Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : TransMit (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Institut Karolinska — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Mutations of mtDNA cause mitochondrial diseases and are heavily implicated in the pathophysiology of age-associated diseases and ageing. Low levels of mtDNA mutations are universally present in somatic tissues of all humans and mtDNA mutations have been reported to contribute to age-associated diseases. Somatic mutations of mtDNA often arise during the massive mtDNA replication in embryogenesis and can accumulate postnatally by clonal expansion. Furthermore, ongoing mtDNA replication during adult life also contributes to the burden of mtDNA mutations in mammalian somatic tissues. Mammalian mtDNA is maternally transmitted without germline recombination and this asexual mode of transmission should theoretically lead to a mutational meltdown over generations, the so-called Muller ratchet. At least two poorly understood mechanisms in the maternal germline counteract the transmission of mutated mtDNA from mother to offspring, i.e., the bottleneck mechanism and purifying selection. The bottleneck mechanism ensures that only a fraction of the pool of mtDNA variation in the mother is transmitted to the offspring. The purifying selection functionally tests mtDNA and decreases transmission of mutations. In this proposal we will use powerful mouse models and completely new experimental strategies to study how mammalian mtDNA mutations are inherited and how somatic mtDNA mutations contribute to age-associated disease and ageing. Maternally inherited pathogenic mtDNA mutations often cause life-threatening incurable diseases with failure of multiple organs in humans. Unfortunately, the principles for inheritance of pathogenic mtDNA mutations are often unclear and the knowledge generated in this proposal will give a better basis for genetic counselling. Furthermore, the mechanisms counteracting a mutational meltdown of the non-recombining, maternally transmitted mtDNA is a central question in biology of great basic scientific interest.

Mots-clés : mitochondria,mtdna,maternal transmission,oxphos
Projet ERC : PRECISION SMOM (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Université de York — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2063192.5 €

Fast and efficient solution-based homogeneous catalysis, or the synthesis of complexes with weakly bound ligands (e.g. methane), often requires the formation of a highly active, coordinatively unsaturated, metal centre. However, the vast excess of solvent can play a detrimental role by competitive coordination, or reaction itself, at the metal centre. Even if solvent does not impede the formation of reactive species, dimerisation can form inactive complexes. These factors quench reactivity and obstruct the formation of reactive complexes that are on the brink of stability, but at the cutting-edge of synthesis and catalysis.  If the problem is the solution, then the solution is to remove the solution!  PRECISION SMOM directly addresses this problem, redefining what is possible in the molecular synthesis of, and catalysis with, highly active organometallic complexes, by offering opportunities in chemical space that extend far beyond what is possible using solution-based methods. It does this by exploiting the Solid-state Molecular OrganoMetallic (SMOM) methods pioneered by Weller; where synthesis, reactivity and catalysis occur in crystallo using precisely-defined molecular single-crystals in solid/gas processes, as shown by the synthesis and reactivity of stable σ-alkane complexes, solving a 40-yr-old challenge in organometallic chemistry.  PRECISION SMOM will use a suite of synergistic studies to understand, and control, the influence of metal site and microenvironment on in crystallo reactivity. Such holistic, fundamental, understanding will promote the translation of SMOM systems into precisely-defined heterogeneous molecular catalysis, focussing on selective and efficient processes for a range of challenging but widely applicable transformations. PRECISION SMOM will change the way we think about reactivity in molecular single-crystals: breaking new ground, embracing wider challenges, and exploiting new opportunities for in crystallo synthesis and catalysis.

Mots-clés : single crystal to single crystal molecular synthesis and catalysis
Projet ERC : DELIGHT (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
Entité participante : Université de Trente — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2117141.0 €

Ultrafast lasers sources open new perspectives in exploring broken symmetry phases as it becomes possible to promote a substantial number of electrons in excited states generating a thermalized electron-hole plasma and leading to reversible or irreversible phase transitions. Light-induced charge density waves, order-disorder transitions, melting, stabilization of topological phases and laser-tunable ferroelectricity have been demonstrated. Experiments are far ahead of theory as few (if any) of the demonstrated light-induced phenomena have been predicted by theory. DELIGHT aims to develop a theoretical strategy to predict and discover photoinduced phases in materials. To accomplish this goal, we will develop quantum-chemical and molecular dynamics schemes including the effect of the thermalized electron-hole plasma on the crystal potential and accounting for light-induced non-perturbative quantum anharmonicity.  DELIGHT will answer these questions: which systems undergo light induced phase transitions ? Can we use light pulses to enhance or tune charge density wave, ferroelectric and magnetic critical temperatures, to generate new topological phases or to optimize the properties of thermoelectric materials ? Can we develop an inverse design strategy, namely given a target property, determine which material will have to be photoexcited and at which fluence to obtain it ?  The proposal will impact chemistry, physics, energy and material engineering. It could lead, for example, to the development of devices with dynamical light switching on/off of magnetism or ferroelectricity, relevant for ultrafast memories, or to the stabilization of new thermoelectric compounds with photo-tunable thermal conductivity and figure of merit. DELIGHT will foster these and similar developments by implementing a fundamentally new and unique database of out-of-equilibrium accessible states of matter that will be a reference for future experiments.

Mots-clés : density functional theory,light matter interaction,ultrafast spectroscopy
Projet ERC : HALFLIFE (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Soci al World and Its Interactions
Entité participante : Université Bar-Ilan — Pays : Israël — Rôle : PI
Acronyme de l'entité : BIU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499967.0 €

HALFLIFE proposes groundbreaking research to understand ageism (i.e., stereotypes, prejudices, and discrimination towards people because of their age) in the second half of life (defined as age 60 and over) to unveil evidence-based interventions to reduce ageism. Unlike other “isms”, we are all bound to experience ageism if we live long enough. The evolving ageing demographics and the detrimental impact of ageism on society at large and older persons alike make the reduction of ageism a public health priority and 1 of 4 pillars of the UN Decade. By moving away from a one-size-fits-all approach, I will develop a theoretically informed, personalised approach to tackling ageism in older persons as agents (targeters) and targets of ageism. The adoption of an intragroup (from within) perspective acknowledges the agency of older persons rather than viewing them solely as victims. This research project will improve the theory and practice of interventions against self- and other-directed ageism among older agents of ageism by identifying the best interventions to reduce self- and other- ageism and recognising the multi-dimensional nature of ageism, including its implicit (unconscious) component. I will advance and integrate theory, research, and practice locally and globally, capitalising on knowledge derived from lay people, research, policy, and practice stakeholders. Relying on an intervention accelerator, I will conduct lab and field randomised controlled tournaments in three countries to develop a portfolio of effective interventions. To ensure the scale-up of the findings, I will develop and support Communities of Practice of practitioners and policy stakeholders at the local and global levels. The project capitalises on my unique position as a core group member of the World Health Organization campaign to combat ageism and as one of 50 UN Healthy Ageing Leaders, as well as on the expertise and dedication of leading researchers and policy stakeholders in the field.

Mots-clés : keywords ageing,older persons,ageism,stigma,discrimination,inequality,intervention
Projet ERC : Cortical Coupling (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Foundation for Research and Technology Hellas — Pays : Grèce — Rôle : Partner
Acronyme de l'entité : FORTH
Type d'entité : Recherche
Financement ERC de l'entité : 196250.0 €

The mechanism for anaesthesia has eluded neuroscience despite being used as a medical intervention for more than two centuries. Two facts are clear: loss-of-consciousness under anaesthesia correlates with a massive reduction in global neuronal signalling and a de-coupling of feedback information. We recently found that the apical dendrites of layer 5 pyramidal neurons are effectively "cut off" from the cell body under anaesthesia and that higher order thalamic input maintains dendro-somatic coupling via the activation of metabotropic glutamate and acetylcholine receptors. We hypothesize that dendro-somatic coupling, the influence of the apical dendrite on the soma, regulates the flow of information around the brain. If true, this would mean that dendro-thalamic coupling is a ubiquitous mechanism by which the brain, via thalamo-cortical interactions, can regulate the degree to which feedback is reintegrated into any given cortical column. Moreover, since human pyramidal neurons are twice as long as rodent neurons, the issue of dendro-somatic coupling in human neurons is even more profound.  Here, we propose to comprehensively investigate this cortical coupling mechanism in vitro and in vivo using state-of-the-art approaches developed in my laboratory and specifically designed to investigate dendritic signalling. We will also perform experiments in resected cortical tissue from human patients using fast-viral expression of optogenetic constructs, an approach that we have also developed and tested in my laboratory. Lastly, we use modelling to probe the consequences of dendro-somatic coupling both for single-cell computation and the principles of multi-compartment neuronal networks.  Dendro-somatic coupling as a dynamic mechanism for global neuronal signalling is a bold new perspective for which we have clear evidence, and which stands to revolutionize our understanding of cortex and possibly also provide insights into more efficient neural network architectures.

Mots-clés : cerebral cortex,dendrites,anesthesia,metabotropic receptors
Projet ERC : QPRESSE (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed Matter Physics
Entité participante : École normale supérieure Paris-Saclay — Pays : France — Rôle : PI
Acronyme de l'entité : ENS Paris-Saclay
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1966268.75 €

Materials under high pressure exhibit exciting topics such as the superconductivity (SC) of hydrogen-rich molecular compounds (super-hydrides) in the long standing search of room-temperature SC. While pressures above 100 GPa can be routinely created in a diamond anvil cell (DAC), the tiny sample volume almost precludes the use of non-optical detection schemes to probe the sample properties. The project idea is to integrate nitrogen-vacancy (NV) centers in the DAC and use the optically detected magnetic resonance (ODMR) of the NV electronic spin to image the Meissner effect. The project relies on our first results where we engineered NV centers on the tip of a diamond anvil and adapted quantum sensing methods to detect pressure-induced magnetic and SC transitions under tens of GPa. By controlling the stress distribution to achieve hydrostatic conditions that preserve the NV symmetry, we have extended this method above 100 GPa, reaching the pressure range of existence of SC in super-hydrides. These materials need to be synthetized at high pressure by laser heating which induces strong inhomogeneities with micron scale. We will use of widefield NV magnetometry to locally image the Meissner effect and the flux trapping in the SC grains whereas the conventional measurements average over the entire DAC geometry and therefore discard all local information. By operating NV sensing on a synchrotron beamline, we will determine the crystal structure of the super-hydrides after the synthesis in the DAC. We will finally couple the spatial detection with noise spectroscopy to measure the temporal current fluctuations in the SC. These methods will be implemented in parallel on Hg-doped cuprates as testbed systems. In a complementary task we will investigate the implementation of NV-based microscale nuclear magnetic resonance in the DAC. Our goal will be to exploit the sensitivity of a dense ensemble of NV centers to detect the chemical shift of the nuclear spins in the sample.

Mots-clés : superconductivity,high pressure,diamond,nv center,quantum sensing
Projet ERC : Q-SCALING (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
Entité participante : Institute of Organic Chemistry and Biochemistry — Pays : Rép. Tchèque — Rôle : PI
Acronyme de l'entité : ÚOCHB AV ČR
Type d'entité : Recherche
Financement ERC de l'entité : 2499115.0 €

Electrical stimuli are essential for a plethora of biological functions. Unlike in electronics, where electrons form currents, nature rather exploits ions as charge carriers. Lack of a consistent molecular picture of action of ions impairs progress in fundamental understanding of ion-controlled biological processes and in designing smart strategies for fixing ion-related pathological conditions. Molecular simulations represent a powerful tool for modelling such processes, however, they can only be as good as is the underlying interaction model (force field). A major drawback of commonly used force fields is the lack of description of electronic polarization, which results in severe artifacts such as a dramatic over-binding of ions, preventing, e.g., accurate modelling of calcium signalling processes. This now well-recognized deficiency hampers faithful modelling of complex ion-involving biological processes. We will employ machine learning techniques to build a de novo comprehensive force field for biological systems, that accounts for electronic polarization in a mean field way via charge scaling. This approach will qualitatively improve modelling of ions in biological contexts without additional computational costs. This will allow us to address accurately the following highly relevant ion-specific processes of increasing complexity from molecular over cellular to organ levels: 1. Dissolution of radical anions of aromatic molecules as key intermediates in technologically and biologically important non-enzymatic and enzymatic Birch reduction processes. 2. Direct membrane translocation of cationic cell penetrating peptides with a potential of drug delivery. 3. Circulation of calcium ions as signalling charge carriers through ion channels of hair cells in the cochlea. At the same time, the newly developed charge scaled force field will be made freely available to the community for further development and ready to be used within major simulation program packages.

Mots-clés : molecular dynamics,force field,electronic polarization,water,salt ions,birch reduction,cell penetrating peptides,ion channels
Projet ERC : Neutros (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Innsbruck Medical University — Pays : Autriche — Rôle : PI
Acronyme de l'entité : MUI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2496900.0 €

Colorectal cancer (CRC) is the second most common cause of cancer death with an alarming rising incidence among young individuals. While the management of early-stage CRC has improved greatly, the median overall survival for patients with metastatic CRC is 30 months. Immune checkpoint inhibitors (ICI) have revolutionized the treatment of advanced solid cancers, yet for CRC continue to lag behind, with the exception of 4% of patients with microsatellite instability. In contrast, several studies have shown limited to no clinical activity of ICI in microsatellite stable (MSS) CRC. A number of clinical trials with drug combinations have been caried out to convert “immune cold” into “immune hot” tumors. However, the objective response rates were disappointingly low. Thus, novel therapeutic concepts are required to improve outcome in MSS CRC patients. We recently built a large-scale single-cell atlas of the CRC tumor microenvironment (TME) and showed remarkable heterogeneity, representing a major challenge in disease management, since patients with the same tumor subtype can have different immunotherapy responses. Moreover, we identified a subset of neutrophils, the most abundant leukocytes in the blood and highly enriched in the CRC TME, that could fuel ICI response. I propose to fill the knowledge gaps on the neutrophil diversity and function in MSS CRC using cutting-edge single-cell techniques and deep learning methods. We aim to: 1) chart multi-omics single-cell neutrophil map of the bone marrow-tumor axis; 2) identify neutrophil cell niches using samples from an ICI clinical trial and spatial single-cell transcriptomics; 3) relate neutrophil cell niches to clinical correlates using a large biobank and spatial single-cell proteomics; and 4) perform mechanistic studies using patient-derived tumor fragments and mouse models. The knowledge gain will lead to rationale for novel therapeutic framework that exploits anti-tumor strategies of the innate and adaptive immunity.

Mots-clés : cancer immunotherapy,artificial intelligence,single cell profiling,cell niches
Projet ERC : LiTeRA (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Texts and Concepts
Entité participante : Sorbonne Université — Pays : France — Rôle : PI
Acronyme de l'entité : Sorbonne U
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2497750.0 €

All modern histories of Western linguistics start with its Greek origins (5th - 3rd cent. BC) and then, after mentioning the Latin Republican polymath Varro (1st cent. BC), jump several centuries to explore only some prominent, late figures (4th - 6th cent. AD). The aim of the LiTeRA project is to provide a holistic perspective on the birth and configuration of Roman linguistic science (2nd cent. BC - 3rd cent. AD), an essential moment in the evolution of Western culture. Although we have inherited valuable sources from the late Latin grammatical tradition, this project will shed light on the overlooked works of the preceding Republican and early imperial periods, a vast body of texts, which have not survived in their entirety, but have been excerpted and quoted in late normative handbooks, commentaries, and lexica. LiTeRA’s three interrelated objectives illuminate how the history of ancient Roman linguistic thought can be substantially rewritten by mobilizing: - A heuristic step: to collect all of the foundational fragmentary texts of Latin grammar, written by a hundred authors and transmitted in the source-texts of late antiquity; - A hermeneutic step: to contextualize the interpretation of the lost texts, extending the sources of Latin grammar to the wider context of ancient Roman scholarship; - A historical step: to reconstruct the evolution of Latin grammatical terminology from its historical roots in the reference corpus of source-texts to its modern conceptualization. LiTeRA’s unique approach to decipher the internal correlations between these related corpora, which are not at all mutually exclusive, will necessitate new methodologies that consider their textual polyphony and intricate technical vocabulary. LiTeRA demonstrates that examining these interconnected issues can only be accomplished in a digital environment that guarantees the interoperability of its objects.

Mots-clés : history of linguistics,ancient grammar,fragmentary texts,linguistic terminology,latin grammarians,ancient scholarship
Projet ERC : REACT (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
Entité participante : European synchrotron radiation facility — Pays : France — Rôle : Partner
Acronyme de l'entité : ESRF
Type d'entité : Recherche
Financement ERC de l'entité : 572500.0 €

Heterogeneous (electro-, photo-) catalysis is at the heart of our modern chemical industry, driving 90% of chemical manufacturing processes. Key challenges include measuring reaction kinetics, identifying intermediates and bridging the “pressure” and “materials” gaps. To study the behaviour of individual nanocatalysts involved in chemical reactions, I will develop new, faster structural and chemical characterisation systems and state-of-the-art in situ monitoring techniques to address catalytic problems. The REACT project will revolutionise our understanding of near-industrial catalysis by overcoming current limitations in pressure and materials science by integrating fast in situ non-invasive three-dimensional imaging of single catalysts with spectroscopy to achieve 3D nanospectroscopic imaging during catalysis. This innovative method will operate at high temperature, pressure and in complex environments, providing atomic resolution and high temporal precision. Taking advantage of 4th generation synchrotron sources, new revolutionary charge-integrating detectors and my recognised expertise in synchrotron coherent X-ray diffraction microscopy, the project will enable 3D study of both the chemistry and structure of nanocatalysts under realistic reaction conditions with unprecedented spatial, temporal and energy resolution, to identify reaction intermediates during catalysis for a deeper understanding of the phenomena critical to nanocatalysis: activity, selectivity, reusability and sustainability. Experiment is nothing without simulation. We will use state-of-the-art atomistic capabilities developed by AI to reveal the full dynamics of catalytic mechanisms, setting a new standard in the integration of computational and experimental sciences. My project will shed light on the most relevant unsolved issues (durability, activity, ...) that limit the efficiency of today's processes and will open new horizons with outstanding impact in catalytic research.

Mots-clés : synchrotron,bragg coherent diffraction imaging,spectroscopy,strain,defects,in situ,operando,co2 reduction,hydrogenation,ammonia oxidation,photocatalysis,