Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : PARTICLES (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
Entité participante : Université Aalto — Pays : Finlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2357623.0 €

Relativistic jets launched by supermassive black holes are the most extreme and energetic persistent phenomena in the Universe. They are capable of accelerating particles to energies inaccessible by particle accelerators on Earth, and deposit enormous amount of energy in their surroundings during their lifetime. They are believed to have a significant impact on galaxy evolution via feedback mechanisms. Yet, despite decades of studies, one of the most fundamental properties, the composition of these jets is still unknown. The jets can consist of either electron-positron pairs, electron-proton plasma where also protons are present and accelerated, or an admixture of the two. The composition affects the power of the jet and the presence or lack of hadrons is a crucial ingredient in modelling the multi-wavelength and multi-messenger emission of these jets. If the jets are hadronic, they are likely the origin of the highest energy cosmic rays.  Circular polarization is the only direct way to determine the particle composition of jets, and we have designed a project that will overcome limitations of previous programs to finally resolve the particle composition of relativistic jets. Previously, this has only been attempted on individual objects at low radio frequencies, or using single-frequency data lacking the required discriminating power. PARTICLES will deliver the first multifrequency-radio high-cadence observations of relativistic jets in total intensity, linear, and circular polarization for a sample of objects. In parallel, we will conduct very long baseline interferometry observations to connect our light curves with the spatially resolved structures in the jets. This unprecedented dataset will be combined with radiative transfer simulations, crucial for modelling the origin of circular polarization. These advances will enable us to answer one of the most central questions related to relativistic jets, what is their particle composition?

Mots-clés : relativistic jets,blazars,radio astronomy,circular polarization
Projet ERC : TRANSPLIC (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : Laboratoire européen de biologie moléculaire — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : EMBL
Type d'entité : Recherche
Financement ERC de l'entité : 1999451.0 €

Trans-splicing is an essential mRNA processing step for a significant portion of living organisms. In trans-splicing, exons from two pre-mRNA precursors merge into a single mRNA, while cis-splicing rearranges exons within the mRNA. Despite recent technical advancements in cryo-electron microscopy (cryo-EM) that movie-like resolved different stages of cis-splicing, the trans-splicing mechanism is still a black box: input and output are defined, but the single steps of how the trans-spliceosome assembles and remodels to initiate the splicing cycle lie in the dark. This limitation is partially due to the absence of molecular structures resolving trans-splicing complexes. In TRANSPLIC, I will pioneer the assembly of trans-splicing complexes on pre-mRNA scaffolds to reveal the particular states unique to trans-spliceosomes. I will determine the molecular structures of trans-spliceosomes and uncover their behavior in the cellular context. Targeted functional assays will disclose the order of events leading to trans-splicing. The protist Trypanosoma brucei (Tb) will serve as an accessible model organism because it uses trans-splicing as an obligatory and abundant mRNA processing step. I will apply an ambitious approach that integrates in vitro and cell lysate-based methods, state-of-the-art cryo-EM, cryo-electron tomography, proteomics, and artificial intelligence-based computational modeling. I will complement the study through targeted functional experiments, leading to a complete understanding of the spatial-temporal resolution of trans-splicing in trypanosomes, with wider relevance to other organisms, including humans. The targeted fusion of gene sequences through trans-splicing bears potential as a molecular tool for transcriptome editing in the future.

Mots-clés : rna processing,trypanosoma brucei,splicing,cryo em,cryo et,biochemistry,protein rna complexes,molecular mechanism,structural biology
Projet ERC : TFCoop (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Laboratoire européen de biologie moléculaire — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : EMBL
Type d'entité : Recherche
Financement ERC de l'entité : 1990221.0 €

Transcription Factors (TFs) are critical regulators of many essential cellular functions such as the acquisition of cell identities in healthy tissues and their dysregulation in disease. Transcriptional activation of a gene typically requires the cooperative binding of multiple TFs, that subsequently recruit various additional cofactors. Genomics has enabled the generation of a near-complete annotation of the cis-regulatory elements and TFs binding them across cell types. Yet, the precise function of each TF in the process and how these functionalities are assembled to activate transcription is an important open question. Here we postulate that despite strong cell-type specificity, the formation of TF cooperativity modules on DNA relies on general principles that are shared across cell-types. In TFCoop we propose to formalise these organizational rules by probing the effect of hundreds of thousands of perturbations of individual TFs on the regulatory activity of their network. We will apply time-resolved nuclear depletion using optogenetics in parallel for multiple TFs of two related networks, and contrast the primary effects of their depletion genome-wide. In a complementary approach, we will develop a reductionist system to study the function of tens of thousands of individual or controlled combinations of TF motifs when inserted into the genome. We will leverage the unique properties of single molecule genomics to measure the contribution of each TF to the activity of multiple components of the regulatory system, across multiple loci simultaneously. This will be followed by factor analysis and deep learning to integrate this large collection of primary effects of TF perturbation and identify the general principles of their assembly into cooperativity networks. Upon success of the project, the resulting models will unlock the understanding of the genetic encoding of cellular identities and allow their manipulation for regenerative medicine.

Mots-clés : transcription factor,cooperativity,single molecule genomics
Projet ERC : STOP-FIX-GO (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : Leiden University Medical Center — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : LUMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999764.0 €

Bulky DNA lesions are a major obstacle during gene transcription by RNA polymerase II enzymes (RNAPII). The stalling of RNAPII at DNA lesions triggers a genome-wide transcriptional arrest. Transcription-coupled repair (TCR) is a specialized DNA repair pathway that selectively removes DNA lesions from actively transcribed genes to restore transcription. Stalled RNAPII at DNA lesions forms a roadblock for advancing DNA replication forks resulting in toxic collisions. The mechanisms that enable the repair of transcription-blocking DNA lesions, the restoration of transcription after repair and the resolution of transcription-replication conflicts are poorly understood. To address these knowledge gaps, I propose to establish a series of innovative approaches aimed at identifying the mechanisms involved in the cellular responses to transcription-blocking DNA damage. We will focus on the functional characterization of known and several promising new TCR factors that we recently identified in combined genome-wide CRISPR and targeted proteomics screens. I propose to dissect the role of known and new TCR proteins by (1) applying a genome-wide approach for directly measuring TCR activity in combination with proximity-labelling proteomics and genetic-interaction mapping to define how TCR complexes assemble and operate, (2) identifying the mechanisms in transcription restoration by combining advanced genomics methods to map nascent transcripts, monitor RNAPII occupancy, and correlate these with specific chromatin modifications in a genome-wide manner, and (3) dissecting the mechanisms involved in resolving transcription-replication conflicts by combining functional DNA replication assays with genome-wide approaches to map transcription, R-loops and DNA replication directionality. This ERC project will break new grounds by offering a detailed understanding of the mechanisms that enable cells to overcome transcriptional roadblocks.

Mots-clés : transcription coupled repair,tfiih,rna polymerase ii,cockayne syndrome,csb,csa,transcription,transcription elongation,dna damage,dna repair,dna replication,r loops,nucleotide excision repair,chromatin
Projet ERC : 3Dwheat (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
Entité participante : Université Paris Cité — Pays : France — Rôle : PI
Acronyme de l'entité : UP Cité
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999995.0 €

In the global warming era, heat stress is a major threat for both yield stability and yield increase. Plants have evolved a variety of sophisticated mechanisms to adapt to challenging environments. Epigenetic regulations allow them to dynamically reprogram their transcription machinery to adapt to an ever-changing environment. Both histone marks and the 3D organization of the chromatin are instrumental for this coordinated regulation of gene expression according to environmental cues. Yet, the overwhelming majority of available data on chromatin dynamics in response to stress has been obtained in Arabidopsis, and cannot be directly transferred to crops. Due to the expansion of NGS technologies, we are currently facing a change of paradigm, empowering the development of genome-wide approaches on crops. In this project we focus on wheat. Wheat is the 1st cereal worldwide for trade, and the demand is expected to increase by 60% by 2050. My main objective is a thorough understanding of the priming for heat stress resistance in wheat. To this end, I propose to develop a new tri-dimensional (D) functional genomics approach, integrating epigenomic (1D), transcriptomic (2D) and chromatin architecture (3D) data to elucidate the molecular basis for priming in wheat. Moreover, this project will go beyond addressing the challenge of deciphering epigenetic regulatory processes underlying priming. It also includes the development of innovative tools for novel breeding strategies that will harness epigenetic variability in addition to genetic diversity. We propose to generate a new generation of molecular markers that do not rely on DNA sequence polymorphisms, and that can be readily used in traditional breeding programs as such, or as complementary tools for efficient QTL introgression. Such markers will be used to tag new traits, to follow a new generation of alleles as well as to unveil new types of genetic diversity in existing collections of germplasms.
Projet ERC : SFEER (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
Entité participante : Université de Valence — Pays : Espagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1979422.5 €

We present SFEER (Star Formation Efficiency in the Epoch of Reionization), an ambitious project to enable one of the most significant and long-lasting leaps in our understanding of early galaxy formation. The discovery of exceptionally massive galaxies in the distant Universe has confronted us with puzzling questions about how galaxies could assemble so efficiently at early cosmic times. Unfortunately, significant instrumental limitations have prevented us from robustly reconstructing their physical properties. The recent launch of the James Webb Space Telescope (JWST) has ignited a revolution. Its exquisite sensitivity and spatial resolution are going to provide dramatically new information on massive galaxies in the the Epoch of Reionization (EoR) and beyond. SFEER is set to play a dominant role in this process. At its core is a cycle 1 JWST/NIRSpec program I am leading which will obtain spatially resolved spectroscopy for 12 exceptionally bright galaxies in the EoR. Remarkably, estimates of the interstellar medium (ISM) reservoirs of this sample are already in our hands thanks to recent Atacama Large Millimeter Array (ALMA) observations, providing information on their molecular gas and dust content, and the fraction of obscured star formation. This joint dataset clearly stands out in the panorama of current JWST programs, and constitutes an important benchmark. SFEER will enable to probe the assembly history of these tantalizing objects through the characterization of their ages, stellar mass, energy-balanced star-formation rates, metallicity, merging fractions and gas kinematics, and their relationship with the host dark matter halos. Taking advantage of complementary JWST programs and wide-area multi-wavelength data from ground and Euclid, we will extend our results to higher and lower masses, and probe galaxy formation from the earliest points in cosmic time.

Mots-clés : high redshift galaxies,epoch of reionization,lyman break galaxies,galaxy stellar populations
Projet ERC : MARIS (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Soci al World and Its Interactions
Entité participante : Vrije Universiteit Brussel — Pays : Belgique — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1968787.5 €

Two of the most profound sources of exclusion in current-day societies are people’s ethnic and social origins. The main goal of MARIS is to examine the interlinked patterns of different dimensions of racism and intergenerational social immobility at the level of societies. Racism refers to the historically grown beliefs and practices that systematically disadvantage some ethno-racial groups. It has been conceptualized and measured by different research traditions, which each focuses on another aspect of racism. Intergenerational social immobility refers to the transmission of parents’ socioeconomic positions to those of their children. Also here, there are different traditions to examine these positions. What both racism and social mobility research have in common, is that there is little interdisciplinary integration of their dimensions. This is a serious gap, because each approach only covers a specific aspect and often yields different answers to basic research questions. Therefore, MARIS starts with a theoretical and empirical integration of four dimensions of racism at the macro-level: discriminatory behaviour, perceived discrimination, explicit attitudes and implicit bias. The macro-approach will consolidate the recent macro-social turn in racism research and opens a new paradigm of research questions. In the same vein, I also integrate four dimensions of social mobility: social class, status, income and education. In the next step, MARIS examines the interlinked patterns of racism and social mobility at the macro-level. While racism and immobility are intertwined in people’s lives and I can theoretically expect four possible combinations of both sources of exclusion, previous studies tend to examine them separately. By combining both, this project bridges two long-standing research fields within the social and economic sciences. Lastly, I analyse varying levels in racism and mobility across countries and time by their links with macro-policies and recessions.

Mots-clés : discrimination implicit bias prejudices intergenerational social mobility social class income education
Projet ERC : FLUX (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth System Science
Entité participante : Vrije Universiteit Brussel — Pays : Belgique — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2631000.0 €

For the last 4.5 billion years, extraterrestrial (ET) materials have continuously bombarded the Earth. Today, the Solar System debris that reaches the Earth’s surface is dominated by particles less than 2 mm in size, termed micrometeorites (MMs). Until recently, the established misconception was that these MMs did not survive geological timescales, limiting reconstructions of the dust flux through time that are currently based on finding rare relict mineral phases or applying geochemical tools (e.g., Ir contents, 3He isotope ratios). Following a successful proof-of-concept study on a Late Devonian section, FLUX proposes first to extract fossil MMs from selected stratigraphic intervals across the Phanerozoic to document their characteristics and origin and second to use them as a novel high-resolution proxy to better understand the dynamical interactions between the Solar System and Earth. As such, fossil MMs may serve as an alternative new source of information on Solar System processes, complementary to classic meteorites. By combining expertise in meteoritics, geochemistry, and chemostratigraphy, FLUX addresses the following questions: 1) How did the flux of cosmic dust evolve during the Phanerozoic? 2) Can stratigraphic intervals marked by a dramatic increase in the mass of cosmic dust accreting to the Earth be identified? 3) Do increased ET flux events reflect asteroid family-forming events in the asteroid belt between Mars and Jupiter, and are they influenced by changes in the shape of Earth’s orbit? 4) Can oxidized iron-rich MMs be used to reconstruct the gross primary productivity or atmospheric CO2 levels of the deep past? 5) Did ET flux fluctuations affect the global Earth environment, for example through ocean fertilization? Ultimately, FLUX will better position the Earth in the context of a dynamic Solar System and constrain the causes and consequences of the variations in the flux of cosmic dust to Earth.

Mots-clés : micrometeorites stratigraphy asteroid family forming events atmospheric co2 levels ocean fertilization
Projet ERC : SINATRA (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Vrije Universiteit Brussel — Pays : Belgique — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1726250.0 €

The intensifying great power competition between the United States and China has arguably become the structuring vector in international politics. This project examines to what extent the European Union (EU) is able to autonomously make decisions regarding its relations with the United States and China. The key innovation is to present a comprehensive theory to explain to what extent and under what circumstances external or internal actors have the upper hand in informing European policy choices in Sino-American competition. Assuming the existence of a correlation between the EU’s (degree of) unity and autonomy, the latter is depicted as a relative and contingent concept.  The main hypothesis is that the EU’s degree of autonomy vis-à-vis China and the United States will be high in those policy areas where it enjoys exclusive competences, moderate where it has shared competences, and low where the competences rest with the member states. I expect this to happen despite the high degree of “issue linkage” (Haas, 1980; McGinnis, 1986) between the different areas of EU external policy; despite the fact that the United States and China will try to exploit Europe’s dependence in some areas to extract concessions in others; and despite the fact that the EU itself will try to build on its competences in some areas (e.g. trade) to expand its clout in others (e.g. foreign and security policy). SINATRA pushes back against the conventional wisdom that the EU is either poised to become an autonomous subject or condemned to the status of mere object or battleground in Sino-American competition, by arguing that the EU will be subject and object at the same time, and unpacking the mechanics of that tension.  The project draws on mixed methods research, combining quantitative analysis of European, American and Chinese voting patterns and public discourse (i.e. through the use of content analysis software and manual coding) in a variety of international organisations and debates

Mots-clés : european strategic autonomy great power competition transatlantic relations
Projet ERC : U-Tube (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Université Érasme de Rotterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : EUR
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Chronic kidney disease (CKD) affects one in ten people worldwide and is often progressive. Progressive CKD not only causes kidney failure, but also premature aging, cardiovascular disease, and loss of quality of life. Currently, progressive CKD can only be diagnosed after irreversible damage to the kidney has already occurred. There is therefore an urgent need for earlier biomarkers. The kidney consists of filters and tubules, but diagnosis of progressive CKD is currently based on filter function alone. This is surprising, as it is tubular injury that drives CKD progression, and it is the tubule that is targeted by recently developed kidney-protective treatments. U-Tube therefore aims to identify and apply next-generation biomarkers for kidney tubular function to facilitate the early detection and treatment of progressive CKD. My central hypothesis is that the factors that cause tubular injury and CKD progression, are present in urine and therefore detectable as biomarkers. I will focus on urinary microcrystals and extracellular vesicles (EVs) as the drivers of tubular injury, which I will first study in tubuloids using a multi-omics approach. Subsequently, I will perform a large-scale analysis of crystallization and EVs in urine samples from people with stable or progressive CKD. I will then single out those biomarkers that can be targeted by kidney-protective treatment. These targetable biomarkers will be moved forward for the development of a high-throughput tubular panel that I will test for its potential to predict progressive CKD, compared to a gold standard test for tubular function. U-Tube will use cutting-edge innovations to identify urinary biomarkers for tubular function that are targetable and implementable in clinical practice. If successful, it will advance the prediction of CKD progression, and as such redefine how we assess kidney health. By enabling early kidney-protective treatment, U-Tube has the potential to vastly improve CKD outcomes.

Mots-clés : chronic kidney disease extracellular vesicles proteomics tubular function urinary biomarkers