Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MULTI2D (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Materials Engineering
Entité participante : Université de Linköping — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999940.0 €

Emerging materials science and nanoscale engineering spawn extraordinary structures. During my ERC-StG, I discovered a new family of internally-ordered 3D atomic laminates that I coined i-MAX. More recently, these phases have been used to derive a new type of 2D solids, MXenes, with ordered vacancies. Here, I consolidate research to establish a world-leading research environment with a mission to understand and exploit yet wider classes of unique functional materials; the next generation of 2D materials, beyond MXenes, from selective etching of recurring layers in 3D precursor solids. Fundamental investigations of this project have as objectives to: 1) Use a theory-assisted search, including screening of open data bases, for design of new multifunctional 2D materials. 2) Perform precise-controlled synthesis/derivation of novel 3D/2D materials based on chemical exfoliation. 3-4) Explore nanoscale engineering and property tailoring, specifically targeting 2D materials for energy storage, catalysis, and other areas where low-dimensional solids can provide unique and sustainable solutions. 5) Provide proof-of-concept for novel materials in device applications. Research breakthroughs and corresponding societal impact are envisioned as novel 2D materials provide superior properties in devices made from sustainable elements and processing. Functionalized freestanding sheets of new 2D materials are expected to have a major impact on supercapacitors and batteries, and as a catalytic material, realizing efficient hydrogen evolution. Initial results attest to this. Pioneering a new generation of 2D materials holds exceptional potential for discoveries, for use in applications meeting global challenges pertaining to energy and environment, and beyond. My experience as an international research leader gives me confidence to take on this greater challenge for innovation. Thus, an outstanding research constellation can be constituted, delivering groundbreaking research.

Mots-clés : laminated materials,chemical exfoliation,two dimensional 2d materials,selective etching,density functional theory dft,high throughput simulations,sustainability,fundamentals,applications
Projet ERC : PredictCOPD (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Biomedical Research Networking Center on Neurodegenerative Diseases — Pays : Espagne — Rôle : Partner
Acronyme de l'entité : CIBERNED
Type d'entité : Recherche
Financement ERC de l'entité : 30001.5 €

Chronic Obstructive Pulmonary Disease (COPD) has been traditionally understood as a self-inflicted disease caused by tobacco smoking occurring in old individuals. Over the past few years, however, our group and others have proposed that the pathogenesis of COPD goes beyond smoking, and that there is a range of lung function trajectories through life (trajectome); some of them have roots in early life and can lead to COPD, cardiovascular and metabolic morbidity as well as premature death, while others are associated with healthy ageing. Here I propose that, detrimental gene (G) and environment (E) interactions occurring early in life (T) constitute a ‘first injury hit’ that alters the normal lung developmental program and modify the pace of normal lung aging by reducing the resilience of the lungs to future GxExT interactions. Accordingly, lifelong GxExT interactions determine the individual trajectome and, eventually, the occurrence of COPD and associated multimorbidity. PredictCOPD aims to identify the interactions and mechanisms that determine which individuals will develop COPD and multimorbidty at some point of their life. The specific aims are: 1) to identify the lifelong environmental and host risk factors associated with the trajectome, COPD and multimorbidity, 2) to use a novel liquid biopsy method to identify biological factors driving the trajectome, COPD and multimorbidity; 3) to identify clinically relevant preventive and/or early therapeutic targets integrating the results from aims 1 and 2 with novel analytical approaches and 4) to validate findings both in vitro and in other available cohorts. The project will leverage from several available population and COPD patient studies with available clinical data and biological samples. The results of PredictCOPD have the potential to: 1) promote healthy ageing by preventing and eventually eradicate COPD and associated multimorbidity; and, 2) change COPD treatment from palliative to causal.

Mots-clés : lung trajectories,copd,multiborbidity,aging
Projet ERC : ModLogic (Horizon Europe, appel 2022, 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 : 1999565.0 €

Chromatin modifications are a key mechanism for regulating gene expression patterns in normal and disease settings. Nonetheless, despite the ubiquity of epigenomics data, the causal functions of specific chromatin modifications have proved challenging to unravel. This knowledge gap reflects limited approaches to dissect how chromatin modifications influence transcription quantitatively and context-dependently, across diverse genomic features or variants in any given cell-type. Here, we propose to systematically interrogate the functional impact of specific- and combinatorial- chromatin modifications within tens-of-thousands of contexts in living cells, using a novel modular epigenome editing platform. We will produce the largest precision chromatin-perturbation dataset to date, and exploit it to capture multi-modal functional responses at allelically-resolved single-cell resolution, across developmental lineages. The unprecedented scale of the work will uncover the regulatory logic by which distinct chromatin states interact with genomic motifs, sequence variants, and cellular identity, to shape quantitative gene expression patterns. By integrating data and deploying genetic screens, we will further identify the trans-acting and cis-structural mechanisms that underpin complex relationships. Our technology will circumvent the key limitations of existing approaches, by excluding pleiotropy and redundancy, whilst systematically isolating functional genome x epigenome interactions. The cumulative insights will be used to build a predictive model based on rational rules for how specific changes in chromatin marks instruct - or reflect - gene expression states within specific contexts. This will aid design strategies for precision medicine, and create guiding principles to attribute functional significance to epigenome profiles in health and disease.
Projet ERC : RNP5D (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 : 2614460.0 €

This proposal brings together the fields of bacterial transcription, translation and DNA repair with state-of-the art single-molecule biophysics in vitro and in vivo, biochemistry and structural biology to address a central but understudied question in biology: how are different macromolecular processes interconnected and functionally coupled? I aim to elucidate this by investigating the crosstalk between central processes in bacterial gene expression: transcription, translation and DNA repair. First, to understand what determines whether transcription is coupled to translation, we will reconstitute the complete transcription-translation system in vitro and image the process in real-time using cutting-edge multi-color single-molecule fluorescence experiments. We will support our dynamic single-molecule data with structural information from cryo-electron tomography. In order to verify that our in vitro data also have physiological relevance, we will electroporate reconstituted and labelled RNAP/ribosome complexes into live E. coli cells for multi-color single-molecule imaging also in vivo. Second, we will reconstitute the transcription-coupled DNA nucleoside excision repair pathway in vitro. Integrating multi-color single-molecule fluorescence with optical tweezer assays, will allow us to resolve a controversial point on how transcription-coupled DNA repair starts, comparing the established concept of Mfd-initiation with the newly proposed UvrD/RNAP-mediated lesion recognition. Finally, we will develop single-molecule experiments for integrating all three processes, specifically transcription, translation and DNA repair, into a single system to quantify cooperativity and competition between individual components and processes. Overall, this proposal will provide quantitative and mechanistic understanding of how central processes to gene expression are functionally interconnected, setting a new benchmark for examining complex biological systems in context.

Mots-clés : transcription,translation,dna repair,ribosome,rna polymerase,interconnections between macromolecular processes,single molecule fluorescence microscopy,ribonucleoprotein assembly,protein rna interactions,rna folding,rna dynamics,co transcriptional processes,fret
Projet ERC : COntrol (Horizon Europe, appel 2024, 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 : 2558835.0 €

The formation of crossovers during meiotic cell divisions is a crucial process to produce sperm and egg cells. This mechanism not only secures proper chromosome segregation but also enhances genetic diversity, playing an essential role in sexual reproduction and evolutionary adaptation. Disruptions in the regulation of crossover events can have detrimental effects on individual organisms and entire species populations. Thus, crossover formation is tightly regulated by both positive and negative pathways. Crossover assurance guarantees that each pair of homologs undergoes at least one crossover, facilitating proper segregation. Simultaneously, crossover interference prevents individual crossovers from occurring too closely within the genome, minimizing the risk of damage. However, the molecular mechanisms of these key regulatory processes and the functional coupling between them are still not understood. To dissect the regulatory mechanisms of crossover formation, we have achieved a groundbreaking visualization of this process in vivo, employing advanced imaging technology and AI-powered image analysis. Our approach includes real-time imaging and correlative super-resolution microscopy for temporal and structural analysis of key steps in crossover formation. In COntrol, I will now exploit these tools to acquire the quantitative data necessary to obtain a mechanistic understanding of crossover regulation. I will develop and rigorously test biophysical models through precisely targeted genetic perturbations, harnessing C. elegans' unique toolset of advanced real-time imaging and genetics. Furthermore, I will validate the uncovered mechanistic principles by examining their conservation in the vertebrate model system zebrafish. COntrol will thus shed light on one of the most fundamental questions in biology, namely how organisms distribute and shuffle genetic information among their progeny while maintaining the genetic integrity of future generations.

Mots-clés : meiosis,crossover formation,imaging,image analysis,super resolution microscopy
Projet ERC : TRACE (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Soci al World and Its Interactions
Entité participante : Université de Coimbra — Pays : Portugal — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1999930.0 €

Sexual and gender diversity are constitutive elements of democratic societies which have been targeted by extreme-right populism and other anti-democratic forces. Taking queer citizenship as a set of criteria through which democracies can be evaluated, TRACE explores the extent to which the EU has influenced local political and socio-legal advancements in LGBTI+ rights, narratives and experiences over time. To respond to this aim, TRACE develops an innovative age-sensitive, analytical lens focused on ageing, ageism and age-related LGBTI+ politics through which progress and backlash in countries that experienced substantial changes in their intimate citizenship regimes will be investigated. TRACE uses a multiscale life-course approach centred on gendered/sexed processes of ageing in the context of a rapidly changing Europe. LGBTI+ elders carry a unique embodied knowledge of struggle and resistance, offering a precious lens through time, from once criminalized outlaws to the intimate citizens of today’s EU LGBTI-freedom zone, who outlasted a variety of challenges, including the AIDS pandemic and related stigma. The countries included in this research are Portugal, Italy, Greece, Malta and Slovenia, offering a comprehensive overview of changes across time and space in Europe, including the impacts of religion and secularism, traditional and advanced intimate regimes, and the relation to the EU LGBTI+ evolving framework. With a focus on the South as an imagined political space of silence and resistance, the research enables an in-depth portrait of different regions of Southern Europe today, grounded on the life stories of older adults whose lifespan accompanies these changes. Their shared and untold past of oppression will inform scholarly knowledge regarding current and future policymaking, particularly timely in a rapidly changing Europe grappling with the expansion of populism and anti-gender backlash.

Mots-clés : life course biographic narrative interpretive method bnim lgbtqi ageing democracy embodied memory european union populism and anti gender backlash
Projet ERC : HYDROCHIRAL (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
Entité participante : Université de Valladolid — Pays : Espagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Chirality and water both play key roles in various aspects of biological functions and disentangling water’s role in chiral recognition in biological processes is paramount to ultimately understanding the origins of homochirality. HydroChiral proposes to do this by developing ground-breaking instrumentation that uses broadband molecular rotational spectroscopy combined with supersonic expansions, buffer gas cell technology, and novel chiral capabilities to explore pressings topics at the forefront of water research and chirality such as the generation and characterization of chiral water, the generation of larger water clusters to examine the first solvation shell, and absolute configuration determination for analytical applications. This technique will differentiate between enantiomers, diasteriomers, and conformers within complex gas mixtures while enabling the study, at an unprecedented accuracy, of the chiral water structures that form in the solvation of biomolecules and unravel the active role of water in most biological processes. The project will demonstrate the use of chiral techniques that have been developed for rotational spectroscopy on molecular clusters for the first time, and it will use enantiomer-selective population transfer techniques to tilt the racemic nature of chiral water clusters and create enantiomerically enriched water. The proposed research encompasses my three fields of expertise to perform cutting-edge research in water cluster science, chirality and solvation using the advantageous features of rotational spectroscopy. The outcomes of HydroChiral will open new horizons for not only fundamental research in physical chemistry and molecular physics but also in applied fields ranging from analytical chemistry to asymmetric synthesis in pharmaceutical applications such as drug discovery, where absolute configuration determination is crucial.

Mots-clés : chirality chiral water chiral imprinting water clusters solvation shell water research hydrogen bond rotational spectroscopy instrument and technique development
Projet ERC : ADProbe (Horizon Europe, appel 2022, 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 : 1999625.0 €

Post-translational modification of proteins is essential in regulating proper cellular homeostasis. The attachment and removal of the small protein Ubiquitin (Ub) is amongst others involved in regulating immune response, cell cycle progression and proteasome mediated protein degradation. The (de)conjugation of adenosine-di-phosphate ribose (ADPr) on the other hand is essential in regulating DNA damage responses and apoptosis. ADPribosylation and ubiquitination both dictate a highly complex signaling code and intriguingly these two PTM systems also communicate, as Ub was recently found to be ADPribosylated on multiple different positions. This new layer of controlling ubiquitination plays important roles in intracellular bacterial replication, DNA damage repair and tumor development. Understanding this fascinating post-translational interplay and the role the different UbADPr-isotypes play in cell biology is crucial to develop novel strategies for therapeutic intervention in diseases such as infection diseases and cancers. What are the mechanisms, biochemical scope of protein-protein interactions, cell biological consequences and differences between these non-studied UbADPr linkages? I propose to study the entire system of dynamic ADPribosylation of Ub and explain the molecular details of the (de)conjugating enzymes, explore the cell biological networks involved and exploit the key enzymes for inhibitor discovery en-route to future therapeutic intervention. I will develop novel chemical methodologies and create a set of new substrates, activity-based probes and assay reagents and use them to profile specificity and preferences of the involved enzymes, study the interactions and pathways in cells and screen for small molecule inhibitors. Using my expertise in protein synthesis and chemical- and structural biology I aim to unveil the details of this until now poorly studied, but crucial, hidden layer of post-translational interplay in an unbiased manner.

Mots-clés : ubiquitin,adpribosylation,protein synthesis,activity based probes,inhibitor discovery,proteomics,chemical synthesis,post translational modifications,profiling enzyme activity,structural details
Projet ERC : GUnDHam (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : École internationale supérieure d'études avancées — Pays : Italie — Rôle : PI
Acronyme de l'entité : SISSA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1444033.0 €

This project aims to prove rigorous results on the generation of unstable dynamics in the dispersive Hamiltonian water waves and geophysical fluid equations: I refer to the outstanding open problems of the formation of energy cascades from low to high frequencies, orbital instabilities and extreme rare phenomena such as rogue waves. All these behaviors are well documented in experiments, real world data and numerical simulations, but still lack a rigorous mathematical proof. Accordingly the project has three lines of research:  1) Energy cascades from low to high frequency modes: I plan to construct solutions of water waves and geophysical fluids equations in which energy shifts from low to high Fourier frequencies, induced by resonant interactions, provoking the growth of Sobolev norms. This will be attacked via a novel mechanism based on dispersive estimates in the frequency space, that I have pioneered in the linear setting;  2) Orbital instabilities of Stokes and Rossby waves: I plan to study the linear and nonlinear modulational instabilities of traveling solutions like the Stokes and Rossby waves in the higher dimensional setting, proving long-time conjectures in fluid dynamics and geophysics. This will be attacked by extending a program I have initiated in the one dimensional setting;  3) Extreme phenomena formation: I plan to construct rogue wave solutions of the water wave equations, confirming (or disproving) two of the most renowned physical conjectures regarding their formation. This will be achieved combining deterministic normal forms and probabilistic methods, like large deviation principles applied to PDEs.  These goals aim to open new paradigms to understand the long time dynamics of dispersive Hamiltonian partial differential equations originating from fluids.

Mots-clés : dispersive hamiltonian fluids,energy cascades,modulational instability,rogue waves
Projet ERC : FuncAmyloid (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : DESY — Pays : Allemagne — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2000000.0 €

Self-assembly of proteins and peptides into amyloid fibrils produced across kingdoms of life is associated with antimicrobial activity, microbial pathogenicity, and a wide range of diseases. The correlation of fibrillation and morphology to function is poorly understood, and high-resolution structural information and mechanistic models are lacking. Our lab pioneered the atomic-level analysis of bacterial amyloids and eukaryotic functional fibrils involved in cytotoxicity, biofilm structuring, and antibacterial activity. We revealed novel morphologies extending beyond canonical amyloid cross-β structures of tightly mated β-sheets, to include, for example, cross-α fibrils composed on amphipathic α-helices. In addition, we exposed a unique lipid-induced cross-α/β secondary structure switch in fibrils of the same sequence. Here we investigate amyloid fibrils which serve as key virulence determinants in S. aureus and Pseudomonas acting as cytotoxins and in biofilm scaffolding, and as antimicrobials produced across different species. We will leverage the knowledge and expertise, and newly emerging methods in electron, light and force microscopy, to understand how fibrillation propensity, fibril morphology and structural switches are connected to function, membrane interactions and toxicity mechanisms at high resolution. The findings are expected to identify structural features that underlie the formation, regulation, and activity of these fibrils, providing advantages in specific environments. Understanding these structure-function relationships will help to clarify the link between amyloid formation and antimicrobial activity. We will use the insights gained from these studies for the rational design of antimicrobial peptides and small molecules targeting virulent determinants towards potential applications in the management of infectious diseases. Our findings on functional amyloids can overall advance life, material, medical and environmental sciences.

Mots-clés : amyloids,fibrils,self assembly,antimicrobial,virulence,structure,cryo em,cryo clem