Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : JUST PEN (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Université de Birmingham — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 125875.0 €

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 : METACOMP (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer Science and Informatics
Entité participante : Université d'Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2454938.0 €

One of the most fundamental questions in computer science is the P vs NP question, which asks if every computational problem with efficiently verifiable solutions is efficiently solvable. Equivalently, it asks if all propositional tautologies have proofs that can be found efficiently. The answer is widely believed to be negative, but we lack a rigorous justification for this belief. The field of computational complexity approaches P vs NP and related questions by showing lower bounds (i.e., impossibility results) on efficient computations, while the field of proof complexity approaches these questions by showing lower bounds on efficient proofs for propositional tautologies. Despite much effort, the best known lower bounds in both computational complexity and proof complexity are quite far from resolving the P vs NP question, and there are significant barriers to the success of known techniques.  In this project, we will approach fundamental lower bound questions in computational complexity and proof complexity using the recently developed conceptual framework of "meta-complexity". Meta-complexity studies the complexity of computational problems and propositional statements that are themselves about complexity, eg., the Minimum Circuit Size Problem, which asks if a given Boolean function has small Boolean circuits. Concepts and techniques from meta-complexity have been instrumental in major recent advances in theoretical cryptography and average-case complexity, overcoming known barriers. We will extend this methodology to attack some of the deepest questions in theoretical computer science, by showing new lower bounds on both proofs and computation, establishing strong connections between computational complexity and proof complexity, and giving applications to explicit constructions, learning and hardness of approximation. A key aspect of our approach is that meta-complexity is a unifying framework, which applies equally well to proofs and computation.

Mots-clés : computational complexity,proof complexity,pseudorandomness,lower bounds
Projet ERC : SpatioCoexistence (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : Helmholtz Centre for Environmental Research — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : UFZ
Type d'entité : Recherche
Financement ERC de l'entité : 2497799.0 €

Ecologists have tried for long to explain coexistence of many competing species in communities such as tropical forests, but this key question of ecological theory remains largely unresolved. We argue that this failure originates as a scaling problem. Although plants compete mostly with their closest neighbours, the phenomenological models of most approaches addressing this question do not consider spatial mechanisms of how the dynamics and patterns at the “macroscopic” community scale emerge from the collective behaviour and interactions of individuals at the “microscopic” neighbourhood scale. We therefore propose to change the way the problem is tackled by incorporating this essential information into macroscopic mathematical models.  The overarching objective of the project is to develop a spatially-explicit theory for understanding the dynamics and stability of plant communities of intermediate to high species richness at local scales. We integrate state-of-the-art mathematical and simulation approaches with methods from physics and spatial analysis of the best available spatial data, such as ForestGEO inventory data of 20-50 ha forest plots, each comprising the species identity, size and location of >100,000 trees. The link to the microscopic scale of individual plants allows us to integrate ecological detail in unprecedented ways, while keeping the theory tractable. Such a comprehensive and highly integrated research endeavour can only be tackled within the frame-work of a large project and will be a ground breaking advance at this final frontier of ecological research. The project will provide theoretical expectations and mechanistic understanding of how multiple (spatial) pattern and processes shape species richness, and reveal if simple laws govern the assembly and dynamics of complex species-rich communities. This proposal will also open the door to new research lines of spatial ecology to better understand and conserve biodiversity.

Mots-clés : computer simulation,forest dynamic model,in silicio biodiversity experiments,micro and macroscopic scales,spatial point process,stochasticity,separation of timescales,species interactions
Projet ERC : INCANTAR (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Next generation diagnostic srl — Pays : Italie — Rôle : Partner
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 50000.0 €

Transcription factors EB and E3 (TFEB and TFE3), members of the MiT-TFE family, are master controllers of lysosomal biogenesis and autophagy. The activity of TFEB and TFE3 is regulated by mechanistic Target Of Rapamycin Complex 1 (mTORC1), a central hub of cell metabolism, which inhibits their cytoplasm-to-nucleus translocation. We recently discovered that mTORC1 phosphorylates TFEB and TFE3 via a non-canonical TORC1 (NC-mTORC1) signaling mechanism, providing the first evidence that mTORC1 can produce specific responses to different environmental cues by differential substrate phosphorylation. We and others recently discovered that dysregulation of NC-mTORC1, leading to constitutive activation of TFEB/TFE3, is the main driver of the renal cystic and tumorigenic phenotype of inherited cancer syndromes Birt-Hogg-Dube' (BHD) and Tuberous Sclerosis Complex (TSC). Remarkably, deletion of TFEB completely rescued renal cystogenesis and tumorigenesis in BHD and TSC mouse models. Furthermore, additional types of cancer have been associated to induction of TFEB/TFE3, suggesting that this may be an emerging mechanism of tumorigenesis. In INCANTAR (INherited CANcer TARgeting) we aim to identify novel regulators of TFEB/TFE3 factors by CRISPR screening and protein interactome analyses, which may reveal new therapeutic targets. We also plan to thoroughly characterize the pathogenic role of TFEB and TFE3 in TSC and BHD using transgenic mice and kidney and brain organoids. Finally, we will explore novel therapeutic strategies for TFEB/TFE3 driven diseases, such as selective ablation of cells expressing GPNMB, a sensitive transcriptional target of MiT-TFE factors, and drug screening for MiT-TFE inhibitors using a newly developed MiT-TFE transcriptional reporter. These studies will shed new light on the mechanisms underlying the pathogenic role of MiT-TFE factors and are likely to generate novel therapeutic tools for several cancer-associated conditions.

Mots-clés : mtorc1,lysosome,tuberous sclerosis,autophagy,kidney cancer,cell signalling,gene networks
Projet ERC : ELECTROSOL (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
Entité participante : Université d'Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Over the last several decades, dating back to the work of Langmuir, and Rosalind Franklin, the literature has consistently reported on a long-ranged attraction between particles in solution carrying electrical charge of the same sign. This attraction is not explained by standing theories and has remained an open conundrum. My laboratory has recently made important progress in elucidating the underpinnings of this phenomenon, introducing an “electrosolvation” force that drives spontaneous attraction and cluster formation in like-charged particles in solution. The force is long-ranged and is governed by the orientation of solvent molecules at the particle-electrolyte interface. The sign of the force exhibits an asymmetric response to the sign of charge of the particle: e.g., in water, negatively charged particles counterintuitively attract, whilst positives repel as expected, and vice versa in other solvents. This fundamental and unexpected mechanistic insight now opens for the first time the possibility to systematically investigate the origins of a host of poorly understood natural processes that are likely governed by this interaction, touching virtually all areas of the life sciences and beyond. Noteworthy examples include interactions driving biomolecular condensation, pathological protein aggregation, crystallization, gelation and DNA packing. We will carry out an in-depth experimental exploration of the interaction across length scales - from molecules to microspheres and macroscopic surfaces - using cutting edge experimental methods pioneered in my laboratory. We will further advance a fundamental understanding of the interaction through theoretical modelling and simulation. This comprehensive investigation will likely lead to the establishment of a broad and generally applicable conceptual paradigm that will fundamentally redefine how we think about molecular and particle interactions in the solution phase.

Mots-clés : interparticle interactions,molecular interactions,solvation forces,non local electrostatics,biomolecular condensation
Projet ERC : Dimension (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Université d'Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499733.0 €

What am I going to do? I will use data from millions of human genomes and thousands of traits (the “phenome”) to quantify the dimension of the heritable human phenome and dissect and map it to single DNA variant resolution; use whole genome sequence data in populations and families to estimate mutational trait heritability; predict future phenotypes using millions of DNA variants and thousands of environmental factors.  Why am I going to do this? Despite the discovery of hundreds of thousands of DNA variants that are statistically associated with one or more human complex traits, we do not know which variants are causative, how many traits they affect (pleiotropy), how they function and why there is so much genetic trait variation in the first place. We understand even less of how environmental factors (the “exposome”) interact with genomic variation to cause the variation in phenotypes that we observe. What is missing is a full genome-wide characterisation of multivariate genetic architecture and estimates of genetic variation due to new mutations. A better understanding of pleiotropy, mutational variance and the exposome will inform theoretical and biological models of trait variation and improve prediction of disease in personalised medicine.  How am I going to do this? This Project will repurpose data from multiple large biobanks containing millions of genotyped and sequenced individuals who are longitudinally measured on thousands of traits. New advanced statistical approaches will be developed, tested and applied in innovative experimental paradigms that utilise both population and pedigree data. Variance component methods will be developed to estimate mutational variance. Bayesian hierarchical mixture models will be developed and applied to fine-map multivariate trait loci and to predict future disease cases. My Team will develop general user-friendly software tools to achieve the Project aims.

Mots-clés : quantitative genetics pleiotropy mutational heritability personalised medicine
Projet ERC : BactOMPbuild (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : Université d'Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2490791.75 €

Gram-negative bacteria are distinguished by the presence of an outer membrane (OM) at the cell periphery. This membrane is the site at which the bacterium interacts with its environment (or host if a pathogen), and provides the first line of defence against antibiotics, mechanical stresses, and immunological attacks. These functions depend on the presence of proteins that either span the outer membrane (Outer Membrane Proteins, or OMPs) or are anchored to the membrane by a lipid tail (lipoproteins). Sophisticated machinery is required to target, insert, and fold these proteins. Although this machinery is well-characterised in Escherichia coli and related organisms, it remains unclear how OM proteins are assembled in other major Gram-negative phyla. In this project we aim to elucidate novel features of OM protein biogenesis in bacteria of the phylum Bacteroidota (formerly Bacteroidetes). The Bacteriodota are key human commensals, but also include major anaerobic pathogens, and are environmentally abundant. The pathways for OM protein biogenesis in the Bacteroidota differ from the E. coli paradigm in at least two major ways that we will investigate.  First, we have discovered that the Bam complex that is responsible for inserting OMPs into the OM has a very different composition from the E. coli paradigm and includes novel extracellular subunits. We now seek to identify the function(s) of these additional subunits and elucidate their molecular mechanism. Second, in contrast to E. coli, the cell surface of Bacteroidota bacteria is coated with abundant lipoproteins (surface lipoproteins, or SLPs) that must be exported across the OM by a currently unknown mechanism. We aim to identify and characterise this SLP transporter as well as the novel pathway that our work has shown is needed for delivering SLPs to the OM. To carry out these tasks we will employ in vivo and in vitro protein biochemistry, bacterial genetics, and structural analysis by cryoEM.

Mots-clés : bacterial outer membrane,periplasm,bacteroidota,bacteroidetes,bam complex,surface lipoprotein biogenesis,bacteria,membrane protein biogenesis,protein transport,periplasmic chaperones,skp,tam,omp85 family
Projet ERC : TERRITORY (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
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 : 2496895.0 €

The urge to defend one’s territory is an evolutionarily conserved instinct aimed at securing optimal access to food, mates, and shelter. Conflict arises when territories become unstable due to seasonal changes in resource availability, or when population density increases. Under such conditions, individuals must carefully balance social aggression and avoidance to maximize their control of territorial resources while avoiding subordination at the hands of their neighbors. What is the neural basis of such dynamic territorial behaviors? We have found that an evolutionarily conserved medial hypothalamic brain structure serves as a switch between social aggression and avoidance. In this proposal we ask where and how is territory encoded in the brain and how could it control this hypothalamic switch? A clue emerges from recent work in which we discovered that neural activity in this structure encodes a map of social space much like the mammalian hippocampus encodes a map of navigational space. However, unlike hippocampal place cells that arise spontaneously as animals explore, hypothalamic territory cells require social experience to form. We will develop a semi-natural laboratory testing environment where we can monitor the dynamic acquisition of territories in mice over time and apply in vivo neural recording, activity perturbation, and computational modelling to extract precise synaptic integration and plasticity mechanisms that underlie territory-based decision-making in the mammalian brain. Uncovering the neural basis of territorial behaviors is an essential step toward a biological understanding of human aggression and fear and could provide insight into interventions for maladaptive responses to threats to personal space, resources, and beliefs.
Projet ERC : ZEOLIghT (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 2500000.0 €

Zeolites are a class of nanoporous crystalline inorganic materials that rank among the most versatile catalysts and are capable of facilitating the development of sustainable chemistry, separation and emerging processes. The aim of ZEOLIghT is to understand the fundamental molecular-level interactions leading to specific crystallization events of nanozeolites to direct their properties. The three challenges are: 1. rational formation of molecularly-ordered precursors with different tetrahedral (T)-atoms, understanding the fundamentals of zeolite growth kinetics in colloidal and high solid precursors resulting in frameworks with controlled defects and flexible structures (Fundamental understanding of defects and flexibility of nanozeolites), 2. translate the discovery at the atomistic scale to development of novel nanozeolites and fine-tuning of relevant properties including crystals size, pore dimension, framework structure, bulk chemistry, and stability (Engineering nanozeolites), and 3. relate the defects and flexibility as the origin of the remarkable properties of ultra-stable zeolites for applications in heterogeneous catalysis: the selection of the non-oxidative conversion of methane reaction as a specific case, but not limited to, will be considered (Application). The mysterious “defects” associated with the generation of various silanol species, Brønsted acid sites, and vacancies as integral parts of the reaction center of zeolites and their relation to the framework flexibility will be elucidated by advanced characterization. The ZEOLIghT project will be the fundamental scientific driver for seeking novel nanozeolites and fully realize the knowledge gained in global cases where porous materials are considered. The key achievements are understanding the properties of nanozeolites by uncovering the consequences of defects and flexibility. The nanozeolites will claim a sizeable share of the global zeolite market for both classical and emerging applications.

Mots-clés : zeolites,nanocrystals,defects,silanols,flexibility,kinetics,synthesis,size,pores,cages,framework,morphology,diffusion,pathlength,green synthesis,regeneration,stability,catalysis,methane,hydrogen
Projet ERC : IMPACT (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Human Technopole — Pays : Italie — Rôle : PI
Acronyme de l'entité : HT
Type d'entité : Recherche
Financement ERC de l'entité : 1893856.0 €

The extending human lifespan and its associated accumulation of morbidities due to chronic disorders calls for new models to accelerate the early detection, prognosis and treatment of chronic conditions. To date, anchoring detailed molecular knowledge of disease processes with diagnoses of chronic diseases from ‘real-world’ biomedical data remains an open challenge.The immune system plays a central role in human health and survival, while deterioration of immune function is implicated in the development of many devastating chronic conditions. While many aspects of immune functions have been studied in exquisite molecular detail, we still lack a comprehensive understanding of how lifestyle factors, environmental exposures and biology contribute to deterioration of immune functions during the human life-course, and consequently to risk of disease as individuals age. With this project we propose a new research paradigm to study chronic human diseases by combining the power of single-cell technologies with multimodal information of health states and genomics derived in large-scale population settings. In Objective 1, we will use state of the art statistical modelling on a world-unique dataset of 12M peripheral blood mononuclear cells (PBMCs) generated by my group. We will combine immunological states with data from health records to discover cell states associated with markers of normal ageing processes, diverse disease diagnoses and environmental exposures. In Objective 2, we will use multimodal profiling and ex vivo experiments to validate genes and networks associated with disease-relevant cell state variation. In Objective 3, we will apply this new knowledge to predict the long-term risk of disease in diverse population settings. Overall, this project promises to add a fundamental new perspective to our understanding of the dynamic changes of the immune system over the human adult lifecourse, and its interaction with health and disease states.

Mots-clés : causal inference single cell biomedical records health data genetics population studies age related chronic diseases disease prevention cellular programmes gene networks