Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : CLAMP (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Conseil supérieur de la recherche scientifique — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 2497271.0 €

Multi-drug resistant (MDR) bacterial infections threaten all the advances in modern medicine after the industry nearly abandoned antibiotic development and no mechanism to suppress antibiotic resistance has been found. However, our results indicate that this mechanism does exist and is conserved in functional membrane microdomains (FMM) in all prokaryotes. We discovered bacterial FMM, akin to eukaryotic lipid rafts, and demonstrated their crucial role in preserving proteins correctly folded at no ATP cost. FMM are essential for pathogens survival during infections thus, FMM perturbation causes the bacterial proteome to collapse, particularly affecting heterologous proteins responsible for MDR. This leads to attenuated infections and additionally re-sensitizing MDR pathogens to antibiotics. Studying FMM will transform our understanding of cellular membrane organization and its connection to protein misfolding disorders. Accordingly, this proposal will undertake an ambitious molecular characterization of FMM and its impact on bacterial proteostasis, and we will apply this knowledge to bring closer to the clinic a battery of anti-FMM drugs that target FMM to reactivate antibiotics against MDR infections. To achieve this, a first structural goal will describe FMM molecular organization, how FMM operate to prevent protein misfolding, and the molecular principles driving the assembly of membrane microdomains in cells. Secondly, a functional goal will describe the mechanism of proteome stabilization independent of ATP and its crucial role in pathogenesis. Finally, an applied goal will be to implement anti-FMM drugs to eliminate MDR infections and re-sensitize them to conventional antibiotics. This proposal unveils a new frontier in understanding the cellular programs for membrane compartmentalization, their connection to protein-misfolding cellular dysfunction, and the possibility of applying this knowledge to revitalize classical antibiotics against MDR infections.

Mots-clés : staphylococcus aureus,bacterial membrane,membrane microdomains,protein misfolding,proteostasis,multi drug resistance
Projet ERC : SPONTSENSE (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Conseil supérieur de la recherche scientifique — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 1980290.0 €

It is commonly held that spontaneous activity in the immature brain prepares the neural circuits to process sensory information at the onset of experience. The best studied patterns of such activity are those observed postnatally in rodents, during stages that resemble the last months of gestation in humans. However, the features and functions of spontaneous activity at earlier stages, when the brain’s foundations are laid down and cortical areal identities are acquired, remain largely unknown. Here, I propose to develop an extensive and creative research program aimed at understanding the role of the patterns of spontaneous activity in the specification of sensory cortices and long-term plasticity. This novel line of research is founded on strong preliminary results and pursues the hypothesis that different cortical sensory territories exhibit unique patterns of spontaneous activity that interact with emerging area-specific transcriptional programs to specify sensory areas functionally. We will first extract the earliest patterns of spontaneous activity from cortical and subcortical territories in embryonic and perinatal mice in vivo and study their concurrent spatiotemporal genetic signatures by single-cell transcriptomics. Next, we will perturb these early activity patterns within a specific sensory modality to reveal if such perturbation modifies the genetic landscape and affects sensory identity. Finally, we will evaluate the behavioural consequences of functional cortical re-specification in adult mice. SPONTSENSE will set the stage to understand the principles of sensory circuit development and shed new light on the brain plasticity following sensory defects. I envisage that this information will pave the way to devise strategies that may serve to direct these programs of plasticity in clinical situations as when sensory input has been compromised.

Mots-clés : spontaneous activity,meso scale calcium imaging,scrnaseq,transgenic mice,sensory cortices,thalamus,sensory behaviour
Projet ERC : HAPI (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and Processes Engineering
Entité participante : Université catholique de Louvain — Pays : Belgique — Rôle : PI
Acronyme de l'entité : UCL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

The design of critical structural metallic components in the aeronautic, biomedical, nuclear or pipeline fields is often dictated by a fail-safe criterion established in the context of fracture mechanics. The design must prevent any pre-existing crack to propagate under nominal but also sometimes accidental loads. In this context, the primary material property is the fracture toughness quantifying the resistance to crack initiation. In ductile metals, the fracture toughness depends on plate thickness with a peak value attained at an intermediate thickness in the range of a fraction of a millimetre up to ten millimetres or more. Although this thickness dependence is known since the 60’s, the literature is very silent regarding the peak fracture toughness value, about what sets its magnitude and about the corresponding optimum thickness. Hence, there is no definitive rational about how to use or account for such an optimum fracture toughness in structural design. The vision of HAPI is that the fracture resistance of critical metallic structural components can be significantly enhanced by selecting and/or controlling the plate thickness for thin-walled applications and the constituent plate thickness for thick laminates. In particular, metal laminates with optimum thickness of the constituents, selected for their high strain hardening capacity will lead to unattained levels of cracking resistance. This will require generating a range of new experimental fracture data, performing complex 3D finite element simulations relying on a rich micromechanical model with new enhancements, extending the materials selection approach, exploring the processing/assembling of novel ultra-tough metal laminates up to a radically new concept of laminate pressure vessel. Major gains are expected on the weight of structures, potentially up to a factor five if fracture toughness is the dominating design factor, and this, without changing the chemistry or inventing new microstructures.

Mots-clés : fracture of materials,damage,fracture toughness,mechanical testing,materials selection,cracking,strain hardening,plasticity,metallic alloys,laminates,micromechanics,assembly
Projet ERC : OCULIS (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
Entité participante : Université de Leyde — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2457977.93 €

The current standard model of cosmology successfully describes a variety of measurements, but its main ingredients, dark matter and dark energy, are a great mystery. ESA’s Euclid satellite is the biggest step forward towards solving this fundamental problem in physics. It is designed to reveal the nature of the dark constituents and gravity by measuring the growth of structure over most of cosmic time with unprecedented precision, but the interpretation of the data is complex: incorrect modelling of the galaxy populations, astrophysical processes or instrumental effects can easily be mistaken as evidence for new physics. To fully exploit the statistical power of Euclid, the intricacies of the data need to be understood, but we also need an accurate model of structure formation that can describe the interplay between galaxy formation, astrophysics, dark matter and cosmology.  OCULIS tackles both aspects by providing the best measurements of the lensing signal and using the Euclid data in novel ways to relate observed galaxy properties directly to the matter distribution. To do so, we will (i) use in-flight data to correct for instrumental biases; (ii) measure the intrinsic alignments of galaxies that contaminate the lensing signal; (iii) exploit Euclid’s unique ability to determine the lensing signal on small scales to directly determine the stellar masses of galaxies for the first time, and to study the tidal stripping of dark matter halos; (iv) use the results to inform models that describe the small-scale astrophysics in hydrodynamic simulations, yielding robust predictions of the cosmological signals. As cosmology coordinator of the Euclid mission, the PI is uniquely positioned to achieve these objectives. The synergetic approach of OCULIS exploits that Euclid is much more than a cosmology mission: it is also a prime dataset for the study of the formation and evolution of galaxies. By linking both science cases, OCULIS maximizes the scientific return of Euclid.
Projet ERC : MIGJUST (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Université de Gand — Pays : Belgique — Rôle : PI
Acronyme de l'entité : UGent
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499812.5 €

MIGJUST addresses the unacknowledged, fundamental conflict between the European Court of Human Rights, which in its migration case law adopts a sovereignty approach normalising sedentarism, and the Inter-American and African human rights Commission and Court which adopt a human rights approach normalising mobility. This fragmentation of international law also plays out in UN human rights Committees. This fragmentation is not acknowledged in academic work, in which the European approach is assumed to represent the most advanced version of international law. This fragmentation is problematic because it undermines the international character of international law. Legal doctrine overlaps with political theory on migration justice, which focuses on Europe and North America, and does not acknowledge distinct positions developed in Latin American, African and Islamic political theory.  MIGJUST ends the hypothesised bias not merely by including Inter-American, African and UN case law and acknowledging their distinct positions; but by in addition linking European, Inter-American, African and UN case law to political theory. MIGJUST will thus produce - a restatement of international human rights law doctrine in the field of migration which includes Inter-American, African and UN case law as well as European case law; - an analysis of the conflicting fundamental positions; - an analysis of how the conflict relates to divergent ideas on migration justice in European, North American, Latino, African and Islamic political theory; - legal doctrinal alternatives, inspired by non-ideal political and legal theory.  In doing so, MIGJUST makes - a fundamental academic contribution by ending the assumed European bias; - a fundamental contribution to legal practice by unlocking Inter-American, African and UN case law; - a fundamental contribution to international cooperation between states, IOs and INGOs by making their varying normative positions understandable to each other.

Mots-clés : migration law
Projet ERC : POLY-DESIGN (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and Processes Engineering
Entité participante : Université de Gand — Pays : Belgique — Rôle : PI
Acronyme de l'entité : UGent
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2496000.0 €

A challenge in the polymer industry is the design of molecular and morphological properties along the whole production chain, minimizing energy consumption and product heterogeneity, and ensuring recyclability. Ideally, we need to track the compositional/topological variations and interactions of individual species during (i) synthesis, hence, the polymer reaction engineering (PRE) stage; and (ii) downstream final material shaping, hence, the polymer processing (PP) stage (e.g. (reactive) extrusion).  Today, the connection between the PRE and PP stage is weak and monodirectional, with only average, not distributed, ballpark PRE characteristics inputted in PP optimization. Both stages although share common bottlenecks such as micro-scale viscosity changes, meso-scale mixing limitations, and macro-scale concentration/temperature gradients.  POLY-DESIGN aims at next-generation polymer performance intensification and functionality design by a generic PRE-PP multi-scale modelling tool, tracking all changes at all length scales during synthesis and processing. This ambitious approach interactively connecting PRE and PP can tackle complex demanding products, and cost efficiently produced goods that will drive the commodity and high-tech polymer market.  A validated PRE multi-scale modelling tool is applied to access all distributed PRE characteristics, uniquely for (i) linear and branched/crosslinked (co)polymers; (i) lab and commercial polymers; and (iii) pure polymers and their blends. The polymer (blend) viscoelasticity is calculated with a multi-scale PP modelling tool at any PP shear rate and temperature for any set of PRE characteristics. In this way, an industrial PP unit can be designed from the chemical to the material level and reversely thanks to a flexible PRE-PP connection. Demonstrator cases are included for more sustainable and higher quality manufacturing of virgin and recycled polymers, benefiting from design in the PRE or PP stage, or both.

Mots-clés : polymer reaction engineering polymer processing model based design reactive extrusion
Projet ERC : HeMAFA (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Université de Göteborg — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499993.0 €

The basic research problem: Gradual loss of bone and muscle mass with ageing leads to increased risk of fractures in the elderly population. There is a large medical need for new fracture preventive therapies with minimal side effects and novel biomarkers that improve the prediction of fracture risk. The aim of the proposed research is to test our hypothesis that the increased fracture risk in elderly people is caused by an age-dependent unhealthy change of the gut microbiota (GM) composition, resulting in reduced bone and muscle mass, and thereby increased fracture risk. Methodology: We will identify age-dependent GM signatures that are causally associated with reduced bone and muscle mass and thereby increased fracture risk in elderly subjects. A major emphasis will be to determine causality of the GM using a variety of recently developed GM-related genetic instruments (for GM composition and function as well as for circulating metabolites) as exposures in 2-sample Mendelian randomization (MR). In addition, we will use faecal microbiota transplantation (FMT) to directly determine causality of age-dependent GM alterations for reductions in bone and muscle mass. Based on this information, we will design candidate probiotic treatments and test their efficacy in mouse osteoporosis models. Finally, we will determine the clinical usefulness of the identified GM signatures for fracture prediction in elderly subjects.  Research progress beyond the state of the art: We will employ three complementary methods, 2-sample MR, FMT, and treatment studies, to determine causality for GM on musculoskeletal parameters. For this research, we have established large well-characterized Nordic cohorts with metagenome sequence data and information on incident fractures available in 2023. Identification of a GM-signature with a robust effect on age-related bone and muscle loss will open-up completely new avenues to avoid fractures in elderly.

Mots-clés : fracture,mendelian randomization,ageing,gut microbiota
Projet ERC : POLICE-PRISONS-FIRMS (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : Université de Göteborg — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1625854.75 €

Economic inequality across the population implies vastly unequal opportunities in many dimensions that can impact an individual’s chance of entering the justice system. One such channel via which this can occur – even holding criminal behavior constant – is unequal treatment by agents of the justice system (e.g. police). The consequences of such partiality is not trivial: once in the system, it is hard to get out. And to the extent that convictions and sanctions result in worse outcomes (e.g. employment) for offenders and/or family members, the cycle of crime and economic inequality will perpetuate for current and future generations. This program pushes forward the evidence base on three channels (police, prisons, firms) through which this cycle can be broken. Part 1 aims to measure and study the adoption of implicit bias training programs by police agencies. Despite such programs being a go-to response of agencies accused of bias, there is almost no knowledge on how/whether they impact officer behavior. Part 2 addresses the knowledge gap on ‘what (specifically) works’ in prison. First, we will study the unintended impacts of two Swedish sanction reforms onto untreated populations. (i) Does more time in prison have spill-over effects for family members? (ii) Did the introduction of electronic monitoring impact the conditions and outcomes of ineligible offenders left behind in prison? Second, we will open the black-box of prison healthcare to study how in-prison treatment (diagnoses, medication, vaccines, programs) impacts post-release health, medication adherence, and crime.  Part 3 aims to further our understanding of the employment opportunities – or lack thereof – for workers with criminal records (WCR). We will use Swedish registers to study (i) the extent to which WCR are sorted across firms and the determinants of a firm’s demand for WCR, (ii) selection of WCR into self-employment, and (iii) how an offender’s social networks impact firm hiring decisions.

Mots-clés : inequality,discrimination,police,prisons,crime,firms,employment,health,spill overs
Projet ERC : ForCUTT (Horizon Europe, appel 2021, Advanced grants)
Entité participante : Université de Göteborg — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499776.0 €

There has been in the past 15 years remarkable achievements in the field of interactive theorem proving, both for checking complex software and checking non trivial mathematical proofs. For software correctness, X. Leroy (INRIA and College de France) has been leading since 2006 the CompCert project, with a fully verified C compiler. For mathematical proofs, these systems could handle complex arguments, such as the proof of the 4 color theorem or the formal proof of Feit-Thompson Theorem More recently, the Xena project, lead by K. Buzzard, is developing a large library of mathematical facts, and has been able to help the mathematician P. Scholze (field medalist 2018) to check a highly non trivial proof.  All these examples have been carried out in systems based on the formalism of dependent type theory, and on early work of the PI. In parallel to these works, also around 15 years ago, a remarkable and unexpected correspondance was discovered between this formalism and the abstract study of homotopy theory and higher categorical structures. A special year 2012-2013 at the Institute of Advance Study (Princeton) was organised by the late V. Voevodsky (field medalist 2002, Princeton), S. Awodey (CMU) and the PI. Preliminary results indicate that this research direction is productive, both for the understanding of dependent type systems and higher category theory, and suggest several crucial open questions. The objective of this proposal is to analyse these questions, with the ultimate goal of formulating a new way to look at mathematical objects and potentially a new foundation of mathematics. This could in turn be crucial for the design of future proof systems able to handle complex highly modular software systems and mathematical proofs.

Mots-clés : type theory,interactive theorem proof systems,axiom of univalence,constructive mathematics
Projet ERC : NextReason (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer Science and Informatics
Entité participante : Université de Göteborg — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Galileo said that mathematics is the language of science. It is used to solve arbitrary abstract problems, underpinning hard sciences, technology and engineering. Automation of complex mathematical reasoning, discovery and large-scale formal proofs is today one of the greatest challenges in the fields of Automated Reasoning (AR) and Artificial Intelligence (AI). Compared to human experts, today’s main automated reasoning and theorem proving paradigms are severely one-sided: they largely lack the capability to combine learning, reasoning and conjecturing in complex feedback loops. There is solid evidence that such combinations are the key to building the next generation of advanced reasoning systems for mathematics, computer-assisted proof and formal verification.  The NextReason project will create one of the world’s strongest teams working on such combinations. We will jointly develop (i) logic-aware learning architectures and neuro-symbolic methods for a range of automated and interactive theorem proving paradigms, (ii) novel AI approaches for learning-guided automated decomposition of hard reasoning problems, (iii) methods for automated formalization of human-written mathematics by combining learning-based translation methods with semantic methods such as type-checking and theorem proving, (iv) neuro-symbolic methods for synthesis of interesting mathematical objects, conjectures and explanations, and (v) autonomous systems and positive feedback loops interleaving learning, theory exploration and efficiently guided proof search to attack hard and open problems.  The expected overall outcome is a new generation of strong architectures for reasoning and theorem proving, and their transformative effect on large-scale computer-assisted proof, mathematics and formal verification.

Mots-clés : automated reasoning,automated theorem proving,interactive theorem proving,formal proof,automating mathematics,formalized mathematics,ai and theorem proving