Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : LIVINGPORE (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Université de Valence — Pays : Espagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1998974.0 €

The conformational flexibility and biological function of proteins is dictated by the positioning of a few amino acids into specific arrangements linked by peptide bonds. We intend to implement this same principle of sequencing, essential to biology, to synthetic porous materials by encoding pore environments with atomic precision to control structural response and function. The road to this vision remains blocked by the lack of methodologies and understanding which is required to untap the value of pore chemistry in controlling the conformational response of frameworks and encapsulated guests. LIVINGPORE is structured around the complementary concepts of ‘transformable’ and ‘transformative’ porosity, that share the use of amino acid side chain chemistry and peptide bond rotations for selecting the conformational response and function of flexible frameworks (oligopeptide linkers) or flexible guests (small enzymes) by using programmed pore settings and mutants. We will develop both concepts in parallel by implementing a central high-throughput workflow that integrates computational and experimental routines for rational design and accelerated discovery. These synergic, multidisciplinary tools will be used to i) guide chemical synthesis, ii) evaluate structural response and iii) rationalize function, all required for going beyond what can be currently achieved with conventional methods. The central objective of this materials chemistry project is to lay definitive understanding on how reticular frameworks can be used to respond to (transformable) or select (transformative) specific molecular recognition patterns for cooperative selection in a crystalline solid. The long-term vision is a shift in the present perception of Metal-Organic Frameworks into unique porous materials capable of structural/functional responses closer to biological systems that enable distinctive applications currently unthinkable of, here initially demonstrated in separation and biocatalysis.

Mots-clés : metal organic frameworks reticular chemistry porous materials functional inorganic materials structural flexibility pore chemistry high throughput methods chiral separation enzyme immobilization synthetic chaperones molecular recognition conformational selection protein inorganic hybrid interface
Projet ERC : HEART_STATES (Horizon Europe, appel 2021, Consolidator 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 : 2000000.0 €

Organs consist of cells with a large diversity of specialized roles. A fundamental question is how these cells mount a coordinated response in space and time to maintain or restore organ function after perturbation. Recent progress in single-cell genomics has generated the opportunity to understand this process on a system-wide scale. We will use the adult zebrafish heart as a powerful model system to dissect how regeneration after injury is orchestrated by the activation response of multiple different cell types. To understand how activated cell states are generated and how they interact to drive the regenerative process, we will:  1) Define which cell types react to injury and measure their activation profiles. We will develop new experimental and computational strategies for measuring cell states, including a “molecular time machine” that records the past transcriptome of single cells based on RNA labeling.  2) Discover the mechanisms that induce cell state activation upon injury. We will combine single-cell transcriptomics and open chromatin profiling to infer gene regulatory networks, and we will use functional experiments to validate the identified pathways.  3) Reveal pro-regenerative cell types and understand their role in the regenerative process. We will combine spatial transcriptomics and computational analysis to identify putative cellular interactions, and we will use targeted cell type depletion and signaling inhibition to confirm our findings.  In this manner, we will provide the first comprehensive view of how cell type activation leads to a synergistic response in organ regeneration. Furthermore, the approaches and concepts developed in this project will be applicable to other systems in regeneration and beyond. Finally, understanding the underlying mechanisms in zebrafish, the preeminent model for heart regeneration, will open up exciting avenues for awakening the dormant regenerative potential of the human heart.

Mots-clés : cell state transitions,single cell genomics,rna labeling,lineage tracing,spatial transcriptomics,heart regeneration,zebrafish
Projet ERC : WhatsMRI (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Université de médecine de Graz — Pays : Autriche — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Magnetic Resonance Imaging (MRI) is widely established, with 50,000 scanners worldwide and more than 100 million diagnostic scans conducted yearly. Myelin acts as the electrical insulation of neuronal fibers and is essential for motor, sensory, and cognitive functions and is composed of several lipids and proteins arranged in a specific geometry. However, myelin loss occurs regionally in inflammatory diseases like multiple sclerosis, myelitis, and optic neuritis, and it also serves as a biomarker of aging.  Despite the availability of various MRI-based approaches for detecting myelin, there remains a significant gap in systematically validated knowledge regarding how myelin's lipids, proteins, and structural variations influence MRI signal generation. Furthermore, there is no gold standard for assessing the constituents of myelin, and conclusions are primarily based on MRI of formalin-fixed tissue.  Quantitative post-mortem MRI of unfixed human brains in situ, combined with subsequent mass spectrometry imaging (LA-ICP-TOF-MS, MALDI-MSI), small-angle X-ray scattering (SAXS), and microscopy (CARS, TEM, IHC), will enable histologically enriched modelling of tissue and the simulation of fundamental MRI parameters (relaxometry, susceptibility, and diffusion) to reveal causal relationships with chemical elements, matrix composition, structure, and common molecules of myelin, neural fiber orientation, and biometals. In addition to 20 control brains, 10 brains from deceased individuals with multiple sclerosis will be recruited to broaden the spectrum of myelination under investigation.  This research addresses the fundamental biophysical mechanisms underlying MRI of myelin and chemical elements, which currently lack validation. We will establish a publicly available elemental and histochemical atlas of the human brain and identify how histological features causally contribute to quantitative MRI parameters.

Mots-clés : mri,relaxometry,susceptibility,validation,iron,myelin,chemical elements
Projet ERC : ACT (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Soci al World and Its Interactions
Entité participante : Université de Copenhague — Pays : Danemark — Rôle : Partner
Acronyme de l'entité : KU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 512586.25 €

The Big Two of agency (influence, resourcefulness, authority) and communion (benevolence, prosociality, honesty) are fundamental to human social cognition, the self-concept, and personality. The Big Two must have a tremendously important function for humans, otherwise they were not that fundamental to human psychology. Yet, what is this function? State-of-the-art answers explain the function of the Big Two either in social cognition or in the self-concept or in personality and those answers contradict each other in critical ways. Here, I propose the first all-encompassing answer to the functional question of the Big Two in social cognition and the self-concept and personality. My answer comes in the form of a novel theory: Agency-Communion Theory (ACT) of Social Learning and Cultural Activity. According to ACT, the Big Two are the chief enablers of high-fidelity social learning. Never before have the Big Two been considered relevant for high-fidelity social learning, but the latter is widely seen as the reason for humans’ capacity to build culture and thrive by cultural activity—humans’ most powerful evolutionary strategy. Thus, ACT considers the Big Two the essential building blocks of human cultural activity and, ultimately, of humans’ extraordinary evolutionary success. ACT’s novel portrayal of the Big Two entails a wide variety of previously unforeseen behavioural consequences, including a novel account of social influence. The state-of-the-art account presupposes the existence of an innate tendency to conform to majority norms. ACT questions the existence of such an innate tendency and offers an alternative with far-reaching implications for many theories across social sciences and urgent societal challenges in the sphere of social influence. My interdisciplinary team will empirically test ACT and its novel account of social influence. We will use new, tailor-made methodology in laboratory experiments, formal evolutionary models, Big Data, and panel studies.

Mots-clés : big two of agency and communion,fundamental content dimensions in psychology,evolutionary personality psychology,social learning strategies
Projet ERC : NEWROCK (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth System Science
Entité participante : Université de Copenhague — Pays : Danemark — Rôle : PI
Acronyme de l'entité : KU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1970878.0 €

The plethora of Earth-like exoplanets indicate that planet-formation is efficient, highlighting the need for unravelling the pathways to forming habitable worlds. The new planet-formation paradigm, i.e. pebble accretion, suggests that mm-to-cm sized pebbles are the main planetary building blocks as opposed to colliding proto-planetary bodies. Bulk samples of meteorites from asteroids, leftovers from the early Solar System, have been long used to infer the nature of Earth’s precursor material. However, pebble accretion predicts that pebble-like components of primitive chondrite meteorites provide a more accurate record of the precursor material to terrestrial planets, including the source of volatiles critical to life. The most abundant chondrite constituents are mm-sized chondrules hypothesized to be the pebbles driving planet formation. Chondrules formed within 5 Myr of the Solar System thus represent time-sequenced samples that can probe the nature of the matter, including its environment(s), that accreted to rocky planets. We will elucidate the origin and history of the matter precursor to terrestrial planets, by studying chondrules, matrix and refractory components in chondrites. This information is key for understanding the initial conditions allowing the formation of Earth-like planets. Combining isotope fingerprinting, age-dating and petrology, our data will be obtained using state-of-the-art techniques, including next generation collision cell and thermal ionization mass spectrometry as well as high-resolution imaging. We will identify the precursor matter to terrestrial planets and probe how its composition varied in space and time, identify the disk environment where the primordial population of planetesimals seeds formed and evaluate the role of thermal processing and outward recycling in modifying inner disk matter. With these goals, including high-risk high-gain ventures, we are in a strong position to make step change discoveries in cosmochemistry.

Mots-clés : meteorites,chondrules,isotopes,nucleosynthetic anomalies,chronometry
Projet ERC : MechanoFate (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cell Biology, Development, Stem Cells and R egeneration
Entité participante : Université de Copenhague — Pays : Danemark — Rôle : PI
Acronyme de l'entité : KU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

During embryonic development, an unspecialized cell mass is transformed into complex tissues and organs through collective movements and cell interactions. The acquisition of such structural and functional diversity is powered by two main processes: morphogenesis, which sculpts cells into tissues and organs, and cell fate acquisition, which assigns specific identities to cells. Despite extensive research, the intricate coordination between these two processes remains elusive. Mechanical forces determine the shape and structure of tissues, and their impact on cell fate has been recently uncovered, emphasizing the significance of mechanics in regulating both morphogenesis and cell fate. However, understanding the relationship between these two processes is complex, as it requires the integration of cell shape, cell behavior, mechanics, and gene expression across the tissue over time. In this project, we will apply cutting-edge biophysical and data science methods to the mucociliary epithelium of Xenopus embryos to dissect the role of mechanics in both morphogenesis and cell fate acquisition in vivo. We will first determine how cells undergoing fate acquisition trigger local tissue rearrangements that lead to global morphogenetic movements. Next, we will investigate the impact of tissue mechanics on cell fate and transitions. Finally, we will combine cell behaviors, gene expression, and mechanics into a model to predict cell fate. By exploring the ways cells respond to and modify their mechanical surroundings and the circumstances in which external forces determine cell fate, we will uncover the basic principles of complex tissue formation. This research will give us a comprehensive understanding of how individual cells, as mechanical elements, interact to form a tissue structure that is more than just the sum of its parts. The findings will have a significant impact on other tissues, particularly the human airways, and advance our knowledge of embryonic development.

Mots-clés : biophysics,tissue mechanics,mechanics of cell fate,multiomics,scrnaseq,mechanical forces,xenopus,mucociliary epithelium,epithelial mechanics,embryonic development,mechanical probing,machine learning,quantitative imaging,live imaging,cellular behavior,tissue stretching,tissue rheology
Projet ERC : TOPO2_REPAIR (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : Université de Copenhague — Pays : Danemark — Rôle : PI
Acronyme de l'entité : KU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Topoisomerase II (TOP2) chemotherapeutics such as etoposide have been widely used in the clinic to treat leukemias, lymphomas, lung, testicular, and ovarian cancers. Etoposide was first approved for clinical usage in 1983. By intercalating into DNA, etoposide stalls the TOP2 catalytic cycle, generating toxic DNA lesions known as TOP2-DNA-protein crosslinks (TOP2-DPCs). After 40 years of intense research, the mechanisms employed by cells that counteract these lesions are starting to emerge. These include enzymes that reverse the crosslink, degrade the protein adduct, or remove the lesion by DNA incisions. Moreover, the protein ZATT was recently described as an essential regulatory enzyme that SUMOylates TOP2 and thereby stimulates TOP2-DPC resolution. Important and long-standing questions in the field relate to our understanding of how the different modes of repair are activated, coordinated between one another, and preferentially used by cells. Based on genetic data, ZATT appears to be the primary responder to TOP2-DPCs but how ZATT coordinates the different modes of repair via TOP2-SUMOylation is currently unclear. To address these questions and study TOP2-DPC repair, we propose to use a novel approach based on Xenopus egg extracts, which can recapitulate DNA repair mechanisms in a soluble environment. As part of our preliminary data, we show that these extracts can recapitulate TOP2-DPC repair via ZATT SUMOylation, providing a unique opportunity to delineate the molecular mechanisms underlying this reaction. By combining this system with complementary and innovative approaches, we seek to obtain a clear molecular understanding of the different mechanisms counteracting TOP2 lesions and unravel the molecular triggers that activate the different routes of repair. By doing this, we will provide new opportunities and targets to improve cancer treatment.

Mots-clés : dna repair,dna replication,topoisomerase,dna protein crosslinks
Projet ERC : STONE (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Study of the Human Past
Entité participante : Slovenian Academy of Sciences and Arts — Pays : Slovénie — Rôle : PI
Acronyme de l'entité : SASA
Type d'entité : Recherche
Financement ERC de l'entité : 2583380.0 €

Stećci are medieval tombstones dispersed throughout Bosnia and Herzegovina, Croatia, Montenegro and Serbia. Still preserved in situ in tens of thousands in the landscapes, they are common grave markers of the Late Medieval and early Ottoman (12th C - 16th C) Western Balkans’ plural societies. Although erected in the geographical region known for the ‘medley of peoples,’ stećci are not attributed to any ethnic or religious group and have always been considered enigmatic, lacking a clear, explicit belonging. The sheer number and dispersed distribution have hampered stećci scholarship, confining our understanding of this heritage to visual information and historical overviews. This multi-scale, multi-proxy archaeological project will integrate innovative and multidisciplinary approaches to study medieval funerary archaeology. The principal goal is to understand the social life of the society that left us these remarkable monuments. Focusing on medieval Herzegovina, the cradle of the stećci phenomenon, the proposed research into the social lifeways of these monuments will redefine the scholarship of the medieval Western Balkans funerary culture and situate it within a European context, significantly raising its visibility within international scholarship and the public domain. In addition to increasing our understanding of stećci, STONE will establish a discipline of medieval epigraphy in the Western Balkans; introduce epiconography, a conceptually innovative approach to study inscriptions and decorations on stećci; use a prehistoric landscape approach to investigate medieval landscape and initiate a paradigmatic shift away from the current culture-historical approach to the study of past societies. The proposed research will serve as a propulsive force within Western Balkan medieval archaeology, enabling it to make a decades-long leap to align with current medieval European funerary and research trends.

Mots-clés : medieval archaeology,funerary archaeology,social archaeology,social memory,archaeological science,digital humanities
Projet ERC : REASSESS (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth System Science
Entité participante : Institut national de recherche pour l'agriculture, l'alimentation et l'environnement — Pays : France — Rôle : Partner
Acronyme de l'entité : Inrae
Type d'entité : Recherche
Financement ERC de l'entité : 0.0 €

Over just three decades, the Greenland Ice Sheet contribution to sea-level rise has grown six-fold. Increased basal slipperiness from increased surface melt was initially proposed as a key mechanism reinforcing ice loss, but a wealth of studies deconstructed this idea, leading the Intergovernmental Panel on Climate Change (IPCC) to conclude that increased surface melt “has not led to sustained increases in glacier flux”. Last year, however, my group re-established meltwater as a primary mechanism driving ice dynamics, albeit in a different manner than previously envisioned. Basal slipperiness is not set by melt rates but by ice-sheet morphology, which drives low slipperiness in steep and fast glaciers that terminate into the ocean, and high slipperiness in gentle and slow glaciers that terminate on land. As a result, a previously unforeseen meltwater-ice dynamics feedback potentially drives a higher than anticipated mass loss as glaciers transition from marine- to land-terminating in the future. In this project, I plan to REASSESS the control of surface meltwater on ice loss from the changed paradigm that glacier morphology rather than melt rates controls its impact. (AIM1) will probe the mechanisms responsible for the morphology control on basal slipperiness by overcoming long-lasting observational challenges through an innovative seismologically- and geodetically-based monitoring scheme exporting recently established proofs of concept for the first time to Greenland. (AIM2) will predict the control of meltwater on ice-sheet evolution from incorporating the new observational insights from AIM1 into a hierarchy of small-scale physical to large-scale parametrized models. With this strategy, we will, for the first time, fully evaluate the dynamical response of the Greenland Ice Sheet to surface meltwater and its impact on sea-level variations under deglaciation as inferred in the past and expected over the coming centuries.

Mots-clés : ice sheet dynamics,subglacial hydrology,basal friction,seismology,geodesy,geophysics,instrumentation,modelling,climate change,sea level