will be produced and screened directly on electrode microarrays. Top enzyme candidates for the conversion of H2 will be selected using fuel cell/electrolyzer conditions as the evolutionary criteria. By the end, I will have a new procedure for synthesizing libraries of full-length artificial proteins, enabling the creation of thousands of enzyme variants using artificial building blocks. The generation of high-quality datasets will be transformative to drive future machine learning-based evolution steps for both full size enzymes and small-molecule catalysts with applications beyond H2 evolution. We will have discovered highly active catalysts able to sustain conditions of large-scale energy conversion devices, accelerating breakthroughs toward the economically competitive use of renewable energies for fuel and chemical production.

Mots-clés : redox activation,peptide synthesis,redox hydrogels,electrochemical microarray,high throughput screening,directed evolution,energy conversion,catalyst discovery