Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : BEMOSAIC (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Institut Weizmann — Pays : Israël — Rôle : PI
Acronyme de l'entité : WIS
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3863730.0 €

Endothelial cells (ECs) form a dynamic monolayer lining the lumen of vessels. While single-cell data have revealed high degrees of heterogeneity amongst ECs at the inter- and intra-organ levels, the prevailing notion has long been that vessels themselves are composed of largely similar ECs. Instead, data from our labs challenge this view by showing that vessels are built of highly diverse ECs displaying different behavioral properties, a feature we term intravessel EC behavioral mosaicism. While these findings are promising, there is still much to learn about the range of behavioral variability among ECs within vessels and how this intricate mosaic of behaviors is orchestrated to optimize vascular function. Building on our past achievements, we now aim towards novel directions- to push forward a fresh conception of vessels, as mosaic composites of specialized ECs. Here, we will integrate our synergistic expertise in live imaging, sophisticated genetic approaches, and spatial omics to map EC behaviors in zebrafish and mice. In addition, we will harness oncogenic mutations causing vascular malformations in humans to investigate how they alter the behavioral map. Finally, we will decode mechanisms of vessel tolerance and co-optation in response to stochastic expression of mutations to understand how vessels cope with EC mosaic behaviors. The important and unique aspects of our approach are the focus on in vivo dynamics and the cross-animal and organ comparisons, which will provide much needed knowledge on vessel architecture and function, making substantial advances at the frontier of vascular biology. Overall, we envision that shifting the paradigm of vessel heterogeneity to behavioral mosaicism will provide a better understanding of vascular-related pathologies and will lay the foundation for improving vascular therapies by targeting specific EC subsets. Moreover, we expect to offer means to understand other diseases involving mosaic responses, including cancer.

Mots-clés : endothelial cells,vessels,vascular malformations,live imaging
Projet ERC : CoTransComplex (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Université de Heidelberg — Pays : Allemagne — Rôle : CO-PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3138221.0 €

Most proteins function within larger complexes. How these intricate structures are correctly formed is poorly understood, yet critical to all cellular processes and pathological conditions. Recent breakthroughs suggest that multi-protein complexes form co-translationally, by super-assemblies of multiple ribosomes and other cofactors that are coordinated in time and space. This striking notion contrasts starkly with textbook models and is key to the possibilities and failures of complex formation. However, owing to technical limitations, the mechanisms and scope of actively coordinated protein assembly are poorly understood. Elucidating how these large and transient co-translational formations produce protein complexes throughout the genome is a next-level challenge that cannot be addressed by a single discipline. We propose a unique merging of cutting-edge approaches: 1) Ribosomal profiling to detect interactions between ribosomes engaged in assembly and cofactors genome-wide, 2) Single-molecule force spectroscopy and super-resolution imaging to reveal ribosome movements and nascent chain assembly. 3) Cryo-EM and tomography to elucidate the structural basis of ribosome interactions that enable direct assembly. Our program addresses 1) the coordination of multiple ribosomes in time and space, 2) the folding and assembly of nascent chains, and guidance by chaperones and novel cofactors, 3) the major protein complexes classes of homo-dimers, higher-order oligomers, hetero-dimers, and complexes formed at membranes. This ambitious program will provide insight of unprecedented detail and scope, spanning from the cellular to the atomic level, from in vivo to in vitro, from genome-wide patterns to molecular mechanisms, and from bacteria to human cells. It will impact a vast spectrum of protein complexes, reveal unknown layers of control in protein biogenesis, with implications for ribosome quality control, artificial protein design, and mechanisms of disease.

Mots-clés : co translational protein folding and assembly,translation,ribosomes,chaperones,cryo em,single molecule biophysics,ribosome profiling
Projet ERC : CONCERT (Horizon Europe, appel 2025, Synergy grants)
Entité participante : AREA Science Park — Pays : Italie — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 500000.0 €

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 : STARMORPH (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université suédoise des sciences agricoles — Pays : Suède — Rôle : CO-PI
Acronyme de l'entité : SLU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2798692.0 €

STARMORPH is a ground-breaking endeavour with the ambitious goal of understanding plant organ morphogenesis, which will pave the way to engineering plant growth. This is of paramount importance for enhancing agricultural and forestry yields and hence contributing to global food security and environmental sustainability. Plant organ morphogenesis involves differential growth, where various organ parts expand at different rates to create specific structures. A significant challenge lies in understanding these differential growth programs while considering the mechanical constraints imposed by the tissues. The plant hormone auxin plays a central role in differential growth. It forms concentration gradients within tissues, dictating the direction and rate of cell expansion. Mechanistically, auxin can either repress or promote growth in a tissue and concentration-dependent manner, but this biphasic behaviour remains largely unexplained. The extracellular space, cytosol, and nucleus have distinct auxin perception mechanisms and hence STARMORPH pitches an "auxin signature" concept, considering nuanced auxin levels in each compartment specifying an ensemble signal with quantitative and qualitative cell responses for morphogenesis. Currently, auxin subcellular compartmentalisation is poorly understood, and a key focus of the project is to provide a subcellular map of auxin dynamics within a growing organ to uncover how tissue mechanics interact with auxin-dependent growth processes, which will be pivotal for understanding plant morphogenesis. The STARMORPH project leverages a unique combination of plant, cell and synthetic biology, genetics, biophysics and organic chemistry expertise. This interdisciplinary collaboration aims to dissect plant morphogenesis from molecular to organ scales and has the potential to revolutionise our understanding of plant growth and development, with applications in biotechnology and plant engineering.

Mots-clés : morphogenesis,plants,auxin signature,cell wall,mechanochemical constraints,organelles,multiscale biology,hormone quantification,biosensor engineering,developmental plasticity,differential growth,signal integration,apical hook,interdisciplinary
Projet ERC : SHAPINCELLFATE (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Istituti di Ricovero e Cura a Carattere Scientifico — Pays : Italie — Rôle : Partner
Acronyme de l'entité : IRCCS
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 321375.0 €

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 : BlackHolistic (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Université Radboud de Nimègue — Pays : Pays-Bas — Rôle : CO-PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 7510973.0 €

Black holes (BHs) are icons of the fundamental nature of gravity, the mysterious force shaping the Universe. They are also the Universe’s most efficient power houses, turning infalling gas into energy and outflows that, together with gravity, mould galaxies and thus ultimately stars and planets. The first image of a black hole by the Event Horizon Telescope (EHT), wherein we played a leading role, captured the imagination of scientists and the public alike. This picture of the immutable black hole is however blurred by the dynamic, still mysterious behaviour of the surrounding gas. Our limited understanding of these turbulent, magnetised plasma in/outflows, producing the radiation and high-energy particles we observe, obstructs a straightforward interpretation of the black hole image for testing theories of gravity. The challenge in understanding the astrophysics of black holes and their impact on the cosmos is that they span >8 orders of magnitude in mass, size and timescales, and emit light over 15 orders of magnitude in frequency. Our new approach overcomes this scale separation, by simultaneously addressing the dynamics of large and small black holes, in colour. We produce for the first time high-resolution multi-colour movies with the EHT combined with new telescopes probing the variable extremes of the electromagnetic spectrum (e.g., CTA, MeerKAT/SKA1). The data are analysed and interpreted with innovative models finally combining micro- and macrophysics. The PIs bring together complementary expertise over the entire black hole mass scale in radio imaging and multi-wavelength monitoring, astroparticle physics, and theoretical modelling to bear on the problem. This is accompanied by four major investments: construction of a new mm-wave telescope in Africa enabling full dynamical imaging of black holes with the EHT, new model development, supercomputing hardware, and a vibrant team of young scientists to help develop a new, truly universal black hole paradigm.

Mots-clés : black holes,event horizon telescope,radio astronomy,vlbi,grmhd simulations
Projet ERC : MakingBlood (Horizon Europe, appel 2024, Synergy grants)
Entité participante : CERCA Institution — Pays : Espagne — Rôle : CO-PI
Acronyme de l'entité : CERCA;I-CERCA
Type d'entité : Recherche
Financement ERC de l'entité : 2076500.0 €

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 : GRAVITES (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Université de Vienne — Pays : Autriche — Rôle : CO-PI
Acronyme de l'entité : Uni Wien
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 4337782.5 €

The four known interactions that occur in nature can be described either by Einstein's general relativity or by quantum field theory. Over the last decades physicists have tried to put these two pillars of modern physics on a common foundation. In doing so, they have been limited by a lack of experiments at the interface of these two frameworks. Both theories have been independently verified with astonishing precision, but all verifications to date have come without drawing on concepts from the other theory. The goal of GRAVITES is to perform experiments at the interface of quantum physics and general relativity. For the first time, we will measure gravitational properties of single and entangled photons in the background of Einstein’s gravity. To this end, GRAVITES aims to combine four complementary disciplines: quantum photonics and precision interferometry guided by expertise in general relativity and quantum field theory. The synergy among the research groups will realize a large-scale fiber interferometer with unprecedented precision. Since the sensitivity of GRAVITES’s apparatus must exceed present large-scale fiber-based quantum interferometers by orders of magnitude, the two experimental teams must combine cutting-edge technologies in their respective fields for advancing single-photon interferometry. These developments are also of direct relevance for many other applications such as quantum metrology and quantum sensing. In parallel, the theory teams will investigate the combined effects of gravitation and field quantization in dielectric waveguides. With this united effort GRAVITES is in the position to explore new physics that determines the gravitational properties of quantum superposition and quantum entanglement. This will allow us to create a unique experimental platform for probing how gravity interacts with the quantum world.

Mots-clés : quantum photonics,quantum gravity interface
Projet ERC : MANTRAMS (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Université Eberhard Karl de Tübingen — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2840397.0 €

Over 4 million people in Europe, including Hindu, Buddhist, Sikh minorities and Yoga practitioners, use mantras—sacred utterances, formulas, or syllables—for the purposes of ritual, prayer, contemplation and wellness. The term “mantra” itself has entered the vocabulary of most modern European languages. But how do mantras work? Where do they come from, and how did they spread around the globe? Despite their ubiquity and relevance, mantras have seldom been studied in their own right. This project will produce an unprecedented global history and anthropology of mantras, grounded in the PIs’ expertise on the very places and traditions where mantras originate–southern Asia, where mantras have been used in rites, meditation, worship, and healing for more than 3000 years. As mantras have been transmitted through diasporic networks, new religious movements, yoga and the internet, they have become central to religion and culture worldwide, while they also play a key role in traditional medicine and identity politics. Most scholarship to date has approached mantras through language and philology, privileging Sanskrit texts from elite contexts. Yet mantras have always been diverse, multimodal and multisensory, manifesting in manuscripts, on stones, in the voice through chanting, in the mind through meditation, and on the body through amulets, tattoos, and clothing. Bringing together leading scholars working across disciplines and cultural regions, this 6-year project will create sonic, visual and digital textual archives on the transcultural and multisensory lives of mantras, together with an exceptional array of academic deliverables and a museum exhibition. Raising awareness of mantras’significance from their origins in ancient South Asia to their modern ramifications in the global North, the MANTRAMS project will produce the first-ever scientific project entirely dedicated to understanding the relevance of mantras at a global scale.

Mots-clés : asian studies indology sound studies cultural anthropology
Projet ERC : CODICUM (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Royal Danish Library — Pays : Danemark — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 342113.75 €

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