Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MetaQ (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : Université de Pavie — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2107750.0 €

Enzymes have been classically investigated as standalone catalysts operating in a relatively diluted milieu. However, the cell micro-compartments are highly crowded environments and biological catalysis cannot be fully understood on the bases of simple diffusive models. We are tackling this challenge by reconstituting a full-scale biosynthetic pathway where multiple enzymes coordinate within a metabolon - a structurally defined setting that allows the vectorial transfer of substrates and products. Our system for exploration is the fascinating biosynthesis of coenzyme Q, an essential redox mediator for many pathways. The juxtaposition between its highly polar head group and hydrophobic tail renders this compound a challenging feat to handle. To synthesise its highly substituted aromatic head group, nature has amassed a large soluble supra-molecular complex consisting of no less than eight functionally distinct proteins that adheres to the inner-mitochondrial membrane. This infrastructure can extract the substrate whilst providing a shielded, hydrophobic environment for molecular transit. We will systematically characterize the functional, structural and evolutionary aspects of the involved protein machineries in interplay with the membrane. Our approach starts by exploiting ancestral sequence reconstruction to generate proteins of enhanced stability. We will build the metabolon in vitro to assess how the enzymatic activities are coupled in the context of a metabolon. Structural studies will reveal how the active sites are spatially organized with respect to the order of the enzymatic steps and substrate trafficking. Our integrated strategy will unveil the pivotal evolutionary transitions that create a biosynthetic machinery. This research will go beyond classical enzymology by exploring a new paradigm of cellular biochemistry where metabolic pathways are fuelled and governed through interactions between enzymes, and between enzymes and other proteins.

Mots-clés : metabolon,biological catalysis,multienzyme complex,enzymology,enzyme mechanism
Projet ERC : JUST PEN (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Nantes Université — Pays : France — Rôle : Partner
Acronyme de l'entité : NU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 56250.0 €

The JUST_PEN Project aims to analyse the strategies private interest groups use to try to influence European penal and prison policies through notably litigation and judicial complaints lodged with the European Court of Human Courts and the Court of Justice of the European Union. In relying notably on a current national research grant on “the European Human Rights Justice under Moral Influences?”, the JUST_PEN project will analyse whether or not the moral and religious values promoted by these private interest groups have influenced and have even been taken account of or even been adopted by the European penal and prison policies. In this respect, the project will investigate the ways in which these private interest groups try to influence these policies using doctrinal, judicial (notably through litigation and monitoring efforts) and political tactics. In terms of effects of these strategies, we will investigate how and to what extent these tactics are translated into penal and prison policies notably through a process of coercive human rights that refer to the coercive aspect (the enactement of criminal law and the use of criminal sanctions) of human rights protection. In doing so, we will propose a new theoretical model: the ‘moral entrepreneur of jurisprudence ’ that is all about powerful private actors who do not behave as philantropists but are driven by material interests taking creative initiatives which involve shaping or reshaping case law on penal and prison policies. In doing so, they can either reinforce or on the contrary moderate and even lenify the coercive dimension of human rights and contribute though this process to orient significantly penal and prison policies. The JUST_PEN project intends thus to achieve a significant paradigm shift within the existing literature on human rights, European law and penal and prison policies by combining all these domains that are ignored by the existing legal, socio-legal and criminological literature.

Mots-clés : penal and prison policies,ngos,conservative and liberal interest groups,european human rights justice
Projet ERC : METH-POL (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Université de Leeds — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499924.0 €

The ambition of the Global Methane Politics project is to produce a pioneering body of research that simultaneously establishes the distinctiveness of methane politics, investigates and demonstrates the most significant political obstacles to methane emissions reduction, and has transformative impacts on global methane and climate policies and practices.  Research on methane politics is urgently needed because 1) methane is the second largest contributor to anthropogenic climate change; 2) reducing methane emissions provides one of the most obvious routes to short-term climate mitigation, including limiting warming to near 1.5°C; 3) methane has become widely recognised as an important international policy concern since the launch of the Global Methane Pledge (GMP) in 2021; and yet 4), very little research has so far been conducted on methane policy, regulation or politics in practice - which is a critical shortcoming if the GMP target of a 30% reduction in emissions by 2030 is to be more seriously pursued. METH-POL will be novel, impactful and timely. Guided principally by research in political ecology, it will test a series of original hypotheses about the specificity of methane politics, the political barriers to methane emissions reduction, and the implications thereof for research, policy and practice. It will produce the first dedicated body of cross-sectoral, cross-national, multi-scalar, trans-disciplinary and comparatively informed evidence on methane politics. It will involve research on 16 countries, on the global North and global South, on every continent, on the top five methane emitting countries, on the major methane emissions sectors, and on a wide range of methane governance initiatives, institutions and techniques. And it will also involve extensive knowledge exchange with scientific, policy and practitioner communities. A 5-year project, METH-POL will run from 2026 to 2030 – the critical years if the GMP 30-30 target is to be achieved.

Mots-clés : methane,political ecology
Projet ERC : LSYM (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental Constituents of Matter
Entité participante : Société Max-Planck pour le développement des sciences — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : Société Max Planck
Type d'entité : Recherche
Financement ERC de l'entité : 2458045.94 €

In modern physics we are faced with the unsatisfactory situation that the Standard Model (SM), which condenses our current state of knowledge in the form of quantum field theories, despite its spectacular success in the prediction of laboratory results, fails in explaining even the most basic properties of our Universe, such as the disparity of matter and antimatter and the possible existence of dark matter. In the quest to search for answers to these questions, low energy, high precision experiments in ion traps have taken a pivotal role by allowing precise tests of the charge, parity and time (CPT) reversal symmetry. I propose an ambitious, next-generation Penning-trap experiment that will enable us to directly compare the magnetic moments of electron and positron at 14 digits precision. To this end, we will simultaneously trap a single positron and an electron in the same trap and directly compare their spin precession frequencies. To enable the co-trapping of the oppositely charged particle and antiparticle, we will bind the electron in a hydrogenlike 4He+ ion. As a result of the binding, the spins of both particles show a slow beat, which can be accurately measured. Any deviation of this beat frequency from the prediction by quantum electrodynamics (QED) reveals a CPT violation. This way, LSYM will enable a uniquely sensitive comparison of particle and antiparticle charge, mass and g-factors and thus yield the most stringent CPT test in the lepton sector. To this end, we will develop a novel, superconducting Penning trap apparatus, which can be cooled to millikelvin temperatures to largely eliminate black-body radiation. Building upon techniques recently pioneered by my group, LSYM will allow the coherent “quantum” measurement of the difference of the spin precession frequencies. Furthermore, with this toolbox at hand, we will have access to a new class of intriguing measurements, such as an order of magnitude improved determination of the electron atomic mass.

Mots-clés : penning trap,precision physics,g factor,electrons,cpt,antimatter,qed
Projet ERC : GenRevo (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Société Max-Planck pour le développement des sciences — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : Société Max Planck
Type d'entité : Recherche
Financement ERC de l'entité : 1966117.57 €

The regulation of genes is generally accepted to play a key role in shaping phenotypes. However, how regulatory sequence encodes complex morphological structures remains unsolved. This is due to our lack of understanding of how enhancers, promoters, and other regulatory components work together to control and fine-tune gene expression. As such, one of the major challenges of the post-genomic era is to uncover the sequence code that controls gene expression and, ultimately, the phenotype. In GenRevo, I propose to study the genomics of an extreme example of evolutionary adaption, the wings of bats, as a model system to identify and functionally dissect how sequence determines phenotype. Our approach involves the genetic re-engineering of bat regulatory sequence in mice and their functional dissection to identify the essential components that govern gene expression and phenotype. Based on an already generated comprehensive data set from mouse and bat limb buds, we will detect, re-engineer and dissect intra- and interspecies differences in regulatory landscapes linked to batwing development. In particular, we will 1) determine what non-coding features are essential for maintenance and/or change in gene expression, 2) reconstitute bat-specific regulatory landscapes in mice by genome engineering synthetically produced large DNA sequences, 3) dissect how genomic changes translate into altered gene expression and phenotypes on cellular and regulatory level, and 4) create de novo designer regulatory landscapes that can be used as a testbed for experimental perturbations. Collectively, GenRevo will produce ground-breaking knowledge in our understanding of how gene regulatory units work in vivo and how variants influence phenotypes. The possibility to re-engineer sequences in another species will spark a technological revolution in the functional analysis of mammalian genomes, particularly regarding the function of non-coding DNA in human diseases, traits, and evolution.

Mots-clés : gene regulation,genome editing,limb development,regulatory landscapes
Projet ERC : ER-REMODEL (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Cell Biology, Development, Stem Cells and R egeneration
Entité participante : Université Johann Wolfgang Goethe de Francfort-sur-le-Main — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2496691.0 €

The endoplasmic reticulum (ER) is the most extensive endomembrane system of the cell that undergoes continuous remodelling and adaptation to fulfil required functions in synthesis and transport of cellular components. A major driver of ER remodelling is ER-phagy, a selective autophagy pathway that targets excess or damaged portions of ER for degradation. By linking the ER membrane to the autophagic machinery, ER-phagy receptors play central roles in this process. However, beyond the identities of ER-phage receptors, we have little understanding of the mechanisms underlying ER-phagy and the dynamics of ER remodelling. This proposal aims to decipher the mechanisms by which ER-phagy receptors, especially those containing reticulon-homology domains (RHD), drive the dynamic process of ER remodelling in a cell-type specific fashion. We will determine how ER-phagy is regulated by site-specific receptor ubiquitination and by the formation of ER-phagy receptor clusters, particularly how ubiquitination regulates cluster size, dynamics, localization, identity and composition. We will combine structural, computational and functional approaches to determine, at the highest possible resolution, how ubiquitination and clustering of ER-phagy receptors controls the multistep process of ER-phagy and membrane remodelling. We aim for a comprehensive understanding of the distinct mechanisms involved in ER remodelling in different cell types and in response to various stress conditions. This mechanistic knowledge is essential to explain how changes in ER-phagy and ER remodelling impact on the pathophysiology of human diseases from bacterial infections to neurological disorders. These novel and ground-breaking discoveries will elucidate an ER-phagy receptor code controlling ER remodelling in health and disease. Moreover, ER-REMODEL will provide a conceptual framework for future studies into the dynamic regulation of other cellular organelles via ubiquitin-driven selective autophagy.

Mots-clés : er phagy,er remodelling,er stress,cellular homeostasis,reticulons,reticulon homology domain,ubiquitination,membrane dynamics,autophagy,neurodegeneration,legionella,molecular simulations,disease modelling,qproteomics,cell biology,post translational modifications,structural biology,receptor clustering
Projet ERC : OUTSMART-infection (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Technion - Institut de technologie d'Israël — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Antibiotics are a double-edged sword: they help clear the current infection, yet can also select for resistant pathogens, making future infections harder to treat. While treatment guidelines recognize this ‘collateral damage’, we currently lack strategies to predict how treatments affect future recurrence and resistance at the individual patient level. This problem is of particular importance in Urinary Tract Infections (UTIs); affecting the majority of women over their lifetime, UTIs can chronically recur despite antimicrobial treatment. Importantly, UTIs are often self-seeded by strains residing in the gut microbiome, suggesting that the gut microbiome may provide means to predict current and future infections and could possibly even be manipulated to minimize infections. Here, we propose an interdisciplinary approach combining high-throughput phenotyping and genomics of same-patient gut-microbiome and UTI samples with machine-learning analysis of clinical records, towards a “look-ahead” treatment strategy for recurrent infections. First, we will use whole-genome and meta-genome approaches to sensitively detect infecting strains within the patient’s microbiome and develop a gene-based model for the infectivity of strains and thereby for the likely infecting agent and resistance profile of infection. Second, we will use long-read sequencing to map genetic linkage among resistances in each patient’s microbiome, enabling the development of a reinforcement machine-learning model to assign treatments that minimize both the risk of treatment failure and of future resistance. Finally, quantifying in vivo and in vitro the impacts of antibiotic intake on microbiome composition, we will test the feasibility of prescribing antibiotics that manipulate the microbiome in favor of less infectious strains. Together, this unique research-to-clinic data-rich approach will establish the basic foundations for a microbiome-based paradigm of look-ahead treatment strategies.

Mots-clés : genomics,antibiotics,antibiotic resistance,microbiome,gut microbiome,infections,urinary tract infections,electronic health records,personalized medicine,machine learning,digital health,pathogens,enterobacteriaceae
Projet ERC : JuvenTwin (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and Processes Engineering
Entité participante : Institut Mines-Télécom — Pays : France — Rôle : PI
Acronyme de l'entité : IMT
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2435688.0 €

Whilst 30% of EU citizens will be over 65 and 10% over 80 by 2050, the healthspan accounts for only 80% of the total life expectancy according to Eurostat, due to the high prevalence of disabling diseases related to the age-induced arterial stiffening. The current paradigm in medicine is to palliate these diseases with sophisticated devices. In JuvenTwin, I propose a complete shift of paradigm by combatting the mechanobiological effects of vascular ageing. Vascular rejuvenation faces many challenges that have only been explored by molecular biologists. My ambition is to address these challenges with a high-risk approach relying on multiscale digital twins and enabling to simulate and screen effective rejuvenation treatments. My hypothesis, already supported by preliminary results, is that this can be achieved by doping the synergistic effects of mechano-regulation in human arteries, which are gradually compromised with vascular ageing. JuvenTwin’s four specific objectives are: 1/ Decipher how ageing affects cell phenotypes and the signalling pathways of mechano-regulation, 2/ Assess the effects of ageing on the mechanical interactions between cells and their matrix, 3/ Simulate computationally the multiscale synergies participating to patient-specific vascular mechano-regulation and finally 4/ Take the control of mechanobiology in aged arteries using small molecule inhibitors and cell mechanical stimulations. With my team, we will reach these objectives by developing two completely novel methodologies: a 4D high-resolution strain mapper and a micromechanical computational model simulating the dynamical interactions of 100,000 vascular cells in patient-specific arteries. Our interdisciplinary approach combining digital spatial transcriptomics, laser interferometry and neural networks will be of very high-gain for discovering therapies against the adverse mechanobiological effects of vascular ageing, potentially reaching the pre-clinical stage at the horizon 2030.

Mots-clés : multiscale computational model,digital twin,vascular aging,spatial transcriptomics,physics informed neural network,high resolution laser interferometry,focal adhesion dynamics,rejuvenation
Projet ERC : DIVISION (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : BI Norwegian Business School — Pays : Norvège — Rôle : PI
Acronyme de l'entité : BI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2277400.0 €

The division of labor - breaking down work into tasks so that workers can specialize in a subset of tasks - is believed by many economists to be key to economic progress, by providing efficiency gains when producing goods and services. A key feature of the modern economy is that the division of labor is increasingly taking place between firms - in a production network - as firms fragment production along the supply chain, both within and across borders (Johnson and Noguera, 2017). This project aims to provide new frameworks and novel evidence on how deepening production networks shapes the division of labor within and across countries, with particular emphasis on labor market implications of production networks. Specifically, DIVISION will investigate how production networks jointly shape efficiency and equity: What are the economic effects of deepening production networks on efficiency, specialization and growth? And what are the effect on wages, the skill premium (skilled relative to unskilled wages) and earnings inequality? This comprehensive and ambitious analysis includes developing new methods and economic frameworks as well as providing new datasets and novel empirical evidence. Economic growth has slowed down since the 2007-08 global financial crisis, European firms are getting older and less dynamic and economic inequality is increasing in many parts of the world. A rigorous analysis of the role of production networks for efficiency and equity is therefore urgently needed to address today’s main societal challenges.

Mots-clés : production networks,division of labor,productivity,international trade,global value chains
Projet ERC : FLOWS (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
Entité participante : Université de Groningue — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : RUG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499424.0 €

Galaxy formation is driven by the flows of gas in and out of galaxies, which remain poorly understood. Galaxies grow and fuel their star formation through the accretion of new gas, while stellar and AGN activities eject copious amount of gas into the environment. The physics of and interplay between these phenomena (cosmic baryon cycle) are extremely complex, with the consequence that our current understanding of how and when gas flows take place and their impact on the life-cycle of galaxies is still patchy.  Hence, the FLOWS ERC project is designed to precisely determine the properties of gas flows in and out of galaxies across cosmic time and explain their role in galaxy formation and evolution. With FLOWS, we will conclusively determine how gas accretion from the environment takes place and how it changes with time. We will accurately measure the properties of galactic winds and fountains and establish their role in regulating the gas content of galaxies. We will build the next generation of predictive galaxy evolution models that will include, for the first time, fully constrained gas flows.  FLOWS will achieve these ambitious goals thanks to a unique and powerful combination of innovative data analysis and theoretical investigations. My team will study gas flows in and around galaxies using the full range of state-of-the-art data coming from ALMA, the SKA pathfinders, the VLT, the HST and JWST.  Most importantly, we will design new analysis techniques, including the first 3D code to model galactic winds directly in datacubes. Ground-breaking theoretical methods will allow us to combine the benefits of large-scale models with high-resolution magneto-hydrodynamical simulations. This multifaceted approach, which is the key to crack the baryon cycle problem, derives its strength from the diverse research lines that I have pursued in the past years, which puts me in a unique position worldwide to the make the major leap forward that FLOWS promises to achieve.