Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MIMIC (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
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 €

Scientific Challenge: Immunotherapy has revolutionized cancer treatment, yet only a minor fraction of patients respond to frequently used immunotherapeutic treatments. T cell recognition of peptide-major histocompatibility (pMHC) class I complexes is essential to maintain immune surveillance and eliminate cancerous cells. Numerous products of genetic and epigenetic alterations can serve as targets for T cell recognition of cancer, yet our capacity to predict what MHC-embedded targets T cells can recognize on the surface of cancer cells is still poor, with a less than 5% hit rate. While we have robust tools for prediction of antigen presentation, we still have very limited understanding of the factors driving immunogenicity – i.e. which of the presented targets will give rise to a T cell recognition. A fundamental mechanism influencing T cell recognition is molecular mimicry. It has long been proposed that the ability of a given T-cell receptor (TCR) to recognize multiple different pMHC complexes is essential to provide immunological coverage of all potential pathogens that we may encounter. T cell epitopes, that at first glance appear very different, may have structural similarities once embedded in the MHC I binding groove, and hence appear similar to the given TCR (molecular mimicry).  Objective: In MIMIC, I will determine the role of molecular mimicry in T cell recognition and demonstrate how pre-existing immunity may shape the T cell recognition of cancer antigens. I will use the SARS-CoV2 infection as a model system to understand molecular mimicry, and apply the learnings from this to cancer immunogenicity. Expected outcome: I predict that by understanding the influence of molecular mimicry, the rules governing the immunogenicity of T cell epitopes can be determined and the selection of antigens optimized - this will be essential to develop precision T cell therapies targeting tumor antigens of relevance for the individual patient.

Mots-clés : t cell cross recognition,t cell receptor,computational prediction tools
Projet ERC : DOPAGE (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : Université de Turku — Pays : Finlande — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1200000.0 €

Many older adults experience impairment of cognitive functions, such as memory. While changes to the aging brain are often assumed to underlie cognitive decline, but it has turned out surprisingly hard to identify coupled brain-cognitive changes in aging. This challenge is magnified when searching for potentially modifiable brain alterations that could serve as targets for various kinds of interventions. A promising candidate mechanism is age-related alterations in neurotransmitters like dopamine (DA) and noradrenaline (NA), crucial for brain functions. Yet, existing models of aging related to DA and NA are inadequate, as past studies solely focused on either the DA or NA system and also emphasized a single facet of the multifaceted DA system (either pre- or post-synaptic). This represents a serious omission because various parts of the DA system are tightly regulated and the balance between pre- and post-synaptic markers, rather than each marker in isolation, might be more critical for efficient neuromodulatory function. Contrary to the prevailing notion of a global DA neurodegeneration, characterized by a hypodopaminergic condition, I hypothesis that aging is accompanied with loss of balance between pre- and post-synaptic DA systems. This imbalance holds profound implication for functional brain integrity and cognitive decline in aging. The overarching goal of this ground-breaking research program is to, for the first time, address the fundamental question of how the dynamic interplay between pre- and post-synaptic markers of the DA, along with its interaction with equally critical NA, evolves as individuals age and how these dynamics are linked to functional brain integrity and cognitive decline. Of particular interest is whether transiently restoring the balance between pre- and post-synaptic components of the DA system and NA through pharmacological intervention, opens a window to remodel the aging brain and improve cognitive function in some older individuals.

Mots-clés : pet,mri,dopamine,aging,cognition
Projet ERC : CoM-BraiN (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Université technique du Danemark — Pays : Danemark — Rôle : Partner
Acronyme de l'entité : DTU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 500994.0 €

Axonal bundles in cerebral white matter form the structural basis of functional brain networks, enabling effective integration of neural activity. The axonal connections are not homogenous structures. Axons differ in diameter and myelination, enabling signal conduction at different velocities. This axonal diversity is a clinically relevant microstructural feature, as neurodegenerative or neuroinflammatory processes can affect axon diameters differently. Recent advances in Magnetic Resonance Imaging (MRI) have enabled the non-invasive mapping of the microstructural properties of brain network connections in live brains. But attempts to correlate these structural features with brain function have not yet been successful. I have pioneered the mapping of axon diameters that are directly linked to the conductive properties of axonal connections by using diffusion MRI in living human brain. Also, I have established an unique cross-disciplinary validation setup for such methods by combining nanoscopic 3D Synchrotron Radiation Imaging and functional cell-specific targeting techniques. By Conduction Velocity Mapping in Brain Networks (CoM-BraiN) I will be able to unravel the altered functional dynamics of the microstructural connections in the diseased brain. Methodologically, I will push the frontiers of MRI by creating a new translational CoM-BraiN framework for non-invasive and in-vivo studies in animals and humans. Clinically, CoM-BraiN will provide a new window into the characterization of neuropathological changes in the diseased brain and contribute to the identification of structure-function fingerprints of psychiatric and neurodegenerative disorders that are thought to be a major pathogenic factor in many brain diseases.

Mots-clés : brain network,mri,degenerative disease,animal,human,axon,myelin,validation
Projet ERC : REBOUNDLESS (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Human Mobility, Environment, and Space
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 : 1999478.0 €

Society´s most well-intended efforts to solve sustainability challenges have not yet achieved the expected gains due to rebound effects, which are unintended consequences of interventions that arise due to induced changes in system behaviour. Rebound effects are widely acknowledged, but fundamental scientific gaps hamper their prevention. REBOUNDLESS aims to develop the reboundless design theory, a paradigm shift in design science that will establish the scientific knowledge for preventing rebound effects by:  - Explaining systemic rebound effect mechanisms triggered by sustainable design strategies. - Modelling and simulating the magnitude of rebound effects arising from design decisions. - Enabling the design of resilient systems by means of reboundless design strategies.  The reboundless design theory will provide novel methodologies, simulation models and strategies for the design of reboundless solutions (i.e. products, product/service-systems and socio-technical systems that are resilient to rebound effects).  Building on the strong foundation of systems theory, REBOUNDLESS is uniquely positioned to bridge the interdisciplinary gap in the interplay of sustainable design and rebound effects, qualitative and quantitative models, engineering and social sciences, theory and practice. The reboundless design theory will be the starting point of a prominent research field, with extensive applicability within and beyond sustainable design (e.g. sustainability assessment, sustainability transitions, policy-making).  Never before has there been a stronger global focus on solving the pressing sustainability challenges, but the expected positive societal impact will not be achieved unless rebound effects are prevented. Building on my 15-year track-record on sustainable design theory and practice, REBOUNDLESS will give me the opportunity to enable the urgently needed shift towards the design of sustainable and resilient systems.

Mots-clés : rebound effects,sustainable design,system dynamics,design science,ecodesign
Projet ERC : ADVHANDTURE (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer Science and Informatics
Entité participante : Institut national des sciences appliquées de Rennes — Pays : France — Rôle : PI
Acronyme de l'entité : INSA de Rennes
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999750.0 €

These last years have seen an explosion of novel tactile technologies providing various haptic sensations across all the user's body. However, while these technologies have now been made available, virtual reality systems are still struggling to convey compelling tactile sensations for 3D interaction. As of today, tactile feedback mainly fails: (1) to render multiple haptic stimuli in a spatially coherent manner, (2) to achieve temporal integration of the stimuli compatible with the interactive framerates of immersive environments and (3) to preserve user's immersion within virtual worlds. ADVHANDTURE aims at targeting all the above limitations by introducing a ground-breaking computational approach for handling multimodal tactile feedback within immersive environments. My original methodology proposes for the first time the introduction of perceptual data at each step of the design of the computational models dedicated to immersive tactile haptics. Thanks to its innovative approach, ADVHANDTURE will address the design of: (a) physics-based models able to simulate the rendering of various tactile inputs, (b) computationally-efficient algorithms integrating multimodal tactile stimuli within immersive environments and (c) 3D interaction paradigms for combining multimodal tactile stimuli with multi-sensory information.  In addition to significant advances in the design of computational haptic rendering models, ADVHANDTURE, in the long run, will considerably enrich our 3D interaction with virtual worlds by providing realistic multi-sensory feedback with multiple tactile sensations. Thanks to its multidisciplinary aspect, ADVHANDTURE will propose synergistic outcomes contributing to our understanding of the haptic perception of virtual worlds, as well as the underlying models in the fields of Computer Graphics, Haptics and Virtual Reality.

Mots-clés : haptics,virtual reality,physics based modeling and simulation,computational framework,perceptual measurements,3d interaction
Projet ERC : SynSig (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : Université de Haïfa — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2122524.0 €

Human beings constantly go in and out interpersonal interactions in their daily lives; these interactions are assumed to have critical effects on mental health. But how such interactions affect mental health is poorly understood. SynSig suggests that interpersonal synchrony is an individual-specific mechanism underlying curative relationships. It seeks to go beyond the one-size-fits-all “the higher the synchrony the better” theoretical assumption underlying the state of the art research. It is the first to propose that individuals have their own individual-specific trait-like synchrony signature as manifests across interacting partners. It further proposes that to make interactions curative, it is necessary to induce an individual-tailored correction to such a signature. That is, the amount and direction of the changes in synchrony must be guided by the individual’s synchrony signature. To develop an individual-specific understanding of synchrony, SynSig focuses on curative interactions encapsulated in time and space: the therapeutic relationship between the client and therapist. It will investigate the existence of individual-specific synchrony signature and how individual-tailored correction of the signature serves as the mechanism transforming relationships into curative ones. It will implement multimodal markers (motion, acoustic, physiological, facial expression) for disentangling the trait-like synchrony signature and state-like deviations from it, of individuals participating in multiple dyadic interactions with humans and virtual humans. The first multimodal feedback system on momentary deviations from the signature will be developed and used to facilitate individual-tailored changes in synchrony and draw causal inferences between such changes and mental health outcomes. The findings will provide new insights into the multi-layered individual-specific nature of synchrony, and bring us closer to understanding how human connections affect our mental health.

Mots-clés : psychotherapy research,patient therapist relationship,therapeutic alliance,working alliance,mechanisms of change,psychotherapy process,personalized treatment,interpersonal synchrony,randomized controlled trial,major depressive disorder,motion synchrony,acoustic synchrony,physiological synchrony,processes of therapeutic change,psychotherapy feedback system
Projet ERC : CancerMultiOm (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
Entité participante : Université hébraïque de Jérusalem — Pays : Israël — Rôle : PI
Acronyme de l'entité : HUJI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

To comprehend the characteristics, phylogenetic relationships, and drug resistance of tumor subclones, measurements must be performed at single-cell or single-clone resolution. Aims 1 and 2 aim to create cost-effective and reliable single-cell drop technologies for capturing full-length RNA (Scfl-RNA-Seq) and enhancers at the DNA level (ChromOpen). It is noteworthy that Scfl-RNA-Seq also captures non-coding and non-polyadenylated RNAs besides coding mRNA. ChromOpen also offers better capturing of functional enhancers and higher sensitivity compared to the conventional technology. The ultimate goal of Aim 3 is to create the first technology that can capture both full-length RNA and enhancers from the same cell (Multi-Omics). To increase sensitivity and coverage, Multi-Omics will be combined with a 3D-culturing system (3Dclone) that facilitates growth of primary cancer cells into small clones. The single-clone based Multi-Omics maps will increase the discovery rate of genetic somatic diversity, including non-coding regions, reveal connections between gene expression and mutated loci, and display a wider range of functional state associations between cells. In Aim 4, using our innovative mapping technologies, we will investigate two brain tumors: Non-Small Cell Lung Cancer that has spread to the brain and Glioblastoma primary cells. Both of these cancers have limited treatment options and poor outcomes due to drug resistance. Based on temporal drug treatment experiments and advanced mapping technologies, this data will improve our understanding of somatic driver mutations and cellular diversity in the context of resistance, and ultimately, lead to the identification of new therapeutic targets.

Mots-clés : single cell technologies,high throughput sequencing,epigenomics,clonal dynamics,3d culturing system,drug resistance,brain tumors
Projet ERC : QFTinAdS (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental Constituents of Matter
Entité participante : École polytechnique — Pays : France — Rôle : PI
Acronyme de l'entité : X
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1930051.0 €

The importance of quantum field theory (QFT) in modern theoretical physics is hard to overstate. Nevertheless a proper mathematical framework to describe field theories is still lacking. This is felt most concretely in the world of scattering amplitudes, whose general properties are difficult to define from existing axioms. This hampers our ability to make progress in understanding strongly coupled field theories. In contrast, for conformal field theories (CFTs) there has been remarkable progress in recent years. The key ingredient here is the operator product expansion, which both significantly constrains correlation functions and whose associativity conditions can be analyzed numerically. These techniques are however only suitable for theories with a conformal symmetry, which normally only emerges at the endpoints of finely tuned RG flows.  To advance the non-perturbative understanding of strongly coupled non-conformal QFTs new methods are needed. Among other things it is imperative to grasp the non-perturbative structure of scattering amplitudes. I propose to follow two interlinked paths based on recent results. The first approach concerns the flat-space limit of a QFT in a fixed hyperbolic background known as Anti de-Sitter (AdS) space. The second approach can be called the numerical S-matrix bootstrap. Both approaches hold great promise, but by pursuing them jointly I will be able to optimally leverage insights from one approach into the other.

Mots-clés : quantum field theory
Projet ERC : DIACHRONY (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Studies of Cultures and Arts
Entité participante : Université hébraïque de Jérusalem — Pays : Israël — Rôle : PI
Acronyme de l'entité : HUJI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

This proposal argues for a quantum shift in the way we theorize about music. In the past three decades, music theory has been dominated by synchronic theories based upon typologies. The value of these theories notwithstanding, there are three significant “blindspots” that arise from a purely synchronic perspective. First, synchronic approaches are incapable of explaining trends – they at best capture “snapshots” along a timeline, but cannot explain processes: how one snapshot progressed to another. Second, music written between two snapshots is evaluated in synchronic approaches either according to a defunct model, or according to one that had not yet come into existence, as often occurs with the music of the generation between Bach and Mozart. Third, such snapshots mask trends during their period of interest behind a false façade of stability. I propose to address this problem through a diachronic methodology, designed to focus not on definitions and synchronic typologies, but rather on processes of change over time. To this end I will carry out a corpus study of unprecedented scope, covering 1700 works between 1680-1819. In two overlapping subprojects based upon the same corpus, I will examine trends in four fields: large-scale form; phrase structure; cadences (musical units signifying closure); and schemata (stock musical phrases). Tracing the diachronic process of change across the decades of the corpus, I will reveal the forces that propelled music from one style to another, and through this, the tensions with which composers were faced and to which they responded. Furthermore, my novel diachronic approach will enable a more flexible mode of accounting for the fuzzy limits of theoretical definitions and histories. Lastly, with its original conceptual premises and its corpus-based methodology, this project will serve as a model for a new approach to music theory, encouraging the embrace of a diachronic perspective in other fields of music theory too.

Mots-clés : eighteenth century music corpus studies music theory cadences schema theory sonata form formenlehre
Projet ERC : DETOXPEST (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
Entité participante : Université suédoise des sciences agricoles — Pays : Suède — Rôle : PI
Acronyme de l'entité : SLU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999720.0 €

Insects numbers and diversity have rapidly declined in the EU and worldwide. Pesticides, and particularly the toxicity of insecticides to non-target insects (e.g. bees), are one of the major drivers of insect declines. Apart from destabilizing natural ecosystems, pollinator disappearance directly threatens food security. To help combat insect decline, I propose an innovative approach for the damage-activation of pro-pesticides (DAPP) by plant proteases that are activated in the gut of feeding caterpillars. Non-target beneficial insects that cause no damage, including pollinators and natural enemies of pests, are spared. My team pioneers the study of proteolysis in the plant wound response, following our recent discovery that physical damage activates a class of proteases, called metacaspases. I hypothesize that i) damage-activated plant proteolysis is a largely unrecognized but potential key player in the plant wound response to insect herbivores and ii) this knowledge can be used to enhance pesticide biosafety. We will study the impact of fall armyworm (Spodoptera frugiperda), an invasive insect pest and potential major threat to EU agriculture, on the model plant Arabidopsis thaliana and the economically important crop maize. A combination of advanced (N-terminomics) and novel (Proteome Integral Solubility Alteration) proteomics technologies will allow us to uncover unknown plant metacaspase substrates and damage-activated proteases and to assess their impact on insect herbivory. These fundamental studies will feed information into a pipeline of first-in-class DAPP development, where we will modify biological insecticides with newly-discovered protease cleavage sites. Finally, we will test toxicity against target (Spodoptera) and non-target insects. My early-stage and fundamental research on damage-activated proteolysis can have a tremendous positive impact on the increase of insecticide selectivity to help combat the escalating problem of insect decline.

Mots-clés : insect decline,plant wound response,arabidopsis,maize,protease,proteomics,n terminomics,genome editing,insecticide