Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MakingBlood (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Fundación Josep Carreras Contra la Leucemia — Pays : Espagne — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 737750.0 €

Life-saving blood cell replacement depends on voluntary donors. Availability is a challenge for specific groups, and 25% of patients needing blood stem cell transplants lack a compatible donor. The ideal alternative is clinical-scale production of Haematopoietic Stem Cells (HSC) from laboratory-maintained tissue-compatible sources, to provide an off-the-shelf source of blood cells. HSC are generated in the aorta/gonad/mesonephros region of the embryo, expand in the foetal liver, and are maintained in the bone marrow of adults. Current attempts to generate HSC in vitro do not consider the changing cellular, chemical, and physical characteristics of the different environments met by HSC in vivo from embryo to adult, and have been unable to reliably produce functional HSC. MakingBlood aims to establish a proof-of-concept platform for robust generation of human HSC from pluripotent stem cells by developing a self-organising gastruloid model of embryonic HSC generation without genetic manipulation, and successively recapitulating the natural foetal and adult HSC development environments. MakingBlood brings together an expert in HSC embryonic development, a national blood bank research director with expertise in adult HSC, an expert in molecular regulation of cell fate choices, and a bioengineer with expertise in mechanical and chemical integration for tissue production to deliver this breakthrough platform. By using state-of-the-art technology and multidisciplinary approaches, we will systematically detangle cellular, chemical, and physical properties of natural HSC generation, amplification and maintenance microenvironments, and iteratively identify essential elements that enable and promote HSC function. We will integrate key elements into modular scalable engineered niches to establish a HSC production platform, which can be developed as a bioreactor for on-demand blood production, and eventually replace donations as the clinical source of HSC and mature blood cells.

Mots-clés : gastruloids,engineered stem cell niches,mechanobiology,hematopoietic stem cells,developmental hematopoiesis
Projet ERC : SHAPINCELLFATE (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Sorbonne Université — Pays : France — Rôle : Partner
Acronyme de l'entité : Sorbonne U
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 50000.0 €

Cells are often depicted as irregular spherical objects - the shape they adopt in suspension. However, the packed environment of tissues alters this simple shape, causing large cell deformations. This occurs during normal tissue growth and is even more pronounced upon tissue overgrowth, as in the case of solid tumors. Cell shape changes frequently occur in migratory cells, such as immune cells that patrol the organism within interstitial tissues, and cancer metastases that escape from the primary tumor to invade healthy tissues. In all cases, cells adapt and survive even to very large deformations. The mechanisms underlying such response and the long-term consequences that repeated cell shape changes have on physiology and pathology remain largely unknown. We have observed that changes in the shape of cells and organelle(s) induce reversible and irreversible modifications in their behaviour and function(s). We hypothesize that cells use such mechanisms to integrate the successive deformations of distinct amplitudes and durations that they experience during their lifetime. This implies the existence of “shape-induced memory effects” that not only encode the geometrical and mechanical history of the cell but also dictate its fate. Here, we propose to tackle the molecular mechanisms and physical principles accounting for shape-induced memory effects and to evaluate their impact on immunity and cancer. We will focus on two cell types that undergo large shape changes in vivo, and communicate to establish cancer immunity: (1) dendritic cells, which initiate adaptive immune responses, and (2) cancer cells derived from mammary epithelia. Our project will reveal whether boundary conditions imposed by physical confinement are overarching determinants of cellular behaviours at different spatial and temporal scales, and may further establish novel clinical paths for a holistic understanding of early malignancies and their recognition by the immune system.

Mots-clés : cell shape,cell deformation,organelle deformation,signaling pathways,dendritic cells,cancer cells,physical modeling
Projet ERC : Synergy-Plague (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 2703000.0 €

Synergy-Plague is a multi-disciplinary project to bring our knowledge and understanding of plague, past and present, to new heights. Focussing on the environmental, biological, and societal aspects of plague outbreaks in Eurasia between circa 1300 and 1900 CE, it will address four main questions: (1) Why/how did plague re-emerge in 14th century Central Asia? (2) Why/how did plague re-occur and spread in Eurasia after the Black Death? (3) Why/how did clinical and demographic patterns of plague infection differ across space and time? (4) Why/how did plague disappear from Europe and the Middle East in the 18th and 19th centuries? Our project is based on the hypothesis that plague waves and clinical differences resulted from unique alignments of multiple events: environmental (climatic and soil-chemical), biological (from individual to ecosystem) and societal (demographic, socio-economic and political). Four PIs from the natural sciences and humanities, together with their team members, will jointly study how plague re-emerged in 14th century Central Asia and radiated repeatedly from Eurasian wildlife reservoirs in the following centuries, only to disappear in the 18th-19th centuries. We will develop and analyse new dendrochronological and (paleo-)soil data, textual documentary evidence, and epidemiological models. To understand how plague reached and spread in human populations, paleo-environmental and historical data together with relevant experimental work will be combined with statistical and mathematical modelling. To appreciate why clinical signs and mortality rates varied in space and time, historical evidence will be examined together with new entomological data and ancient DNA (aDNA) of historical plague strains (from humans and anthropophilic rodents). Synergy-Plague will revolutionise our understanding of plague and contribute to our ongoing struggle with epidemic diseases, present and future.

Mots-clés : black death,plague pandemics,rodent burrow systems,human and rodent ectoparasites,plague reservoirs,soil properties,past cimate,epidemiology,statistical and mathematical modeling,experimental work
Projet ERC : AI4AMR (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Institut Pasteur — Pays : France — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 4158723.0 €

Antimicrobial resistance (AMR) is one of the most pressing global health problems of our times. To counteract AMR, we urgently need new antibiotics, particularly with novel modes of action (MoA). However, while typical antibiotic screening pipelines can identify compounds that impair bacterial growth, they are unable to predict drug targets and MoA so must be followed up by time-consuming target identification steps. By synergizing our expertise in microbiology, genetics, advanced microscopy, metabolomics, medicinal chemistry, computational biology and artificial intelligence (AI), we propose to create a new pipeline at the forefront of the antibiotic discovery field that will be capable of informing simultaneously on the bioactivity and MoA of new antibiotic candidates. Working with seven pathogens, our improved acquisition strategies for both imaging-based high-content screening and metabolomics will generate a massive dataset of rich multidimensional phenotypes of libraries of genetic mutants and of bacteria exposed to a range of perturbants, at unprecedented scale. Deep learning analyses will then enable us to explore these massive datasets to correlate chemical-induced phenotypes to those from mutants, linking drugs to genes to elucidate the target/MoA of new drugs. This innovative pipeline will enable us to explore unique chemical spaces, including complex natural product extracts (without the need for isolation of individual components) and novel synthetic compounds. Promising candidates with novel MoA will be tested against drug-resistant clinical isolates and against a future pandemic 'pathogen X', demonstrating our pipeline as an AI-powered solution for achieving higher productivity in antibiotic discovery. AI4AMR will provide the community with a new pipeline to efficiently screen large compound libraries to identify novel antibiotics and define their MoA and target, helping directly to combat AMR.

Mots-clés : antibiotics,metabolomics,chemical libraries,natural products,mutant libraries,high content imaging,artificial intelligence,drug discovery
Projet ERC : Bright Chips (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université technique de Munich — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 4572382.5 €

Our vision is to revolutionize information and quantum technologies by blending photonic and electronic functionality onto a single chip. This long-standing challenge has remained unattainable because chips, fabricated by mainstream silicon technology, cannot emit light. Computer chips would be much faster and consume far less energy if they would operate with light. In addition, optical functionality will be transformative for quantum computation since silicon technologies are by far the most scalable allowing the connection of millions of quantum bits using light. We envision to realize light-emitting chips by changing the most fundamental property of a given material – the way in which the atoms are arranged in space. Hereby, we explore a novel material, hexagonal SiGe, with an atomic arrangement that differs from the natural cubic material, rendering it optically active. We will understand light emission mechanisms in the classical and quantum regimes, when many, few and even single photons are generated on demand. Moreover, we will elucidate the optical and electrical properties of quantum structures, aiming for landmark experiments, each of which can open a new research field: i) a SiGe-based laser, which demonstrates the photonic potential of the material, and is a device directly relevant for optical communication on a chip, ii) a SiGe quantum light source, which uniquely combines the stability of the quantum state with optical functionality and iii) spin quantum bits that can be rapidly manipulated, upscaled and are long-lived due to the expected material properties.  In the ultimate experiments, we connect the advantageous opto-electronic properties of this new material system and investigate i) active photonic circuits in which light is switched by light, and ii) the transduction of a static electronic quantum state (spin) into a propagating photonic state to connect distant qubits.

Mots-clés : crystal growth,nanolaser,quantum photonics,silicon quantum electronics,spin qubit
Projet ERC : CONCERT (Horizon Europe, appel 2025, Synergy grants)
Entité participante : University of California System — Pays : Etats-Unis — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1700000.0 €

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 : Cat4CanCenter (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Université d'Amsterdam — Pays : Pays-Bas — Rôle : CO-PI
Acronyme de l'entité : UvA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3453377.5 €

The increased incidence and mortality of tumors that do not respond to standard of care or other targeted therapies is a major challenge in clinical management of these cancer patients. In order to provide innovative therapeutic avenues for treatment refractory patients, it is urgent to develop novel mechanisms of anticancer drugs mode of action that will overcome the drawbacks of current therapies. In Cat4CanCenter, we will merge the research fields of metal-based catalysis for drug development and innovative delivery routes with cancer biology and immunology, applied to one of the deadliest cancers, glioblastoma (GBM), a fatal primary brain tumor for which no curing therapy exists, due to its location within the brain parenchyma and complex tumor microenvironment. Many potential drugs failed in the clinic due to their inherent toxicity and off-target side-effects, which add up to the challenges in reaching the protected brain site. Recently, innovative catalyst design enabled synthetic transformations in the presence of biological molecules. In Cat4CanCenter we will develop four innovative approaches to treat GBM. This new methodology requires the design of cage protected catalysts that will be delivered to targeted cell types using advanced lipid nanoparticle technology. Next, the catalysts will convert nontoxic prodrugs into active drugs within the GBM bulk. Our groundbreaking strategy aims for successful therapies to treat glioblastoma, by developing complementary approaches to therapeutically tackle the complexity of this disease. The new strategies, catalysts and prodrIn this project we explore a new avenue to treat glioblastoma, which is the most difficult cancer to target. In a collaborative program we develop biomimetic transition metal catalysts (key expertise 1) that will be delivered using smart strategies such as lipid nanoparticles (key expertise 2) to generate cancer drug in vivo. The glioblastoma biology will be studies in detail (key expertise 3).

Mots-clés : supramolecular cage catalysis transition metal catalysis glioblastoma tumor micro environment
Projet ERC : TransFORM (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Université technique de Berlin — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 4691859.0 €

Translation – the fundamental process of protein synthesis catalyzed by ribosomes - has been extensively characterized from a biochemical, structural, and mechanistic perspective. However, how exactly the translation machinery operates as an interconnected system of millions of ribosomes in cells is poorly understood. Within the cell, ribosomes associate with a multitude of regulatory proteins forming a variety of specialized complexes and distributing across cellular space in a manner that depends on cell state. What is the specific composition of those complexes, their significance, and their functional role? How are they defined and regulated by subcellular compartmentalization? How do they change in response to cellular stress? Our TransFORM synergy team brings together experts in method development for in-cell structural biology and the biology of translation to allow us for the first time to attack these fundamental problems. Building on our prior achievements, we aim to synergistically develop novel methods of cryo-electron tomography with imaging across scales in conjunction with crosslinking mass spectrometry and integrative structural modeling for near-atomic structure determination directly in cells. TransFORM will determine the ribosome structural and functional states across the translation cycle in human cells, following distinct 40S, 80S, and disomal particles (80S+80S), in and out of polysomes and across different protein synthesis regimes. We will uncover structural and compositional changes and regulatory mechanisms across cellular space, in adaptation to perturbations by stressors and during viral infection. Our model systems will span from single cells to organoids. TransFORM will provide a detailed and comprehensive in-cell map of the essential process of protein synthesis while delivering innovative methods for the next-generation of in-cell structural biology.

Mots-clés : in cell structural biology,translation,human cell models,ribosomes,heterogeneity,structural biology,cell biology,cryogenic electron tomography,crosslinking mass spectrometry,structural modeling,integrative modeling
Projet ERC : MechVivo (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Helmholtz-Zentrum Hereon — Pays : Allemagne — Rôle : CO-PI
Acronyme de l'entité : HZG
Type d'entité : Recherche
Financement ERC de l'entité : 2728169.75 €

Computational biomechanics is a fast-growing area of science. However, many of its fruits have not yet been translated into clinical practice. The main barrier to the translation of computational biomechanics into clinics is the lack of information about patient-specific mechanical properties of biological tissues. There are some methods for partially assessing these properties, but they have substantial limitations. A major cause of these limitations is the operating principle of current approaches, which rely on the analysis of the response of a tissue to some form of mechanical loading in vivo. To overcome this bottleneck, we propose a paradigm change. We will develop a method to infer mechanical properties of soft biological tissues in vivo based on a fundamentally new operating principle. To this end, we will leverage the synergy of three scientific areas covered by the three principal investigators of this project: (i) magnetic resonance imaging (MRI), (ii) experimental biomechanics, and (iii) physics-informed machine learning. Specifically, we will develop a new type of subvoxel MRI relaxometry to probe tissue microstructure non-invasively and establish a combined experimental and computational framework that will uncover for the first time the mechanistic link between transcriptomics, microstructure, and mechanical properties of soft biological tissues in a detailed manner. By leveraging this information with novel physics-informed machine learning techniques, we will gain the ability to determine the mechanical properties of soft tissues from clinical MRI data and blood samples with unprecedented accuracy and completeness. Our approach will be a crucial steppingstone to translate biomechanical computational models into clinical practice at a large scale. As a proof of concept, we will demonstrate how our new method can support the diagnosis of heart failure with preserved ejection fraction (HFpEF), one of the most common causes of mortality and morbidity.

Mots-clés : biomechanics,solid mechanics,materials modeling,soft tissue biomechanics
Projet ERC : NEMESIS (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Université de Padoue — Pays : Italie — Rôle : CO-PI
Acronyme de l'entité : UniPd
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2945151.25 €

Focal brain disorders, including stroke, trauma, and epilepsy, are the main causes of disability and loss of productivity in the world, and carry a cumulative cost in Europe of about 500 billion euro/year. Now, physicians diagnose and treat these conditions as if they were caused by local dysfunction due to the pathological process. However, there is growing evidence that, in most neurological and psychiatric disorders, clinical symptoms reflect widespread network abnormalities. Normalization of such network abnormalities through “circuit-based” stimulation would therefore improve function. However, this form of therapy is currently limited by numerous factors: lack of knowledge about the underlying mechanisms and their behavioural relevance; inability to map these abnormalities onto single patients; and, most importantly, a principled understanding of where and how to stimulate the brain to produce functional recovery. ‘NEMESIS’, from Ancient Greek as “give what is due”, aims to “give an injured brain what is missing”, i.e., restore through stimulation normal activity in dysfunctional brain circuitries. By synergizing people, concepts, and technologies, NEMESIS will first characterize the effects of focal injury at multiple spatial and temporal scales (from whole brain to local circuits). Through the combination of observational (e.g., fMRI, EEG, calcium imaging, LFPs) and causal methods (e.g., electro-magnetic stimulation, optogenetics) NEMESIS will test the hypothesis that disconnected networks lie in a “sleep-like state” that impairs communication. Thirdly, NEMESIS will create whole brain models of structure/function to predict the effect of individual lesions and simulate novel stimulation protocols aimed at “re-awakening” the disconnected brain. Finally, proof-of-concept interventions that combine circuit-based stimulation and behavioural training, guided by modelling and animal studies, will be tested to restore normal activity, and so give back what is due.

Mots-clés : focal injury,brain networks,brain rhythms,sleep,slow wave oscillations,whole brain computational models,brain stimulation,brain connectivity,fmri,eeg,lfp,calcium imaging,tms,7t mri