Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : Spatial Proteomics (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Max Delbrück Center — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MDC
Type d'entité : Recherche
Financement ERC de l'entité : 1470851.0 €

Health and disease states result from dynamic cellular interactions within spatially defined regions in tissues and organs. In diseases such as cancer, these interactions are often disturbed, but their systematic analysis with respect to their impact on the proteome, a close proxy for cellular function, has so far remained elusive. To overcome this major bottleneck in molecular biosciences, I propose to develop and apply Deep Spatial Proteomics (DSP), a multimodal strategy, which for the first time will link distinct cellular neighbourhoods within biological samples to functional proteome states. DSP will combine multiplex immunofluorescence imaging and machine-learning driven cellular neighbourhood profiling with single-cell sensitivity mass spectrometry (MS) based proteomics. Our preliminary data support the feasibility and strong potential of DSP to uncover novel disease mechanisms, drug targets and predictive biomarkers. After development and rigorous benchmarking, we will apply DSP to an already available retrospective cohort of advanced head and neck squamous cell carcinoma, where response rates for anti-cancer immunotherapy are only below twenty percent. The correlation of cell states and spatial neighbourhoods with clinical outcomes will allow us to identify cell communities of highest likelihood to be critical for treatment response and hence patient survival. Through their functional characterisation by deep MS based proteomics, we will not only gain unique biological insights into immunotherapy resistance and potential therapeutic targets, but also identify predictive candidate markers to improve patient stratification. This new concept will have strong implications for basic and translational research, far beyond the study of cancer immunotherapy. DSP could pave the way for a plethora of spatial proteomics applications with countless opportunities for discovery-driven biomedical research.

Mots-clés : spatial biology,single cell proteomics,cancer biology,tissue proteomics,digital pathology,multiplex imaging,personalised medicine,biomarker research,shotgun proteomics,cellular neighbourhoods
Projet ERC : ISLANDLAB (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Study of the Human Past
Entité participante : Université de Malte — Pays : Malte — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 190789.24 €

Humans are fragmenting ecosystems into habitat 'islands', causing an unprecedented global collapse of large mammal populations just as science is discovering their essential ecological roles. The impact of these losses is such that our understanding of the contemporary biosphere is clearly shaped by a world artificially depleted of terrestrial giants. However, the causes of megafaunal extinctions over a much deeper, >50,000-year timeframe remain strongly contested. How did specific anthropogenic and/or climate factors interact to transform and collapse megafaunal ecosystems and what implications did this have for human societies at different points in time? The feedbacks and ecological legacies of these older extinctions have important lessons for the current biodiversity crisis, yet the dearth of good quality fossil and contextual data from many regions, settings and species has prevented robust appraisal. ISLANDLAB will explore these questions using the Maltese Islands as a frame of reference for the effects of anthropogenic ecosystem fragmentation. Pilot work has already uncovered an unprecedented deep-time record of pristine natural systems successively interrupted by waves of humans. Direct interaction between humans and the endemic megafauna begins with a likely Neanderthal presence and ends with the first monumental civilizations, with exponential losses and subsequent faunal reintroductions lasting until the mid-Holocene. By building high-resolution ecological, climatic, and archaeological characterisations of Malta before and after human arrival and subsequent alteration of biotas, ISLANDLAB will therefore document long-term legacies and feedbacks between ecological changes, societal responses, and ecosystem resilience. More broadly, the results will shed light on extinction processes in current anthropogenic landscapes, elucidating the ecological and human dimensions of restoration pathways from an island paradigm at a pivot between Europe and Africa.

Mots-clés : human evolution,anthropocene,megafauna
Projet ERC : Earth2Sea (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth System Science
Entité participante : Imperial College London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : ICL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499622.0 €

Nearly 700 million people live along flood-susceptible coastlines and actionable sea-level forecasts are urgently needed to protect these populations and their €4 trillion of critical infrastructure from rising sea levels. Unfortunately, current sea-level projections are of limited use due to deep uncertainties in the ice-sheet model calculations used to produce them. For example, the last Intergovernmental Panel on Climate Change report found end-of-century sea level could reach anywhere from 0.3 to 2 m above present.  Most of this uncertainty relates to ice-sheet instabilities that, once triggered, could lead to rapid sea-level rise. It can be substantially reduced by calibrating model parameterisations of these instabilities so that they reproduce past ice volumes, but the reliability of existing calibrations is challenged by the recent discovery that mantle flow generates much faster changes in Earth’s surface elevation than had been recognised. This paradigm shift in geodynamics implies that: i) accepted estimates of past ice volume may be ~25–50% too high, since the ancient shoreline elevations underpinning them have been uplifted by mantle flow; and ii) existing models are missing key physics, leading them to underestimate modern post-glacial bedrock rebound rates by a factor of ~10 and overestimate ice-sheet instability.  I will solve these issues by integrating new sea-level marker datasets with innovative mantle flow reconstructions to obtain probabilistic and geodynamically corrected estimates of past ice-sheet volume and sensitivity. By calibrating ice-sheet models that are compatible with this revised understanding of the palaeorecord and correctly incorporate mantle–ice-sheet feedbacks, I will produce the first geodynamically accurate global and regional-scale sea-level projections. These groundbreaking forecasts will enable decisionmakers to improve long-term coastal defence plans and better protect human life.

Mots-clés : cryosphere geodynamics palaeoclimate geomorphology mineral physics rock rheology machine learning
Projet ERC : ReThink (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Imperial College London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : ICL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1498999.0 €

All recent viral pandemics originated following human adaptation of zoonotic viruses. Our front-line antiviral defences are a major barrier to these viruses. Specifically, our cells encode antiviral proteins -that can be species-specific-, and directly inhibit viral entry, replication, and spread, thus influencing the outcome of infection. Current dogma states that antiviral proteins induced by interferon signalling, named interferon stimulated genes (ISGs), are the most significant front-line of defence. However, as ISGs are induced upon recognition of an already replicating virus, I hypothesize that an array of proteins that are constitutively expressed act to contain the initial wave of viral infection before the more specific and potent ISGs are expressed, thus providing a critical first-line of defence that influences pathogenesis and interspecies transmission. Supporting this hypothesis, my recent genome-wide multi-OMICs investigation of dengue (DENV) and influenza virus (IAV) restriction revealed that 75% of the proteins that inhibited viral infection are non-ISGs. Integrative analysis of these proteins revealed enrichment in general cellular pathways, -many not previously linked to viral restriction-, with significant enrichment in homeostasis maintenance. Moreover, depletion of one single of these proteins resulted in 100% mortality in infected mice, confirming their role in pathogenesis. Using DENV as a model of emergent WHO-priority virus, I will now characterize how these proteins inhibit DENV and other related (west Nile and zika) and unrelated viruses (IAV) (Objective 1). I will investigate their impact on DENV pathogenesis using attenuated and virulent clinical isolates (Objective 2) and as barriers of interspecies transmission using ex vivo models (Objective 3). Overall, this work will shift our understanding of antiviral defences, opening a new area of research that offers signatures of pathogenesis, surveillance, and broad-acting antiviral targets.

Mots-clés : pandemic viruses,host defences,emergent viruses
Projet ERC : AccessVR (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer Science and Informatics
Entité participante : Helmholtz-Gemeinschaft — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : HGF
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1374771.0 €

AccessVR will fill the gap in the scientific knowledge on how people with physical disability – particularly people with limited upper- and lower body mobility – access and experience Virtual Reality (VR) technology. Many of the several million physically disabled people in the EU cannot tap into the huge potential of the technology for leisure, education, and work: VR systems are commonly designed for non-disabled human bodies, but as a result of the complexity of VR technology, fundamental accessibility barriers for physically disabled users remain unaddressed.  AccessVR addresses this issue through development of an experience-centric framework for accessible VR technology. The framework will build on technology case studies and a modular VR application that address physical and digital access barriers to VR, and will be constructed against disability studies as theoretical backdrop. The first phase of the research will examine preferences and needs of disabled people regarding user interfaces and representation of disability in VR through co-creation of individually tailored VR prototypes. In a second phase, the project will synthesize outcomes into a middleware layer, and develop an adaptive VR platform featuring entertainment and workplace scenarios. In the third phase, the VR platform will be leveraged to evaluate the experience of physically disabled people in VR to refine the framework based on empirical data.  The goal of AccessVR is to further our understanding of how to create engaging VR experiences for people with physical disability that combine the removal of physical, digital, and experiential access barriers. Results are expected to have significant impact on the design of body-centric technology and the inclusion of physically disabled people. Ultimately, AccessVR will enable future research on disability and VR, contribute to the accessible design of the technology, and lay the foundation for more inclusive technological futures.

Mots-clés : virtual reality,accessibility,interaction techniques,input hardware,co creation
Projet ERC : SOLG for Policy (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : Helmholtz-Gemeinschaft — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : HGF
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1483639.0 €

Policy decisions about government borrowing, taxation, and spending have a differential impact on generations and thus imply substantial intergenerational transfers. The costs and benefits of these policies occur over decades and come with large uncertainty, for instance related to productivity growth, global financial conditions, and demographic trends. Therefore, fiscal policies, whether intentional or not, transfer risk and resources across generations. Assessing their impact on welfare calls for simulating such policies in models that include the relevant demographics and risks, yet also the related risk-premia. The latter lower government borrowing costs relative to the expected return on investments and are thus particularly important for the welfare implications of fiscal policy. SOLG for Policy aims to build stochastic overlapping-generations (SOLG) models that integrate all these elements and are thus able to quantitatively assess the welfare implications of fiscal policy choices involving intergenerational redistribution and risk-sharing. To solve these models despite their high-dimensional nature, SOLG for Policy leverages recent advances in computational economics based on adaptive sparse grids (ASGs) and develops three extensions of this approach. First, using shape-preserving ASGs to facilitate value function iteration. Second, merging ASGs with endogenous grids to avoid compute-intensive optimization steps. Third, parameterizing intergenerational distributions to further alleviate the curse of dimensionality. Policy questions that will be addressed include: Should the debt accumulated in the Covid crisis be paid down through taxation or do low real interest rates make it desirable to leave the debt and its uncertain burden for future taxpayers to deal with? Is it feasible and desirable to make the pension system provide less redistribution yet more insurance across generations, and how can this be achieved?
Projet ERC : CHIRALPHONONICS (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed Matter Physics
Entité participante : Université de technologie d'Eindhoven — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

This projects aims to establish a new paradigm in the ultrafast control of solids, by using the angular momentum of chiral lattice vibrations (chiral phonons) to manipulate, induce, and switch electronic phases.  The properties of solids are fundamentally determined by the crystal-lattice geometry. Developments of ultrashort terahertz and mid-IR pulses in the past decade have made it possible to dynamically modify the crystal structure by resonantly driving coherent phonons. These phonons exchange energy and momentum with the electrons, modifying interactions that are dependent on the distance between the atoms.  Chiral phonons, in turn, have mostly been regarded as a dissipation channel for electronic angular momentum and only recently been used for ultrafast control of solids, following seminal theoretical predictions of me and my colleagues. The reason for this is rooted in two challenges: the lack of feasible protocols to coherently excite chiral phonons across the Brillouin zone and the complexity of angular momentum coupling processes out of the equilibrium.  CHIRALPHONONICS will address these challenges by bridging the gap between phonon angular momentum theory and ultrafast dynamical simulations. My team and I will investigate how phonon angular momentum can be coherently generated coupled to electronic, spin, and orbital degrees of freedom that are connected to functional properties, including topological and ferroic order. We will combine microscopic modeling with first-principles calculations to create effective ab-initio informed models that allow us to both predict novel fundamental coupling mechanisms as well as realize quantitative materials implementations.  This research will lead to new functionalities in solids and design principles for quantum materials out of the equilibrium. Pioneering the field of ultrafast chiral phononics will open an avenue towards technologies based on phonon angular momentum switching of electronic states.

Mots-clés : chiral phonons,ultrafast dynamics,quantum materials
Projet ERC : STAPLE (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental Constituents of Matter
Entité participante : Institute of Nuclear Physics, Polish Academy of Sciences — Pays : Pologne — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1022706.0 €

Our understanding of the universe's fundamental building blocks is primarily determined by measurements in earth-based scattering experiments at high energies like those conducted at the Large Hadron Collider (LHC). The precise comparison between measured scattering cross-sections and first-principle theory predictions allows us to distinguish and constrain different models of microscopic physics. This strategy led to the Standard Model of Particle Physics (SM).  Despite the SM's success, there remain open questions related to particle physics: the matter-antimatter asymmetry, the origin and decomposition of dark matter, and the nature of electroweak symmetry breaking. These can be addressed through measurements in high-energy scattering experiments. The data collected at the LHC and future colliders will allow stress testing of the SM. Additionally, reinterpreted, these will constrain new physics to energies far beyond the direct production capabilities. The challenge for theory is to match this precision to take maximal advantage of this potential.  Predictions from the SM are derived from perturbation theory in Quantum Field Theory. Including higher orders in the perturbative expansion and all-order resummation systematically improves accuracy. Higher orders in Quantum Chromodynamics (QCD) are especially essential for LHC physics. Accordingly, the European particle physics strategy update recognises precision phenomenology and the corresponding development of techniques and tools as the key to a successful third data-taking period and high-luminosity upgrade of the LHC.  STAPLE aims to combine insights from recent progress in second-order perturbative QCD computations and understanding the logarithmic accuracy of parton-shower simulations to develop a precision event simulation at NNLO+PS accuracy. The event simulation will deliver accurate and precise predictions for scattering processes and will be a STAPLE of precision physics at the LHC and beyond.
Projet ERC : DrugsAndMemory (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : University Hospital Heidelberg — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1498475.0 €

Addiction to drugs is a ubiquitous neuropathological disease that inflicts immense societal costs. A core aspect of addiction that poses a major challenge for treatment is the propensity to relapse in environmental contexts that are associated with drug use. Identification and mechanistic characterization of novel addiction-relevant circuitry linking the motivation to take drugs to the complex spatial and non-spatial features that constitute a drug-associated context are at the core of this proposal. These insights will be used to identify the best constellation of anatomical targets to prevent and reverse the expression of context-triggered drug-seeking. The medial and lateral entorhinal cortex (MEC and LEC) are two central components of the episodic memory system integrating all features relevant for the formation of contextual memory. Crucially, MEC and LEC receive strong bottom-up dopaminergic input from the midbrain and send top-down projections to the nucleus accumbens (NAc). The dopaminergic system is the primary target of all addictive drugs. We will 1) study how bottom-up dopaminergic projections are implemented into drug-context associations in MEC and LEC and 2) determine how these associations influence NAc-mediated drug-seeking behaviour. We will utilize a multidisciplinary approach by developing electrophysiological in vivo recording paradigms in behaving mice that allow the assessment of complex spatial, contextual and non-spatial codes in conditioned place preference and self-administration paradigms typically used to model addiction in rodents. This will be combined with optogenetically-assisted circuit analysis of molecularly-defined pathways to link identified functions to the underlying circuitry. Pathway-specific optogenetic silencing will be used to prevent and reverse the manifestations of drug use on a neuronal and behavioural level. This will guide the evidence-based development of therapies in the future, such as deep-brain stimulation.

Mots-clés : episodic memory,contextual memory,entorhinal cortex,reward,addiction,drugs,ventral tegmental area,motivation,nucleus accumbens,circuitry,optogenetics,behaviour,in vivo electrophysiological recordings
Projet ERC : ImmGenDC (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Helmholtz Zentrum München — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : HMGU
Type d'entité : Recherche
Financement ERC de l'entité : 502322.0 €

Antiviral immunity and autoimmune diseases exhibit high interindividual variability. Despite intensive research, the genetic and molecular basis of this variability is incompletely understood. A key player of the immune system is the plasmacytoid dendritic cell(pDC). Recent single-cell work revealed functionally distinct pDC subsets. Considering that pDCs respond to many pathogens, this highlights a previously underappreciated functional diversity of pDCs. I hypothesize that the genetic regulation of pDCs plays a fundamental role in explaining antiviral response and autoimmune variability. Based on my previous work on immune cells, this genetic regulation is expected to be highly context-specific depending on cell type, cell response, ancestry populations and sex among other factors. The overarching goal of this proposal is to elucidate the context-specificity of immune response and its genetic regulation in pDCs to improve our understanding of human antiviral response variation and pinpoint undiscovered disease pathways of autoimmune diseases. To this end, I will generate population-scale, linked scATAC-, sc3’RNA- and scLong-read cDNA-seq data of baseline and TLR7-stimulated pDCs from healthy individuals across three ancestry populations. I will identify novel pDC subtypes and their immune-regulatory circuits by integrated multiome analyses. Molecular quantitative trait loci(QTLs) and their degree of context-specificity will be used to build prediction models of genetically determined immune responsiveness and decode autoimmune disease loci to develop mechanistically anchored interventions for precision medicine. ImmGenDC will gain fundamental insights into the variability of antiviral immune response that will enable the development of new treatments as exemplified by the current pandemic. Importantly, ImmGenDC will also identify genetic determinants of immune variability across diverse ancestry populations thus paving the way for equitable access to medicine.

Mots-clés : eqtl,human immune system,innate immunity,plasmacytoid dendritic cells,interferon,antiviral immunity,autoimmune diseases,human genetics,immunogenetics,functional genomics,population genetics,gwas,multi omics,precision medicine