Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : SKIN2DTRONICS (Horizon Europe, appel 2024, Synergy grants)
Entité participante : École polytechnique fédérale de Lausanne — Pays : Suisse — Rôle : PI
Acronyme de l'entité : EPFL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2632444.0 €

The goal of SKIN2DTRONICS is to demonstrate the large scale integration (LSI, transistor count larger than 1000) of soft and thin (skin-like) electronic devices on ultra-flexible substrates, capable of conformally adapting to any rough and curved surface. This vision will be realized by atomically thin two-dimensional materials (2DMs) that possess compelling properties for this application: high electronic performance, environmental stability, low toxicity and cytoxicity, and extreme resilience to mechanical deformations. With the increasing pressure towards ubiquitous electronics (wearables, Internet-of-Things, smart patches, etc.) it is urgent to develop electronics that can be easily integrated on the surface of everyday objects and, in the case of health monitoring applications, on a variety of rough biological surfaces. Today’s conformal electronics is mainly based on conformal sensors with flexible and stretchable electrodes interfaced to bulky silicon chips, responsible for processing. This approach is prone to mechanical failures, especially at the solderings, as the connection between the conformal and solid components remains very challenging. The research will rely on the complementary conjuncture of four fields: sensors, 2D-based electronics, flexible electronics and biomedical engineering that the PIs of the consortium bring, each of them recognized experts in their respective fields and with a valuable experience in leading ERC projects.

Mots-clés : conformable electronics,wearable systems,on skin electronics,ultra flexible circuits,two dimensional materials
Projet ERC : CombaT7 (Horizon Europe, appel 2024, Synergy grants)
Entité participante : École polytechnique fédérale de Lausanne — Pays : Suisse — Rôle : PI
Acronyme de l'entité : EPFL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2253904.0 €

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 : Resilience (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Université de la Colombie-Britannique — Pays : Canada — Rôle : PI
Acronyme de l'entité : UBC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1952122.5 €

There is an urgent need to understand the catastrophic effects that global environmental and climate change can have on the Earth, its system components and ecosystems. One area of critical concern is the imminent high-impact, abrupt and irreversible tipping of ecosystems. Recent discoveries indicate that tipping could be evaded and even reversed in ecosystems through spatial pattern formation of vegetation, thereby creating pathways of resilience. Many undiscovered pathways of resilience through spatial pattern formation could exist for tipping-prone ecosystems. This resilience could be even enhanced by the unexplored connection between spatial pattern formation and community assembly. The aim of RESILIENCE is to fundamentally advance our understanding and predictions of tipping and critical transitions in ecosystems and reveal how these can be evaded and even reversed through spatial pattern formation. The RESILIENCE team consists of field-leading and complementary PI’s and is capable of addressing all aspects of this overarching project, linking theory and observation, spanning the fields of ecology, physics and mathematics. RESILIENCE will develop a new theory for emerging resilience through spatial pattern formation and link this with real tipping-prone biomes undergoing accelerating global change: savanna and tundra. Central to our theoretical approach is the novel mathematical connection between the origin of the formation of patterns and their resilience once they emerged. Our empirical approach will include the analysis of existing and new data from in situ observations and drone and satellite-based remote sensing. Our research will reveal which conditions and spatial patterns lead to the evasion and even reversal of tipping. Identifying these conditions and patterns will also expose how human interventions can prevent or reverse tipping and uncover that tipping-prone ecosystems could be much more resilient than currently thought.

Mots-clés : self organisation,spatial pattern formation,tipping points,critical transitions
Projet ERC : TREATLIVMETS (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Université Vie-Santé Saint-Raphaël — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2317453.75 €

Liver metastases commonly develop in up to 50% of patients with various cancer types. The most common cancer that metastasizes to the liver is colorectal cancer (CRC). At least 25% of CRC patients develop colorectal liver metastases (CRLM) during their illness. CRLM represent the major unmet clinical need for this malignancy, as the 5-year survival rate of patients with unresectable disease does not exceed 2%. New therapies that promote antitumor immunity have been recently developed, mostly focusing on enhancing T cell responses. Although these therapies have led to unprecedented successes, only a minority of patients benefit from these treatments, highlighting the need to identify new cells and molecules that could be exploited in next generation immunotherapies. Given the crucial role of innate immune responses in immunity, targeting these responses opens up new possibilities for tumour control. We hypothesize that the immunotherapy of liver metastases can be significantly improved through harnessing the biology of innate lymphoid cells (ILC), such as Natural Killer (NK) cells and ILC1s, and myeloid cells such as macrophages and DCs. Our team brings together experts in the biology of tissue-resident myeloid (Ginhoux, PI4) and lymphoid (Gasteiger, cPI) cells, in liver immunology (Fumagalli, PI3), and in the development of novel immunotherapeutic strategies that modulate immune cells in the fight against cancer (Vivier, PI2). By combining cutting-edge single cell and spatial transcriptomics of human patient samples with cross-species analyses in advanced genetic mouse models, we aim (1) to identify cellular interactions defining the metastatic tumor microenvironment across murine and human tissue-specimens, (2) to investigate immune cell functions regulating metastatic disease using a unique combination of advanced genetic mouse and human tissue models, and (3) to harness the anti-tumoral functions of innate immune cells via next generation cell engagers.

Mots-clés : liver immunology,liver metastasis
Projet ERC : HepaModulatoR (Horizon Europe, appel 2025, Synergy grants)
Entité participante : Université Eberhard Karl de Tübingen — Pays : Allemagne — Rôle : CO-PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 7470484.25 €

RNA base editing, catalyzed by ADAR enzymes, is a natural process that diversifies protein function by modifying mRNA. Redirecting ADAR activity with RNA-based drugs holds significant promise for correcting genetic mutations and uniquely enables precise modulation of protein function. However, major challenges remain to fully unlock this potential. In this collaborative effort, we present a target discovery platform and demonstrate in vivo proof-of-concept (PoC) that targeted RNA base editing can mitigate chronic liver disease. Our team combines its groundbreaking insights and tools to predict functional editing computationally (PI Levanon), efficiently screen for effective edits (PI Stafforst), and establish functional PoC in animal models of liver disease (PI Heikenwälder). Chronic liver disease stems from disturbances in the liver microenvironment caused by chronic viral infections, alcohol intake, sedentary life-style/high-calorie diets or autoimmunity, all disrupt hepatocyte metabolism and regulatory signalling. This ultimately leads to liver inflammation, fibrosis, and liver cancer. We suggest that targeted RNA base editing is well-suited to counteract liver disease by modulating protein function and upregulating hepatoprotective proteins. To maximize the likelihood of success, our team addresses three Focus Areas, each representing a distinct stage of liver disease: In Focus Area 1, we aim to modulate liver metabolism (promoting catabolism) at an early disease stage. In Focus Area 2, we seek to reduce chronic inflammatory signalling at the mid-stage. Finally, Focus Area 3 focuses on generating highly immunogenic neoantigens in cancerous liver tissue to stimulate immune therapies at advanced stages. Overall, this project will push far beyond the current state-of-the-art in this field, significantly advancing this innovative therapeutic modality. We aim to make a substantial impact on Europe’s society, healthcare systems, and pharmaceutical industry.

Mots-clés : adar,rna editing,rna drugs,base editing,chronic liver inflammation,mouse models liver disease,spatial metabolomics,masld,mash,liver cancer,neoantigen,rna editing prediction,rna structure prediction,computational biology,genomics transcriptomics,large language models,machine learning
Projet ERC : KARST (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Université Simon Fraser — Pays : Canada — Rôle : Partner
Acronyme de l'entité : SFU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 268250.0 €

Karst aquifers are a treasure and a threat: while up to 25% of the world population depends on them for drinking water, they also have capabilities for extremely fast conduction of water and contaminants. In the light of climate change, we need to prepare for extreme flooding and understand the consequences for karst aquifers. Despite their socio-economic importance, decades of research, and high-profile disasters, karst structures and processes remain notoriously difficult to assess. Because of the complexity of karst and its lack of accessibility, the foundations of flow and transport modeling in karst systems are weak. Key phenomena related to extreme events such as flash floods and heavy tails in tracer recovery are still beyond current modeling capabilities. KARST will establish the next generation of coupled stochastic modeling frameworks to predict karst processes, assess the vulnerability of karst aquifers, and forecast their response to extreme events. Our approach will bridge structures and processes on all scales, far beyond the capabilities of current theories and computer simulations. This will be achieved by targeting three key objec- tives: (i) Identification and quantification of flow and transport dynamics at the conduit scale. (ii) Characterization and modeling of karst network structure at the catchment scale. (iii) Derivation of a new upscaled approach to predict karst processes at different resolution scales. Together, this will result in an unprecedented multiscale modeling framework for the prediction of flow and transport in karst. Solving this long-standing problem is possible thanks to the synergy of the KARST PI team combining the set of skills and knowledge (hydrogeology, physics, mathematics) required to make a ground-breaking step in this field. Beyond that, the new approach is expected to impact other real-world systems in medicine (capillary networks), neuroscience (brain microcirculation) or glaciology (meltwater flow in glaciers).

Mots-clés : karst,networks,upscaling,flow,transport,graphs,structure,anomalous transport,continuous time random walks,lagrangian analysis,particle methods,dispersion,turbulent transport,groundwater,contamination,floods
Projet ERC : CONCERT (Horizon Europe, appel 2025, Synergy grants)
Entité participante : Conseil national de la recherche — Pays : Italie — Rôle : PI
Acronyme de l'entité : CNR
Type d'entité : Recherche
Financement ERC de l'entité : 2717500.0 €

Conical intersections (CIs) are regions in the potential energy surface of molecules where different electronic energy levels intersect, leading to the breakdown of the Born-Oppenheimer approximation and promoting non-adiabatic transitions between electronic states. CIs preside over essential ultrafast processes in photobiology, photochemistry, and materials science as they can be viewed as “doorways” through which a photoexcited vibrational wave packet (WP) is efficiently funnelled to a lower-energy electronic state. Despite theoretical predictions, CIs have been experimentally elusive so far, due to the extreme speed of the processes leading to and occurring at the CIs and to the associated large variation in the energetic landscape of the molecule, calling for extreme spectral and temporal resolutions. Leveraging recent experimental advances in the generation of ultrashort soft X-ray pulses and conceptual advances in nonlinear optical spectroscopy, CONCERT aims to: i) directly visualise the very moment in which the molecular WP passes through the CI and the associated quantum mechanical electronic coherences; ii) use this knowledge to control, using tailored light pulses, the WP dynamics in the vicinity of a CI and, ultimately, the outcome and the yield of a photochemical reaction by operating exactly where the fate of the process is decided. CONCERT will have both fundamental and applied impact. On the one hand, it will enable the understanding of the molecular mechanisms driving the passage of a WP through a CI, advancing our knowledge of nature and providing design guidelines for artificial molecular systems that mimic the natural ones. On the other hand, it will offer the ability to control the rates and branching ratios of photochemical processes by manipulating the excited state WP in the critical region that determines its ultimate path, fulfilling the long-held dream of using light as a photonic catalyst to control the outcome of chemical reactions.

Mots-clés : ultrafast spectroscopy conical intersections quantum dynamics
Projet ERC : PEPS (Horizon Europe, appel 2022, Synergy grants)
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 : 3132850.0 €

Neural stem cell (NSC) populations in the vertebrate brain generate adult-born neurons for plasticity, growth, and repair. Neurogenic and gliogenic capacity, based on long-term NSC maintenance, functionally define “stemness”. Stemness embodies massive NSC heterogeneity at the single cell level and requires control of maintenance or differentiation decisions at the population level. These features remain mechanistically unreconciled. We hypothesise that spatiotemporal interactions among heterogeneous NSCs are coordinated to control the population behaviour. Thus, we propose a multi-dimensional project exploring these features in time and space, to decode the mechanistic principles of stemness. To this end, we bring together experimental and theoretical groups with complementary expertise in NSC biology, biostatistics and mathematical modelling. In an iterative experimental-mathematical approach, we will (1) solve the topology of individual NSC trajectories in transcriptomic space, (2) identify local cell-cell coordination mechanisms that impact these trajectories in situ, and (3) decode the resulting systemic properties and outputs of NSC ensembles at long-term and large spatial scales. This programme will result in original methods, including retrospective transcriptomics in single cells, innovative barcode transfers, and a novel mathematical framework to describe structured spatio-temporal population dynamics. We will focus on two biological model systems, the adult mouse ventricular sub-ventricular zone and zebrafish pallium, where NSC ensembles display comparable heterogeneity but differ in spatial organisation and fate dynamics. Together, PEPS will uncover the general principles and regulatory mechanisms of perpetuating stemness in time and space. It will lay the conceptual and methodological foundation to manipulate stem cell systems to improve their stability or output, and also produce new methods of universal value for studying cellular systems.

Mots-clés : adult neural stem cells,zebrafish pallium,ventricular subventricular zone,spatio temporal population dynamics,single cell multi omics,barcoded transfer connectome,brain injury,single cell perturbations,mathematical modelling,structured population models,partial differential equation,high dimensional statistics,dimension reduction
Projet ERC : UnLost (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université de Naples - Frédéric-II — Pays : Italie — Rôle : CO-PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3661178.75 €

The loss of something precious triggers an immediate instinct to find it. But what if the quest does not end there? We see it and find it, yet the precious object is irreparably damaged, and its true knowledge is locked away behind its damage, frustratingly denying us access to the information it holds. In such cases, the object essentially remains lost. Each day, in fact, treasured relics bearing unique witness to the human experience are lost to decay and damage due to the elements of the environment, the ravages of time, and the hands of war. And while we rejoice at every inspiring, arduous discovery and recovery of a physical object, we often must acknowledge that much of the knowledge it contains remains lost. UnLost will revolutionise the way we study damaged, complex heritage materials by capitalising upon today’s vast scientific capabilities. UnLost will harness these capabilities to capture immense amounts of disparate data and combine them with a novel, much-needed systematic and rigorous process to extract, integrate, study, archive, and protect multi-modal data so that lost knowledge is rendered – and kept – UnLost. The Herculaneum papyrus scrolls, buried and carbonised by the eruption of Mt. Vesuvius in 79 CE and then excavated in the 18th century, represent the epitome of such found, yet still lost, heritage. The only complete Classical library from the ancient world to have survived and been found in situ, much of the textual material contained in this renowned collection remains hidden within its profoundly damaged and fragmented form. The goal of the UnLost team is to create and deploy new methods of digitization, AI-inspired inference, and archival-quality complex digital objects so as to revive what has been lost from Herculaneum and develop new benchmark approaches for the restoration of damaged heritage objects as a whole.

Mots-clés : digital restoration,herculaneum papyri,material analysis,physical conservation,born digital editions,virtual unwrapping,ancient scrolls,hidden papyrus layers,structured data and metadata
Projet ERC : UNFOLD (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Conseil supérieur de la recherche scientifique — Pays : Espagne — Rôle : CO-PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 2741588.75 €

Mammals with large brains and higher cognitive functions have a richly folded cerebral cortex. Folding abnormalities are linked to various cognitive disabilities. Despite its relevance in clinical diagnostics, the causes and consequences of cortex folding remain poorly understood. While cortex folding was long assumed to result from a limited skull volume, it is a developmental process intrinsic to the cortex. We hypothesize that cortex folding emerges from a dynamic interplay between mechanical and molecular processes, and that far from being an epiphenomenon, it has major consequences for brain architecture and function. UNFOLD will test this hypothesis by integrating genomics, cell biology, mechanics of brain development and computational modeling. Our interdisciplinary team will apply in vitro, in vivo and in silico approaches to brain tissue of strategically selected animal models. First, we will map molecular, cellular, and mechanical events accompanying cortex folding. Next, we will investigate the effects of genetic perturbations of cell biological processes on tissue mechanics, and vice versa, to identify key mechanisms leading to cortex folding and elucidate their dynamic interactions. Then, we will test the universality of these mechanisms by inducing folds in species with a smooth brain. Finally, we will decipher the consequences of cortex folding on neural circuit function and animal behavior. Our project integrates current, opposing concepts of cortex folding by adopting an interdisciplinary and multiscale perspective. Unraveling the dynamic interactions between molecular, cellular, and mechanical events during development will provide unprecedented insights into the determinants of cortical anatomy and brain organization. Our work, bridging physical and life sciences, will lead to new insights into normal and pathological brain development, paving the way to a new research area of integrated neurobiology with potential applications in modern medicine.

Mots-clés : cerebral cortex folding ferret mouse neurogenesis neuron migration viscoelasticity radial glia cell xenopus development mechanics afm tissue mechanics