Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : VASC-IMMUNE (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université Otto von Guericke de Magdebourg — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : OVGU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3163750.0 €

In this ERC Synergy Grant, we will characterize the vascular-immune interface in melanoma and glioblastoma and explore the perivascular niche as a site for local anti-tumor immune activation. Cancer immunotherapy has made tremendous progress in the last two decades, but a vast majority of cancer patients do not benefit from this progress yet. Refinement of established immunotherapies will undoubtedly increase response rates. However, conceptually brave new therapies must be developed to make additional breakthroughs. The tumor vasculature plays a key role in orchestrating anti-tumor immunity by regulating recruitment and activation of T-cell and other immune cells. We propose to make a detailed characterization of vascular immune landscapes in melanoma and glioblastoma and to utilize this to optimize vascular-immune crosstalk and immune response as a new breakthrough immunotherapy. This proposal builds upon new knowledge on how immune hubs can form around tumor vasculature, which to a large part is based upon novel findings and development by the applicants (1, 2) on the importance of perivascular antigen-presenting niches in activating, sustaining, and executing CD8 and CD4 T-cell-mediated immune attacks on cancer. We will develop tumor vessel targeting AAV vectors that can enable therapeutic induction of immune hubs in cancer. This new form of immunotherapy will be evaluated alone and in combination with established cancer immunotherapies. Combined, our research teams are in a unique position to achieve this goal. Synergistic advancements will be obtained by joining Dimberg’s expertise in the vascular and immune microenvironment in tumors (especially glioblastoma); Tüting’s expertise in tumor immunology and cell plasticity (especially melanoma); and Essand’s expertise in translational gene therapy and cancer immunotherapy. The project is timely, and if successful can bring immunotherapy to the next level, rendering new hope to millions of cancer patients.

Mots-clés : tertiary lymphoid structures,antigen presenting niches,high endothelial venules,stem like t cells,glioblastoma,melanoma,tumor vascular biology,tumor immunology,cancer immunotherapy,aav therapy,mouse models
Projet ERC : RevLogRedux (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université de Cambridge — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2200177.01 €

Bad arguments have never been in short supply. The same holds for the scholarly interest they have elicited both in their own right and as a cautionary tale about everything that can go amiss when we argue. This is hardly surprising. Asking what is wrong with flawed arguments is tantamount to investigating the very rules and principles of argumentation – only in reverse. Fallacy Studies have flourished in recent years (especially under the label of «critical thinking»). Without notable exception, the ever-growing literature on argumentative failures suffers from a conspicuous lack of interest in medieval fallacy theory – arguably one of the most creative stages in the whole history of argumentation theories. The standard story is that after Aristotle got off to a tentative start, the study of fallacies lay dormant until people at Port Royal and John Locke revived it. RevLog Redux will show that this narrative is misleading and will replace it with a new account which will bring to bear the full resources of medieval treatments of illegitimate argumentative moves within and across the Latin West and the Greek East, as well as in the Arabic and the Hebrew traditions. In an unprecedented attempt to explore how medieval authors discussed fallacies, RevLog Redux will lay the groundwork for more conscious and historically sound ways to describe, classify and theoretically assess the laws and flaws of argumentation. To that end, RevLog Redux will develop an integrated computational infrastructure to manage the wealth and complexity of data, information and knowledge the project is expected to produce: namely, AskSten (as in «Ask Sten Ebbesen»), a multi-layered virtual research environment whose digital archive, knowledge base, Semantic Web architecture and on-line deployment will dramatically enhance the formal expressivness and coherence of the project’s findings. AskSten will also include a curated open access Encyclopaedia of Illegitimate Argumentative Moves.

Mots-clés : medieval philosophy,history and analysis of logic and argumentation,cross cultural medieval intellectual history
Projet ERC : CircuitEvolution (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université de Cambridge — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1804331.25 €

Animals display remarkable diversity in their behaviors, yet very little is known about how nervous systems evolve to generate such variation. CircuitEvolution will answer two fundamental questions: 1. How does brain wiring change across species as novel behavioral traits evolve? 2. What core features of brain circuits are deeply conserved across species? We will use electron microscopy connectomics, the only method that enables unbiased, brain-wide structural analysis of the synaptic connectivity between all neurons. Building on recent rapid progress in Drosophila melanogaster, the frontier of whole brain connectomics, we will target drosophilids at a strategically selected range of evolutionary divergences. Two PIs (Cardona, Jefferis) are pioneers in Drosophila connectomics, and our third PI (Ruta) and collaborators (Prieto-Godino, Benton) have pioneered molecular genetic investigation of behavioral and circuit evolution across drosophilids. Crucially, with our fourth PI (statistical physicist, Sales Pardo), we will identify conserved and divergent neurons and circuits across increasingly distant species, developing new inference methods for connectome alignment, simplification, and neuron annotation. Working together on this project we can develop a new field of whole-brain comparative connectomics. With cutting edge technology, we will obtain and share multiple connectomes for 7 species. These unique datasets will allow comparisons across species, sexes and developmental stages and support three areas of biological investigation within this grant: olfactory circuits, courtship behavior and the conserved core of the insect brain. This will generate many hypotheses that will be tested experimentally by the PIs, collaborators and laboratories worldwide. The insights and methods will have a major impact on understanding conserved and evolving circuit function across phyla all the way to mammalian brains and impact the design of artificial intelligence systems.

Mots-clés : connectomics,neuronal evolution,neural circuits,drosophila,olfaction,sexual dimorphism,network analysis
Projet ERC : ClonEScape (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université de Cambridge — Pays : Royaume-Uni — Rôle : CO-PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 5935060.0 €

Epithelial cancers are thought to evolve through a competitive process of mutation and selection in which the serial acquisition of oncogenic mutations confers an increasing fitness advantage, culminating in neoplastic transformation, tumour invasion, and metastasis. This programme often initiates through a phase of field cancerization in which mutant clones expand within the context of physiologically normal-looking tissue. To mitigate the risks associated with field cancerization, protection strategies have evolved that resist mutant clone expansion, from the development of anatomical features that limit clone growth to the activation of genetic and immunological surveillance mechanisms. Yet, despite these insights, our knowledge of how oncogenes act alone or in combination to evade these protection mechanisms to drive clonal pathogenesis remains largely unknown. Here, by combining a unique genetic lineage tracing strategy with comparative single-cell genomics and quantitative modelling-based methods, we will define the mechanisms that mediate mutant clone competition. By placing an emphasis on the squamous and columnar epithelia of the GI tract, we will investigate whether and how injury and inflammatory cues, as well as ageing, enable tumorigenic clones to evade natural protection strategies, functioning as a “second hit” in driving field cancerization and neoplastic transformation. Finally, to explore the translational relevance of our findings, we will combine DNA sequencing, single-cell methods, and spatial transcriptomics with the design and genetic manipulation of state-of-the-art 3D organ cultures to investigate mutant clone dynamics in human tissue. By tracing the origins of clonal pathogenesis, these findings promise insights into the design of new prevention, detection, and treatment strategies, targeting the early stages of cancer progression.

Mots-clés : intestine,stomach,oesophagus,liver,lineage tracing,mutant clone competition,injury induced cellular reprogramming,regeneration,cancer,ageing,advanced mouse genetics,human organoids,comparative single cell genomics,theoretical modelling
Projet ERC : PSINumScat (Horizon Europe, appel 2024, Synergy grants)
Entité participante : University College de Londres — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : UCL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3489915.0 €

Designing fast and reliable algorithms to numerically simulate the behaviour of high-frequency acoustic and electromagnetic waves is a longstanding open problem in computational mathematics. Furthermore, these waves underpin a plethora of communication and imaging technologies; therefore any progress towards solving this problem will have wide impact.  The project aims to design, analyse, and implement in open-source software new methods for the numerical solution of high-frequency acoustic and electromagnetic wave scattering problems. These methods will be faster, more reliable, and more widely applicable than current state-of-the-art methods, with this improvement achieved by exploiting techniques from pure mathematics specifically designed to study high-frequency problems; these techniques are from the area of semiclassical analysis and are based on studying functions in phase space (the combination of physical and frequency space). Since both numerical analysis and semiclassical analysis of high-frequency wave scattering problems are mature areas of mathematics, it is surprising that these two fields have operated largely in isolation from each other, with essentially none of the deep insights about high-frequency waves from semiclassical analysis used in the design of numerical methods for these problems. This project will exploit this untapped potential and implement the resulting methods in the open-source multiphysics finite-element software FreeFEM (https://freefem.org/) in easy-to-use packages. These packages will be designed for researchers in the applied sciences and industry seeking to simulate the behaviour of high-frequency acoustic and electromagnetic waves.  These goals will be achieved by combining the expertise of the three PIs: JG, an expert in semiclassical analysis, ES, an expert in the numerical analysis of high-frequency scattering, and PT, an expert in scientific computing and the lead developer of FreeFEM.

Mots-clés : high frequency,scattering,helmholtz,maxwell,finite element method,boundary element method,domain decomposition
Projet ERC : PushingCell (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Institute of Science and Technology Austria — Pays : Autriche — Rôle : CO-PI
Acronyme de l'entité : ISTA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2516375.0 €

The ability of cells to sense environmental cues and respond to them by adjusting their shape and motion is fundamental for biological processes ranging from animal development to disease. Much is known about how cells sense and respond to the geometry and mechanics of their environment by adhering to and pulling on the substrate. However, recent studies demonstrated that cells also strongly depend on non-adhesive interactions with the environment and that they probe, sense and deform their surroundings by pushing into them. The goal of this project is to address the mechanisms controlling cell shape and cell-substrate interactions via pushing forces. We will focus on three levels of cell organization: 1. Nanoscale pushing: We will investigate how cells locally sense and respond to obstacles without adhering to them and quantify the associated forces. Using micro-engineered substrates and tissue mimics, we will molecularly and biophysically dissect, biochemically reconstitute and theoretically model the interface between an obstacle, the plasma membrane and the actin cortex. 2. Mesoscale cell mechanics: We will investigate how actin, microtubules and intermediate filaments collaborate to generate and extend mesoscopic cell protrusions that push by adhesion-independent mechanisms. We will combine cell biological experiments and optogenetics with modeling and bottom-up reconstitutions. 3. Global force balance: We will examine adhesion-independent mechanisms that allow a cell to coordinate competing protrusions, maintain its integrity and translocate in complex environments. Using biophysical measurements and local molecular perturbations, we will test models of long-range communication within cells. Our work will provide new fundamental insights into biological and physical principles underlying the control of cell shape, integrity and motility, which are key to most physiological processes from development and homeostasis to cancer, immune responses and regeneration.

Mots-clés : cell shape cell motility cytoskeleton actin microtubules membrane shaping proteins active gel
Projet ERC : MIDRASH (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Université de Tel Aviv — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2229938.75 €

MIDRASH aims to construct a groundbreaking interdisciplinary methodology for a global approach to the study of the treasure trove of medieval literary manuscripts in Hebrew script. Jews produced and consumed a prodigious cornucopia of texts in Hebrew, Aramaic, Judeo-Arabic and other vernacular languages, intertextually closely related like a mille feuille. The manuscripts constitute the unique remains of medieval Jewish literary culture, having survived - and witnessing to - centuries of migrations, persecutions and censorship. With the recent digitization of the extant manuscripts and with contemporary advances in computer vision, natural language processing and machine learning, the time is ripe for broad new studies into this manuscript culture. We can now study questions regarding their materiality, textuality, transmission and historical contexts on an unprecedented scale or heretofore beyond reach.  MIDRASH proposes a pioneering study of the extensive corpora of: (1) biblical manuscripts; (2) Midrash (late antique exegetical and homiletical commentary on the Bible); (3) medieval commentaries of the Bible and Mishnah; and (4) liturgical manuscripts. Only a small fraction have been transcribed, let alone studied. State-of-the-art and bespoke algorithms will be applied to resolve issues of reading order, code switching, and transcription errors. Once mechanically transcribed, known and unknown works will be identified and reconstructed and multilingual intertextualities discerned. The latest fine-grained paleographical techniques and trained neural networks will be brought to bear on questions of provenance and transmission. Philological methods and computational linguistics will be applied to questions of textual fluidity and evolution to further our knowledge of the production and transmission of Hebrew manuscripts and texts, their authors, scribes and readers, and enhance their role as the pivotal aspect of European and Mediterranean intellectual history.

Mots-clés : hebrew manuscripts,document analysis,nlp,computer vision,midrash
Projet ERC : EUROpest (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université Eberhard Karl de Tübingen — Pays : Allemagne — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 291250.0 €

Born from years of interdisciplinary collaboration, EUROpest aims to articulate the complex ways in which social-ecological systems shape epidemics. It builds on resilience and actor-network theories to advance its own eco-bio-social paradigm that embraces a multi-causal understanding of disease transmission and disease impacts on human societies and ecosystems. While striving to develop and validate a general theoretical model, it takes the well-documented and highly diverse world of late medieval and early modern Europe as its laboratory – investigating its interconnected climatic, cultural, demographic, economic, ecological, and pathogenic history. With regard to the latter, EUROpest assumes malaria, smallpox, tuberculosis and enteric diseases were major components of a disease baseline over which the most devastating disease, plague (Y. pestis), occurred. EUROpest will carry out regional case studies – from Spain to Lithuania, Greece to England – selected on the basis of available and procurable written, scientific and archaeological data. It will holistically consider the contexts of plague outbreaks identified in those regions, to understand how context both facilitated outbreaks and also shaped them, and their short- and medium-term impacts. EUROpest combines archival source analysis with archaeology, archaeogenetics, paleoecology and paleoclimatology, and subjects case studies to novel human-supervised machine-learning to identify the causal role of factors influencing regional outbreaks. As the contemporary imagination is guided in its understanding of epidemic disease by the outbreaks of the past, EUROpest’s contribution will be critical to developing more nuanced and realistic scenarios of future pandemics, academic as well as popular. With EUROpest PIs already engaging policy makers, the mathematical precision of the eco-bio-social analysis EUROpest proposes will help design more successful and targeted interventions for future pandemic response.

Mots-clés : adna studies,palaeogenomics,environmental history,interdisciplinary history,disease history,climate history,plague,smallpox,machine learning in historical applications
Projet ERC : RECAP (Horizon Europe, appel 2024, Synergy grants)
Entité participante : National Institute for Astrophysics — Pays : Italie — Rôle : CO-PI
Acronyme de l'entité : INAF
Type d'entité : Recherche
Financement ERC de l'entité : 4435625.0 €

The epoch of Reionization marks the last major transition of the Universe: approximately 400.000 year after the Big bang, the neutral intergalactic medium, mainly composed of hydrogen atoms, started to be ionized by high-energy radiation from the first cosmic sources, stars, galaxies. The onset, timeline and topology of the Reionization process are all tightly linked to the nature of the sources of ionizing radiation: by identifying and studying them we can gain fundamental insights into what shaped the evolution of the universe, from the smooth matter distribution of early times, as revealed by the CMB, to the wealth of structures, like galaxies and clusters of galaxies that formed at later epochs. Our project will exploit the critical synergies in expertise of the 4 PIs and their teams, from the modeling of the intergalactic medium ionization and metal enrichment, to detailed observations of the ionizing sources, to shed light on their properties, their environment and the complex energy and baryon exchange between them and the intergalactic medium. We will exploit new extensive datasets coming from state-of-the-art facilities, such as the recently launched JWST, present and future VLT instrumentation and ALMA. To support and drive the interpretation of these new observations, we will develop a novel algorithm to model a self-consistent non-equilibrium 3D multi-frequency radiative transfer through H, He, metals and dust and produce both large scale and zoomed-in simulations that can be readily compared to real data. The proposed research aims at making fundamental steps to decode the mysteries of Cosmic Dawn and solve some of the puzzles in our current theories of early galaxy formation.

Mots-clés : epoch of reionization intergalactic medium
Projet ERC : METRIQS (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université technique du Danemark — Pays : Danemark — Rôle : CO-PI
Acronyme de l'entité : DTU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 6068401.0 €

The quest to design materials with tailored properties is a driving force for new scientific and technological horizons and is critical for addressing the grand challenges of humanity. Our proposal introduces an innovative concept in condensed matter and materials science: heterostructures built upon the fusion of 2D van der Waals materials and freestanding transition metal oxides (TMOs), forming a new compound metamaterial where the interface itself plays a crucial and active role in the properties and functionality. Our strategy is threefold. First, by incorporating a 2D layer between two TMO crystals to prevent ionic-covalent bonding and disorder, we can stack the TMOs with a continuous, free choice of twist angle. This will dial in interfacial superstructures called moiré lattices, which impose profound changes in their physical properties. Second, the moiré lattices will ‘imprint’ ferroic orders in the interfacial 2DL, which then act as a spacer, lubricating layer, and sensing layer in one. Moiré engineering has so far been reserved for van der Waals materials, and with METRIQS, we seamlessly merge TMOs with van der Waals materials, creating a highly versatile hybrid platform, where the interaction strength, strain, and dislocation networks can be controlled. Moiré metamaterials are used to study valleytronics and correlated states, control skyrmions, realise spin-charge conversion devices, and control the nucleation of chiral molecules. Our most ambitious endeavour unfolds in the third phase, where we are committed to revolutionising material synthesis by design. This will be achieved through interface manipulation, employing a combination of static and dynamic techniques, including strain, light, and electric/magnetic fields, in conjunction with the precise control of the bilayer twisted oxide as a tuning knob. This project unites two separate scientific communities and material families, in a team with highly complementary skills, knowledge, and resources.

Mots-clés : metal oxides,perovskites,graphene,transition metal dichalcogenides,van der waals heterostructures,two dimensional materials,spintronics,valleytronics,correlated states,chiral molecules