Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : UNLEASH (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Centro de Regulación Genómica — Pays : Espagne — Rôle : CO-PI
Acronyme de l'entité : CRG
Type d'entité : Recherche
Financement ERC de l'entité : 2500764.0 €

Alternative splicing (AS) of mRNA precursors plays important roles in tissue-specific gene regulation and biological regulatory mechanisms, as it can radically alter protein expression, cell phenotypes and physiological responses. Altered splicing also contributes to disease mechanisms, ranging from neurodegeneration to cancer. Drugs modulating AS have recently provided the first therapy for Spinal Muscular Atrophy, a common genetic disorder, illustrating the huge potential for treating many other diseases of unmet need, if only we understood the mechanisms controlling splice site selection and how to regulate them with small molecules. Unfortunately, despite decades of research, a comprehensive understanding of the mechanisms that control specificity of AS is lacking. This gap in basic knowledge prevents opportunities to harness splicing modulators as tools to study gene function, novel therapeutics or other biotech applications. This Project addresses head-on the major technical challenges that have limited progress in the AS field. Building on extensive preliminary data, we will use a multidisciplinary approach that combines chemical, structural, cellular, systems biology and machine learning to characterize mechanisms of splice site selection and identify targets for modulating these mechanisms using tool compounds. The outcomes will define key regulatory sequences, splicing factors and molecular interactions involved, thereby illuminating how the splicing machinery efficiently accommodates, yet also discriminates between, a wide range of splice site sequences. This will enable future applications harnessing splice site selection. Our primary goal is to answer the central question, ‘Is it generally possible to modulate splicing with high specificity using small molecules?’ Success will transform our basic understanding of human gene expression and unleash major opportunities for Pharma to develop new therapeutics.

Mots-clés : rna splicing,rna protein interactions
Projet ERC : CombaT7 (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université libre d'Amsterdam — Pays : Pays-Bas — Rôle : CO-PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2954949.0 €

Bacteria interact with their environment via specialised secretion systems that deliver proteins outside of the cell. Due to a bias in research efforts, for many years such systems were assumed to be unique to Gram-negative bacteria. A major exception is the type VII secretion system (T7SS), which is widespread in Gram-positive bacteria and actinobacteria, including the important human pathogen Mycobacterium tuberculosis. The T7SS is a complex secretion apparatus that exports folded proteins and even protein complexes. While secreted substrates are well-known for being crucial players in host-pathogen interactions, our recent data indicate that specific substrates of the relevant opportunistic pathogen Mycobacterium abscessus and the fish pathogen Mycobacterium marinum are also involved in interbacterial antagonism. This makes T7SSs important factors to understand microbial interactions, also for the understudied part of the microbial world. While the mechanism of secretion via T7SSs remains little understood, our preliminary data show that not only their roles but also their substrates are more diverse than thus far thought. Here, we unite leading experts in microbiology, structural biology, cell biology, and biophysics to spearhead research on mycobacterial T7SSs and their roles in both interbacterial and host-pathogen interactions. In this unique consortium, we will (i) define the full trans-envelope T7SS by atomic force microscopy and cryo-electron microscopy, (ii) study the mechanism of transport by creating translocation intermediates, (iii) expand the set of T7SS substrates by extensive proteomics and bioinformatics analysis, and (iv) visualise the role of T7SS in bacterial warfare and host-pathogen interactions using microfluidics, innovative lung-on-a-chip infection models and time-lapse microscopy. This will deliver a deep mechanistic understanding of the diverse roles of mycobacterial T7SSs and provide clues to exploit these systems to combat infections.

Mots-clés : type vii secretion tuberculosis mycobacterium membrane complex toxin host pathogen interactions cryo electron tomography single particle analysis atomic force microscopy microfluidics time lapse microscopy
Projet ERC : OCEAN (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Groupe ENSAE-ENSAI — Pays : France — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 131140.0 €

Until recently, most of the major advances in machine learning and decision making have focused on a centralized paradigm in which data are aggregated at a central location to train models and/or decide on actions. This paradigm faces serious flaws in many real-world cases. In particular, centralized learning risks exposing user privacy, makes inefficient use of communication resources, creates data processing bottlenecks, and may lead to concentration of economic and political power. It thus appears most timely to develop the theory and practice of a new form of machine learning that targets heterogeneous, massively decentralized networks, involving self-interested agents who expect to receive value (or rewards, incentive) for their participation in data exchanges.  OCEAN will develop statistical and algorithmic foundations for systems involving multiple incentive-driven learning and decision-making agents, including uncertainty quantification at the agent's level. OCEAN will study the interaction of learning with market constraints (scarcity, fairness), connecting adaptive microeconomics and market-aware machine learning.  OCEAN builds on a decade of joint advances in stochastic optimization, probabilistic machine learning, statistical inference, Bayesian assessment of uncertainty, computation, game theory, and information science, with PIs having complementary and internationally recognized skills in these domains. OCEAN will shed new light on the value and handling of data in a competitive, potentially antagonistic multi-agent environment, and develop new theories and methods to address these pressing challenges. OCEAN requires a fundamental departure from standard approaches and leads to major scientific interdisciplinary endeavors that will transform statistical learning in the long term while opening up exciting and novel areas of research.

Mots-clés : machine learning,federated learning,computational game theory,multi armed bandits,bayesian inference,markov chain monte carlo,multi agent reinforcement learning,online matching markets,data market,incentive
Projet ERC : UnMySt (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université de Strasbourg — Pays : France — Rôle : Partner
Acronyme de l'entité : UNISTRA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1102500.0 €

Polaritonic Chemistry is a new and exciting field that has emerged from the fusion of chemistry and cavity quantum electrodynamics. In this innovative realm, and specifically under Vibrational Strong Coupling (VSC), hybridizing molecular vibrations with electromagnetic cavity modes has been shown to modify the rate and yield of reactions, solvent polarity and other molecular properties, in the absence of any illumination. The prospects for VSC as a versatile tool for chemistry and materials science have sparked a worldwide surge of interest, leading to substantial advances in recent years. Nevertheless, deciphering the underlying mechanisms by which VSC affects material properties still poses formidable challenges, impeding the utilization of VSC to its full potential. The goal of UnMySt is to construct a complete framework for cavity-controlled chemistry, built upon a comprehensive mechanistic understanding of VSC on both the molecular and supramolecular levels. As leading scientists in the field, we will pursue this goal by joining our forces in seeking answers to these pivotal questions: 1. What is the mechanism that links the local character of molecular reactivity with the collective nature of VSC? 2. Do the thermal equilibrium properties of materials change under VSC and how are such modifications expressed in polaritonic chemistry? 3. What are the manifestations of VSC on non-equilibrium dynamics such as solvent reorganization or charge transfer? 4. Can symmetry considerations provide intuitive guidelines for cavity-controlled chemistry? Can symmetries imposed or broken by the cavity be used to tailor its impact on reactivity? Our synergistic experimental and theoretical efforts will reveal novel physical mechanisms and will lay the qualitative and quantitative foundations for the rational design of strongly coupled molecular systems. The results of UnMyST will unleash the potential of polaritonic chemistry as a new tool for synthesis and materials science.

Mots-clés : cavity polaritons,polaritonic chemistry,vibrational strong coupling,spectroscopy,electronic structure,molecular dynamics,electronic structure methods,quantum electrodynamics density functional theory
Projet ERC : i2B (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Université de Bergen — Pays : Norvège — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 26250.0 €

The Arctic Ocean is turning blue. Abrupt Arctic warming and amplification is driving rapid sea ice decline and irreversible deglaciation of Greenland. The already emerging, substantial consequences for the planet and society are intensifying and yet, model-based projections lack validatory consensus. To date, we cannot anticipate how a blue Arctic responds to and will amplify an increasingly warmer future climate, nor how it will impact the wider planet and society. Climate projections are inconclusive as we critically lack key Arctic geological archives that preserve the answers. This “Arctic Challenge” of global significance can only be addressed by investigating processes, consequences, and impact of past “greenhouse” (warmer than present) states. The timeliness of i2B is tied into retrieval of revolutionary, new Arctic geological archives of past warmth and key breakthroughs in climate model performance that will be integrated in a concerted framework beyond state-of-the-art. i2B will deliver a ground-breaking, synergistic framework to answer the central question: “Why and what were the global ramifications of a “blue” (ice-free) Arctic during past warmer-than-present-climates?” This will be addressed through three connected, cross-disciplinary objectives integrating the expertise, knowledge, and skill-sets of three PIs and their different Arctic paleo-climate and modelling teams. i2B will quantify cryosphere (sea ice, land ice) change in a warmer world (O1) that will form the scientific basis for understanding the dynamics of Arctic cryosphere and ocean changes (O2), to enable quantitative assessment of the impact of Arctic change on ocean biosphere, climate extremes and society (O3) that will underpin future cryosphere-inclusive IPCC assessments. i2B will solve the “Arctic Challenge” with the synergistic multiplier of the 3 PIs` expert capabilities providing pioneering knowledge on how a blue Arctic impacts Earth’s climate during greenhouse climate states

Mots-clés : arctic ocean,greenhouse climate
Projet ERC : CODICUM (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université de Bergen — Pays : Norvège — Rôle : CO-PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2422614.0 €

Medieval books were instrumental in shaping European history, communicating rituals, stories and ideas as they were read, copied and shared. To modern scholars they illuminate trade, craft, religious, social and intellectual networks. Less than 10% of the European corpus survives, and in Scandinavia the situation is far worse. However, by historical accident a very high number of Latin fragments – c. 50.000 – from these precious books have been preserved. CODICUM will study and analyse the Nordic book fragments as sources to medieval book culture and its networks. While parchment fragments are found throughout Europe, the numbers and the randomness of their survival in the Nordic countries lend them a special significance. The time is now ripe for interrogating this promising material as one unique European archive by combining approaches from the humanities and the sciences. How was Scandinavia included in different intellectual networks and how did these networks evolve and overlap? How was book production adapted to the limited resources of the north? What can this cross-national archive teach us about curating textual heritage in the long term? CODICUM is led by PIs from four different fields – palaeography, literature, history, and bio-codicology. This unique blending of research expertise enables an innovative synergy which will expand the perspective of European book history c. 1000-1500, reconnect fragments to each other and digitally ‘reassemble’ medieval books, explore the craftsmanship associated with book production, reveal the relationships between the transmitted manuscripts material and illuminate the international networks linking Northern Europe. Researching medieval book culture on an unprecedented scale, CODICUM will seek to resituate our understanding of the book in shaping the Nordic region and connecting the region to the rest of Europe thereby pushing the poorly known Nordic fragment archive into the fore of European book-historical research.

Mots-clés : parchment,bio codicology,ecclesiastical history,monastic history,crafts,scandinavia
Projet ERC : DEMI (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Université de Berne — Pays : Suisse — Rôle : PI
Acronyme de l'entité : Unibe
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2498125.0 €

It is our aim to transform the research field of electrocatalysis from the established “initial (as-synthesized) state approach” to a data-centric understanding of the metastable active interface of electrocatalysts, constantly evolving under reaction conditions. We want to overcome the limitations of elemental or binary alloy catalysts by exploring and exploiting high entropy materials (HEM) as a discovery platform for sustainable materials, with the aim to identify in the extremely large, multidimensional search space new electrocatalysts that are both stable and active. To understand and control the active interface of HEM electrocatalysts, we combine the core expertises of the PIs: theoretical modelling and simulations, high-throughput synthesis and characterization, nanoparticle synthesis, electrochemical operando techniques as well as machine learning. Our synergistic approach will significantly advance these individual competences by key conceptual innovations: (i) Evolutionary screening of micro-libraries to efficiently identify stable materials covering the complete HEM composition space; (ii) Accelerated atomic-scale characterization of HEM surfaces by combining combinatorial HEM synthesis with atom probe tomography; (iii) High-throughput operando experiments with thin film material libraries; (iv) Developing inverse activity-structure relationships and theoretical descriptors for metastability; v) Implementing active learning approaches based on materials informatics and using a semantic data lake. We will establish a theory of metastability as a core concept for the understanding of electrocatalysis for the most important energy conversion reactions: oxygen reduction and evolution, and CO2 reduction. Instead of passively accepting the degradation of catalysts during operation, we will direct the evolution through the highly multidimensional space towards long-lasting, active HEM interfaces.

Mots-clés : electrocatalysis,high entropy alloy catalysis,materials discovery,stability degradation
Projet ERC : MitoContact (Horizon Europe, appel 2025, Synergy grants)
Entité participante : Université de Berne — Pays : Suisse — Rôle : PI
Acronyme de l'entité : Unibe
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3669331.0 €

Mitochondria are central to modern eukaryotic life, but how they carry out their functions in space and time within the cellular milieu is remarkably enigmatic. Contributing to the complexity of this question, mitochondria face dual existential challenges: supporting their life cycle as self-reproducing, DNA-containing organelles; and supporting the energetic and signaling needs of the host cell. A universal feature in how mitochondria address these challenges is via engagement in membrane contact sites (MCS) - sites of intracellular signaling or biomolecular exchange - with partner organelles. Candidate MCS proteins between partners range into the hundreds, driving speculation that diverse contacts exist. However, technological limitations in measuring the composition, structure, dynamics and physiology of transient MCS have hindered progress in dissecting their functional diversity.  Our project will develop and apply cutting-edge technologies to investigate the dynamics and molecular organization of MCS, to reveal how individual contacts locally coordinate mitochondrial physiology and function. We will deploy (1) chemical biology “recorders,” enabling us to trace the history of MCS and physiology. We will combine this with (2) live-cell “smart microscopy,” driven by closed-loop feedback through real time neural-network recognition of cellular events, to capture dynamics with high specificity and spatio-temporal resolution and (3) cellular cryo-correlative microscopy to obtain structural snapshots and gain insights into MCS molecular architecture. We will focus on heterotypic and homotypic contacts implicated in mitochondrial proliferation, degradation, molecular exchange, and metabolic states. Our synergistic approach will allow us to screen for MCS inhibitors or stabilizers and measure the impact of disrupting contacts. Thus, we expect our project to have broader implications for therapeutics, and our tools to impact fundamental biological discovery beyond MCS.

Mots-clés : mitochondria,membrane contact sites,fluorescence microscopy,electron microscopy,cryo em,smart microscopy,super resolution microscopy,fluorescent biosensors
Projet ERC : CultCryo (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Université nationale australienne — Pays : Australie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2216181.25 €

Artificial cooling fundamentally shapes the world in which we live. Since the onset of the Cold War, cooling and freezing technologies have become increasingly vital for a wide array of everyday practices, from nutrition, health and reproduction to dwelling, telecommunication, scientific research and economic productivity. A global system of cold storages, cold chains and air-conditioned spaces has become an energy-intensive yet barely considered planetary infrastructure: an “artificial cryosphere”. Artificial cold has drastically restructured life both on a biological and social level, yet the far-reaching impact of this technology is still largely unexplored and unresearched. Recent studies estimate that global cooling demand will increase five-fold by 2050, dramatically exceeding our future energy budget and urgently calling for change. CultCryo argues that avoiding the impending global cooling crisis will be impossible if we do not understand how the planetary infrastructure of artificial cold is deeply interwoven in cultural practices. Thus, in order to analyze the constitution of “cryogenic cultures”, we will undertake four interdisciplinary multi-sited case studies in the domains of food supply, air conditioning, biomedicine and computing. We develop innovative approaches using mixed-methods rooted in the history of technology, geography, digital history of concepts, ethnography and the philosophy and ethics of technology. Breaking ground for an innovative interdisciplinary field of research, CultCryo will provide the first geographical mapping of the cryosphere, a historical reconstruction of its emergence, an ethnographic account on its cultural constitution, and a philosophical analysis and ethical assessment of its underlying norms and values. Thereby, we develop a corpus of urgently needed knowledge to critically analyze a pressing global phenomenon while also identifying alternatives towards a more sustainable future of artificial cold.

Mots-clés : ethnography,technology assessment,language technology,digital history of concepts,cultural analysis,value analysis and theory,cryopreservation,cooling,infrastructures,public health,sustainability,
Projet ERC : MUTAHOME (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Queen Mary University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : QMUL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3129582.5 €

Healthy tissues become progressively populated of clonally expanded cells that have acquired somatic mutations. Often these mutations modify cancer genes promoting cell plasticity, self-renewal, and growth, all features known to decline with ageing. Despite being pervasive across tissues and persistent throughout life, only rarely mutant cells become pathogenic. Here we hypothesise that somatic mutations enhance tissue integrity by increasing the fitness of stem/progenitor cells (SPCs) to counterbalance their age-induced decline. Increased SPC fitness at the cellular level increases the fitness at the tissue level, thus preserving the overall tissue regenerative potential. To test this hypothesis, we propose to investigate the effect of somatic mutations on SPC fitness in solid tissues and blood using complementary and synergistic approaches specific to our teams, bridging the historically distinct fields of evolutionary genetics and stem cell biology. Through the analysis of human tissues and the use of complex mouse models, we will dissect the interactions between mutant SPCs and their niche, at homeostasis and upon insults. We will determine whether the expansion of mutant SPCs over time leads to a progressive decline in SPC diversity, which eventually increases disease risk. We will adopt a progressive approach. We will first characterise the mutant clone (WP1) and its crosstalk with the niche (WP2) at homeostasis. We will then test the response of mutant clone and niche to physiological (WP3) and pathological (WP4) challenges. We will finally assess the occurrence of a multiorgan crosstalk conveyed by mutant blood on mutant solid tissues (WP5). This study will radically transform our understanding of tissue homeostasis and clarify the relationship between somatic mutations, ageing and disease. A deeper knowledge of the mechanisms that maintain the homeostatic equilibrium over time is the first step to guide intervention and disease prevention.

Mots-clés : somatic mutations,tissue stem cells,homeostasis