Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : SWItchFate (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Institute of Molecular Biology — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : IMB
Type d'entité : Recherche
Financement ERC de l'entité : 2009474.0 €

The mammalian SWI/SNF chromatin remodellers, the BAF complexes, are critical regulators of gene expression by modulating the accessibility of regulatory regions, especially of cell identity genes. Their importance for cellular maintenance and differentiation is emphasised by the fact that they are frequently associated with disease. Mutations in genes encoding BAF subunits are found in over 20% of cancers and are causative for neurodevelopmental disorders (NDD). The prevalence for specific NDD with unique clinical features depends on the mutant subunit. The molecular changes leading to the disease phenotypes are largely unresolved. The functions of BAF complexes and specific subunits during human brain development are also still unclear. SWItchFate thus aims to systematically identify the role of individual BAF subunits and their mutations in brain development and abnormalities. To this end, isogenic wild type, mutant and engineered human induced pluripotent stem cell (hiPSC)-derived cerebral organoids will be used in combination with various bulk and single-cell epigenomics and proteomics tools. SWItchFate will investigate gene regulatory mechanisms altered during brain development with CRISPR/Cas-based loss-of-function screens for all BAF subunits. Using protein degradation tools targeting specific BAF subunits, SWItchFate will pinpoint vulnerable processes and adaptation mechanisms. In addition, cell type- and BAF subtype-specific composition, interaction partners and target sites along brain development will be mapped to decipher BAF-dependent gene regulatory networks. Finally, the molecular changes in BAF mutation-induced NDD that cause the phenotypic changes in patients will be examined and conserved mechanisms across different genotypes will be deciphered using patient-derived hiPSC. Thus, SWItchFate will decode the regulatory functions of BAF complexes in the context of cell fate decisions in development and disease, paving the way for new therapeutics.

Mots-clés : brain development,cerebral organoids,neurodevelopmental disorders,baf complexes,swi snf,chromatin remodelling,cell fate control
Projet ERC : FINE-TEA-SQUAD (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental Constituents of Matter
Entité participante : Université de Leyde — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1485042.5 €

Quantum technologies have set remarkable milestones in the last years, e.g. with quantum advantage experiments and loophole-free Bell tests. Despite this progress, the quantum devices we currently have, the so-called noisy, intermediate-scale quantum (NISQ) devices, are too imperfect to run textbook quantum algorithms, yet they hold great potential. With their advent, much research has been devoted to finding them a first practical application. Focus on optimization, quantum chemistry and machine learning has been intense, and the developments are closely monitored by governments and industry alike. Variational algorithms in a classical-quantum feedback loop and adiabatic algorithms have been the dominant paradigm. However, important bottle-necks remain that severely maim the performance of NISQ devices and the field yearns for a novel approach. FINE-TEA-SQUAD, FIrst NEar-TErm ApplicationS of QUAntum Devices, proposes a radically new vision: to develop a unifying framework that will yield the first practical applications of NISQ devices. The main objectives are (A) to design experimentally-friendly protocols for quantum state preparation circumventing major existing bottlenecks (high number of repetitions, noise-induced barren plateaus...) and characterize broad families of states that can be prepared in a scalable way, (B) to develop a practical certification toolset amenable to near-term devices, with especial focus on the generation of certified randomness from a single NISQ device. The key idea is to use the hardness of many-body physics in a classical verifier-quantum prover interactive protocol. This approach will overcome the existing limitations of current approaches: it will be both easy to prepare and easy to verify (C) to overcome current hardware scalability limitations by combining several NISQ nodes into a small quantum network, and develop the appropriate theoretical framework to efficiently tailor and run quantum algorithms on them.

Mots-clés : near term quantum architectures,device independent,quantum information processing,certified randomness generation,tensor networks,variational algorithms,adiabatic algorithms,distributed quantum computing,semidefinite programming,certificates,relaxation methods
Projet ERC : CLOSEtoQG (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental Constituents of Matter
Entité participante : Université de Leyde — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2445909.0 €

This proposal addresses one of the key challenges of modern physics: understanding the interface between quantum mechanics and general relativity. Recently, an experimental test was proposed that can directly witness the need to unify the two theories: observing quantum entanglement between objects that only interact through the gravitational field. A successful test would prove the existence of superpositions of space-time and have far-reaching implications on how we understand our world.  So far, no experimental platform exists that can meet the challenging central requirement for this test: A picogram-scale mass in a micrometre-scale spatial superposition with a second-scale coherence time. Here I propose to build such a platform.  The objectives of the research are to trap and levitate a picogram mass, cool its centre-of-mass motion to the quantum ground state, couple its motion to a controllable qubit system and, finally, produce and measure a spatial superposition of the mass.  Considering all requirements, I identify the unique combination of techniques necessary to achieve this: - diamagnetic levitation at cryogenic temperatures using on-chip superconducting coils; - on-chip superconducting quantum interference device (SQUID)-resonator based sideband cooling; - coupling to solid-state spin qubits.  Combining recent microfabrication techniques for chip-based confinement of micro-particles, high-Q resonant circuits and microscopic diamond membranes with spins, it is now possible to realize this system in the lab. My extensive experience with spins and nanomechanical systems as well as microfabrication and low-noise cryogenic measurements, and Leiden University?s infrastructure for vibration-isolated cryogenics supports CLOSEtoQG?s objectives.  The research would represent a major step towards a spin-based entanglement witness of quantum gravity. Moreover, each sub-objective can benefit applications in force sensing and magnetic resonance force microscopy.

Mots-clés : quantum gravity,levitation,entanglement,spin qubits,optomechanics,quantum foundations,force sensing,
Projet ERC : MicroT (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : University Hospital Schleswig-Holstein — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : UKSH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

The microbiota has an enormous influence on human health. CD4+ T cells play a central role in controlling the interaction with the microbiota. By specifically reacting against individual microbial species, T cells enable a mutualistic co-existence with microbes. Inappropriate T cell responses against microbes are in turn associated with inflammatory diseases. Thus, the combination of T cell specificity and functionality form the key determinant for physiological versus pathological host-microbiota interactions. So far, research on T cell-microbiota interaction is almost exclusively focussed on functional T cell subsets, whereas antigen-specificity is rarely addressed. This is a significant roadblock for developing targeted therapeutic interventions for microbiota-associated diseases. The interaction with the microbiota poses two particular challenges for adaptive immunity: first, the extremely high diversity of microbial species, and thus potential T cell targets; second, microbes are persistent and thus probably encountered chronically. Currently, we do not know (1) which microbes are targets of specific T cell reactivity in humans, (2) how the (chronic) interaction with the huge number of different microbial species is regulated by T cell specificity and function, and (3) how alterations of these parameters contribute to microbiota-associated diseases. I developed a highly sensitive technology to detect and deeply characterize microbe-specific T cells directly from human samples. MicroT will identify microbial target species of human T cells and unravel the molecular mechanisms regulating chronic interaction of T cells with the highly diverse microbiota. I will define the impact of specific T cell-microbiota interactions on chronic inflammatory diseases and upon ageing. Answering these fundamental questions of microbiota-T cell interaction will identify specific immune or microbial targets as an essential basis for rational development of novel targeted therapies.

Mots-clés : antigen specific cd4 t cells t cell microbiome interaction t cell cross reactivity regulation of microbe reactive t cells
Projet ERC : METATARGET (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Essen University Hospital — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1493750.0 €

Metastasis is responsible for over 90% of deaths that occur in patients with cancer. So far there are no therapies that precisely target a metastatic disease due to the limited number of efficient druggable targets. Recently, I discovered in melanoma: circulating tumor cells are depending on arginine for their survival. In addition, I revealed that liver metastases specifically upregulate their alanine metabolism during metastasis. Thus, metastatic cells at different stages have dependencies on unique amino acids (AA). While most research focuses on the primary stage, my proposal will focus on the missing gap aiming to prevent metastases formation. Based on these new paradigm-changing discoveries, I hypothesize that metastatic cells modulate their AA metabolism during metastatic progression, and targeting the unique AA dependencies will decrease their survival and metastatic potential. Using sophisticated in vivo metastasis assays both in mouse and in patient, cutting-edge mass spectrometry and in vivo isotope tracing technologies, I will identify metastasis-specific inhibitors by investigating the following questions. I. How does arginine support melanoma cell survival in circulation? By using metabolomics, stable isotope tracer analysis and transplantation assays both in mouse and human, I will uncover how we can use this unique AA dependency of CTCs as a novel target. II.How does metabolic heterogeneity in the circulating tumor cells support organotropism? To mechanically dissect metastatic organotropism, I will map metabolic differences in melanoma metastases and also examine how we can target alanine metabolism to block metastases. The understanding of AA adaptation of cancer cells is essential for the prevention of metastasis. My results will reveal new metabolic pathways that are required by metastasizing cells in vivo and therefore will fundamentally advance the ability to develop new targeted therapies for preventing early and late-stage metastatic cancer.

Mots-clés : cancer metabolism,cancer metastasis,melanoma,amino acids
Projet ERC : CRETE (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer Science and Informatics
Entité participante : Madrid Institute for Advanced Studies — Pays : Espagne — Rôle : PI
Acronyme de l'entité : IMDEA
Type d'entité : Recherche
Financement ERC de l'entité : 1500000.0 €

Refinement types are a type-based, static verification technique designed to be practical. They enrich the types of an existing programming language with logical predicates to specify program properties and automatically validate these specifications using SMT solvers. Refinement types are a promising verification technology that in the last decade has spread to mainstream languages (e.g., Haskell, C, Ruby, Scala, and the ML-family) to verify sophisticated properties of real world applications, e.g., safety of cryptographic protocols, memory and resource usage, and web security. The weakness of refinement types is that they do not meet the soundness standards set by theorem provers. A sound verification system accepts as safe only those programs that never violate their specifications. Refinement type checkers (e.g., Liquid Haskell, F*, and Stainless) approximately report five unsoundness bugs per year, as opposed to only one reported by the Coq theorem prover. This rarity of unsoundness bugs in Coq is unsurprising since Coq is designed to soundly machine check mathematical proofs. Coq's soundness design recipe though cannot be directly applied to refinement type checkers that aim to practically verify real world programs. The goal of CRETE is to design a sound and practical refinement type system.  This is an ambitious goal that entails the development of a verification system that is as practical as refinement types and constructs machine-checked mathematical proofs. The system will be implemented on refinement type systems for mainstream languages (i.e., Haskell and Rust) and will be evaluated on real-world code, such as web applications and cryptographic protocols. CRETE is high-risk since it aims to develop a novel program logic in which SMT automation co-exists with real world programming. Yet, CRETE is high-gain since it proposes a low-cost, high-profit approach to formal verification that aims to be integrated in mainstream software development.

Mots-clés : refinement types,type systems,smt program verification
Projet ERC : SignalHet (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
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 : 1499494.0 €

G Protein Coupled Receptors (GPCRs) are key mediators of how cells sense and react to their outside environment. Traditionally, these receptors have been thought to function as individual units at the cell surface. Over the past decade, new evidence has shown they can assemble in larger complexes to form new signaling entities and vastly expand a cell’s capacity to respond to its environment. Thanks to their strong tissue-specificity, these complexes -termed heteromer- also form important targets for the development of new drugs with less side effects. Still, our understanding of the molecular mechanisms by which assembly of GPCRs in complexes transform their signaling properties remain extremely sparse. My proposal investigates how heteromers interact and integrate changes in their environments to generate unique cellular responses. I focus my research on the mGlu2-5HT2A heteromer, as its existence has been demonstrated in humans and is involved in schizophrenia, a debilitating condition that urgently requires new treatments. This proposal is organised in three objectives: 1/ A too often over-looked component of a GPCR environment is the lipidic membrane it is inserted in. Using a multi-scale biophysics approach, I will characterise the essential role lipids play in the assembly and function of heteromers, but also how receptors themselves change the membrane they are inserted in to transmit information. 2/ I will use cryo-electron microscopy to solve the first structure of a heteromer, bound to its signaling partners, G proteins. I will go even further and develop cutting-edge EM tools to resolve a high-resolution movie of a GPCR heteromer signaling cascade, from receptor assembly to G protein activation. 3/ Finally, using single particle cryoEM and fluorescence, I will investigate how heteromers recruit other partners which in turn modify receptors to form these new signaling units.

Mots-clés : gpcrs,cryoem,fluorescence
Projet ERC : LangPro (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Study of the Human Past
Entité participante : Université de Leyde — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499996.0 €

Historians have shown that the period from 1550 to 1650 was marked by a rapid expanse of the print industry, language education, and administrative bureaucracy, especially in North-West Europe. This implies that there must have been a swift increase in occupational opportunities for men and women who possessed language skills such as reading, writing, and text editing in one or more languages. However, since language professionals have never been studied as a separate category in the early modern workforce, the opportunities that existed for linguistically skilled individuals remain a big unknown.  LangPro adds a fundamental missing perspective to our understanding of the early modern labour market by introducing the new notion of the language sector: that part of early modern economies which relied primarily on language skills. The project considers language proficiency as a hard skill with real-world professional value.  LangPro’s central research question is: What professional, financial, and social opportunities did the early modern language sector offer to men and women in early modern North-West Europe (1550-1650)? Five work packages will disclose the potential for personal advancement that the language industry offered: financial income; support through a guild system; enhanced social status; and job opportunities, specifically for women. Laying the groundwork for a new research domain on the history of the language sector, we will develop a conceptual framework and prosopographical database that make it possible to gain insight into the characteristics of professionals in the past whose core business was language and the nature of the sector that employed them. LangPro will evoke important shifts in the history of early modern labour, women’s history, and the history of language practices. It is the forerunner of a new research line on a long underestimated sector that provided precious opportunities to individuals from all walks of life.

Mots-clés : language sector language professionals language skills multilingualism literacy early modern period north west europe labour history language history women s history guilds
Projet ERC : FATRESCON (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université des technologies de Brno — Pays : Rép. Tchèque — Rôle : CO-PI
Acronyme de l'entité : VUT
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2496158.75 €

The necessity to meet the rising global demand for mobility and energy supply and, at the same time, the urgency to minimize the carbon footprint, leads to the challenging scientific question of the fatigue resistance of emerging eco-efficient concretes. Since existing knowledge of the traditional Portland-clinker-based binders is largely empirical, it cannot be directly transferred to new binder systems, exhibiting complex chemical and mechanical interactions within the heterogeneous material structure. In contrast to the well-established insight into the high-cycle fatigue of metals, a complete understanding of the fatigue degradation processes in concretes is still lacking. In this research, we are committed to pioneering an innovative approach that establishes a universally applicable link between the chemical/microstructural composition of novel concrete materials and their fatigue resistance. To create an interdisciplinary methodology for the scientific analysis of fatigue-resistant eco-efficient concretes, complementary competences of a multidisciplinary research team will be combined in a concerted application of physico-chemical modeling approaches of hydration processes and advanced methods of multiscale and multifield computational mechanics supported by machine learning and accompanied by a rigorous experimental validation program. The developed coherent methodical framework will include innovative theoretical and numerical as well as tailored experimental approaches covering all relevant spatial and temporal scales to enable realistic predictions of the fatigue behavior of existing and future eco-efficient concrete formulations. This is necessary to give design engineers confidence in the new materials, and to enable design concepts, optimally satisfying requirements for sustainable, economical, and reliable future transportation and energy infrastructure.

Mots-clés : high cycle fatigue,eco efficient concrete,thermodynamics,physical chemistry,multiscale modeling,probabilistic computational mechanics,structural engineering science,material characterization
Projet ERC : REM@KE (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université de Göteborg — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2377758.0 €

The fundamental objective of REM@KE is to reconstruct the sound and the function of lost musical instruments and to develop new theoretical, empirical, and practical tools to explore the embodied musical knowledge emerging from the relationships between these instruments and their performers. Among the great variety of objects of the past that inhabit museums, musical instruments are in a category of their own: if kept silent, music cannot be; if played, their materiality is endangered. These instruments are at risk of being silenced forever, as their conservation becomes the priority. To ensure access for future generations, a radical intervention is needed, to comprehensively study how they sounded and played when they were new, as well as their design principles and construction processes, so that they may be reconstructed, played, and heard both materially and virtually. To investigate the sound of these objects, we have developed a new research framework ‘Cognitive and Digital Organology’ (CaDO) that builds new bridges between organology, performance practice research, and cognitive sciences. CaDO will study the people involved with music, the instruments producing the sounds (interlocked into a system that evolves over time), in a space that is social, material, and digital. Embodied cognitive science will be used to examine how resources from the bodies of builders, players, educators, and listeners determine their musical experiences, fostering new relationships that are formed and transformed in acts of musicking. Thus, CaDO can inspire richer understandings of the experiences of those who engage with historical musical instruments and their replicas. By reinterrogating the relationship between instrument, gesture, and music REM@KE aims to reclaim the sound of historical instruments, improve our understandings of how we engage with them, and guarantee a better future for them.

Mots-clés : organology keyboard organ clavichord harpsichord pianoforte cognition restoration conservation virtual reality mixed reality