Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MEFHISTO (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
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 : 1063125.0 €

Inflammation is a complex spectrum of processes whose outcomes range from cell killing to tissue regeneration. In this context, a major goal in immune oncology is the development of treatments that stimulate cytotoxic immunity while limiting repair in the tumor microenvironment (TME), as these approaches have the potential to synergize with available immunotherapies and provide benefit to otherwise resistant patients. Pancreatic cancer is a largely incurable disease, in which aberrant inflammation and profound immune suppression conspire to sustain disease initiation, progression, and immune escape. Accumulating evidence supports the view that tumor-associated macrophages (TAMs) are key orchestrators of the balance between cytotoxicity and regeneration, and thus represent promising therapeutic targets in pancreatic cancer. In MEFHISTO, we aim at elucidating the molecular control, the functional implications, and the therapeutic potential of the PGE2-MEF2A axis, a newly described pathway enabling selective control of inflammatory gene expression in macrophages. By combining advanced genomic analyses in human samples, functional experiments in preclinical models, and mechanistic studies in key cell types, this Proposal will expand our knowledge of the organizing principles of innate immune responses in tumors. The ensuing results may lead to novel combinatorial treatments for diseases, such as pancreatic cancer, that are refractory to immunotherapy.

Mots-clés : macrophages inflammation genomics
Projet ERC : SCRIBE (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
Entité participante : Université Pompeu Fabra — Pays : Espagne — Rôle : PI
Acronyme de l'entité : UPF
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999465.0 €

CRISPR development has enormously accelerated genetic engineering principles, and precise methods to modify small alleles (such as base or prime editing) are now available. However, generating large genomic changes still presents enormous challenges. Large modifications, such as gene transfers, are performed generally with viral vectors, which have been associated with toxicities in the clinic, and often lack versatility needed for basic science experimentation. Newer CRISPR-based techniques for gene transfer suffer from significant efficacy and safety problems when used for large message writing.  The overall goal of SCRIBE is to create new strategies for gene writing and define their molecular principles. These new writers will use RNA to both encode and transfer the message. The SCRIBE strategies will take advantage of the retrotransposon capacity for writing genes from RNA, and the precision of CRISPR in addressing specific sites of the genome. Thus, the “find” function will be dominated by CRISPR components, and “copy-paste” activity will be executed by retroelement components. To develop and optimize such a technology, we will use evolutionary analysis to select those retroelements with the highest activity and orthogonality, and modulate their message writing capacity by engineering their components. We will test various CRISPR and retrotransposon combinations, and adapt both of them to converge into a unified molecular machine. We will use artificial intelligence applied to protein design and a novel concept of synthetically oriented evolution to accelerate emergence of the new function. Finally, we will deploy new gene writing principles for RNA-based in vivo gene delivery.  In sum, we will develop a new family of tools for engineering life. The real breakthrough will be the establishment of gene writing as a simple and general method for both research advancement and applied purposes.

Mots-clés : gene writing,crispr,genetic engineering
Projet ERC : QUIN-PINEM (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental Constituents of Matter
Entité participante : Technion - Institut de technologie d'Israël — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Breakthroughs in electron microscopy over the past 15 years have introduced femtosecond laser-driven electron microscopes that probe matter and even hybrid light-matter polaritons with ultrafast time resolution. However, such systems still mostly extract classical properties of light and matter. This project will pursue the next frontier – extract quantum properties of light and matter, such as correlations and entanglement. We will develop a new concept of laser-driven electron interferometry for the goal of creating and measuring quantum correlations in the ultrafast regime.  Over the past 4 years, my group has shown how free electrons can interact coherently with light in photonic cavities and even get imprinted by the quantum photon statistics of light. Leveraging such interactions enabled us and other groups to develop theories and experiments for controlling the wave nature of individual electrons, creating coherently modulated electron wavepackets.  Here we will harness such coherent electron modulation to develop new microscopy modalities that can reveal important quantum properties of light, matter, and their interactions: We are going to make the first observation of quantum nonlinear optical dynamics of polaritons in 2D materials, to measure the quantum state dynamics in superradiant quantum dot ensembles, and to capture the spatiotemporal dynamics of correlated matter, such as the creation and annihilation of vortices in superconductors.  Toward this goal, we will develop a unique ultrafast free-electron interferometer operating at cryogenic temperatures. Exploiting the quantum electron-photon interaction in this system can create unprecedented many-electron entangled states that break classical limits in electron microscopy. Specially designed photonic cavities will amplify the entanglement and promote electron microscopy as a novel platform for fundamental studies of quantum information science.

Mots-clés : electron photon interactions,polaritons in 2d materials,nanophotonics,plasmonics,ultrafast transmission electron microscopy
Projet ERC : NEURO-LABS (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and Processes Engineering
Entité participante : Université de technologie d'Eindhoven — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1996143.0 €

Artificial intelligence has demonstrated unprecedented advances in pattern and image recognition and is widely expected to significantly increase progress in smart healthcare devices, but continues to rely on inefficient supercomputers, operating remotely. On the other hand, relevant information for these applications mostly exists locally at the physiological level. Smart personalised bioelectronic applications can be tailored to a specific and unique case – or person – with the ability to be adapted, trained and optimised over time.  In this ERC project, organic neuromorphic engineering is combined with bioelectronics to achieve a tuneable neuromorphic platform, locally monitoring and modulating biosignals for the dynamic and adaptive learning control of a proof-of-principle soft robotic actuator. Due to their compliant and non-linear characteristics soft actuators are difficult to model and thus present an ideal opportunity to demonstrate neuromorphic learning control. Organic electronic materials have been successfully implemented as building blocks in neuromorphic computing and bioelectronic applications. Particularly, mixed ionic-electronic conductors possess exceptional characteristics for use in biological environments.  At the interface between mechanical engineering, materials science, neuromorphic engineering and bioelectronics, neuro-labs will develop an organic neuromorphic platform, by optimisation of organic materials and circuits, and integration of sensors, neuromorphic devices, and microfluidics. We will develop a closed-loop adaptive biocircuit and demonstrate local tuning and neuromorphic learning control of a soft gripper. Finally, we will show optimised biocontrol of the gripper using biohybrid synapses modulated by the neurotransmitter environment, directly tuning the feedforward parameters in hardware. This will open a completely new field of adaptive neuromorphic biointerfaces and inspire a novel conceptual approach for learning control.

Mots-clés : organic neuromorphic devices,organic biohybrid synapses,mixed conductors,organic bioelectronics,microfluidics,soft actuators
Projet ERC : Smart Nanoparticles (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Technion - Institut de technologie d'Israël — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Aging, Aging, genetic, and environmental factors have increased the prevalence of patients with neurodegenerative brain conditions, with limited treatment modalities. One prerequisite for effective brain treatments is the ability to target next-generation medications, including RNA and protein drugs, to specific neurons and brain regions. Nanotechnology platforms offer new therapeutic avenues for targeting drugs to organs and cells; their implementation in neurodegenerative diseases is nascent. In this research program, we aim to advance far beyond the state-of-the-art and elucidate the molecular and structural characteristics for designing nanotechnology drugs that target and treat brain neurodegeneration. In preliminary studies, we show that the blood-brain-barrier (BBB) overexpresses disease-specific receptors during neurodegeneration, which enable targeted nanoparticles to cross the BBB and penetrate neurons. Albeit these findings, the magnitude, mechanism, and nanotechnological molecular pattern for brain targeting are lacking. To address this fundamental gap, we will use advanced computation and engineering concepts to develop 4D-brain-targeting nanoparticles, that cross the BBB intact to target specific neuronal populations and brain regions. Robotic synthesis, coupled with active learning algorithms will be used to construct nanoparticles with combinations of targeting moieties on their surface and evaluate their neuronal specificity. Supported microfluidic BBB apparatus will be used to screen the nanoparticles’ ability to target and cross the BBB. A track-and-seek radar system will locate the nanoparticles in the brain, directing localized robotic biopsy of the nanoparticles in the destination cells in the brain. To connect our findings to future clinical implementation, fMRI will be used to record the therapeutic activity of the nanoparticles in the brain. This program will provide the community with essential findings to allow brain-targeted therapeutics.

Mots-clés : nanotechnology brain targeting neurodegenerative diseases brood brain barrier
Projet ERC : NEPI (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Study of the Human Past
Entité participante : Université technique de Berlin — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1992181.0 €

The present project will contribute to research in the history and philosophy of science through extensive use of state-of-the-art tools from the digital humanities. The project will focus on an investigation of recent research practice in particle physics at the European Center for Nuclear Research (CERN) in order to gain a better understanding of how knowledge is generated and validated in very large scientific collaborations. The main working hypothesis of the project is that collective research processes can be characterized, in epistemologically relevant terms, through a bird’s eye view analysis of the collaboration’s internal communication. The internal communication will be reconstructed from born-digital documents (e-mails, internal wiki pages, etc.) which accrue in the research practice of the collaboration. Abstracting from the case study, the project will also develop historiographic guidelines that can be transferred to future epistemological studies of modern scientific collaborations. Last but not least, the project will contribute to the philosophy of collective knowledge generation, in particular to recent issues in “network epistemology”, by adapting the theoretical models to better fit important real-world cases.  Until recently, it was nearly impossible to capture large-scale and complex research processes, such as the ones at CERN, and make them accessible for epistemological analysis. Almost all the studies of the research practice at CERN or similar cases have so far been restricted to the analysis of published articles, selected interviews and participant observation. Accompanied by historiographic guidelines and practical strategies (both of which are lacking at the moment) for best practices in the history and philosophy of science based on born-digital sources, the application of digital tools and computational methods may finally help us attain a maximally comprehensive picture of recent research practice in particle physics and beyond.

Mots-clés : integrated history and philosophy of science,history of modern physics,digital humanities,social epistemology,history of recent science,scientific collaborations,discovery and justification,machine learning,social network analysis,high energy physics
Projet ERC : RadCrossSyn (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Université Gottfried-Wilhelm-Leibniz de Hanovre — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1987059.0 €

The synthesis of complex natural products has shaped the field of organic chemistry, with translational applications spreading further into medicinal, agrochemical, and material sciences. As the largest class of natural products, terpenoids play a variety of roles in mediating antagonistic and beneficial interactions macroscopically, i.e., among organisms, and microscopically, i.e., on a (sub)cellular level. They defend many species of plants, animals, and microorganisms against predators, pathogens, and competitors, and they are involved in conveying messages within these organisms. Facilitating and streamlining the access to the most complex terpenoids, heavily rearranged and highly oxidized triterpenoids, requires an understanding of Nature’s ways to biosynthesize these structures, i.e., of their biogenesis. Biomimetic synthesis can only then provide routes which outrival classical retrosynthetic planning. In the absence of a plausible biogenesis proposal, this strategy is not accessible, though. So far, biogenesis proposals have, in lieu of validated intermediates and enzymes, followed the paradigm of polar mechanisms and evoked standard textbook reactions involving ionic intermediates to account for skeletal rearrangements. The aim of this project is to disprove this paradigm and cross this perceived limit of reactivity. Thus, we will here provide chemical proof that terpenoid biogenesis is not sufficiently explained by polar mechanisms, but rather is an intricate interplay of radical and polar reactivity. The border we attempt to cross is the one between two very different chemical entities: radicals and ions. Development of radical-polar crossover logic will evolve robust and selective routes to access drugable triterpenoid natural products modulating the immune system, targeting cancer, and combating pathogens. Added value comes from the involvement of modern photoredox catalysis strategies to initiate radical-polar crossover cascades in sustainable fashion.

Mots-clés : natural product synthesis,biomimetic synthesis
Projet ERC : FEVER (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Study of the Human Past
Entité participante : Université de Heidelberg — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1730895.0 €

Fever is one of the most basic and pervasive of human experiences. Even before the current COVID-19 pandemic took this to new extremes, fever and the attendant sensations – of ‘burning up’, or having one’s temperature taken – had long been familiar to men, women and, indeed, children. While fever is a universal feature of humans’ material existence, however, its relevance and meaning differed from one historical context to another. The proposed ERC project studies fever globally, particularly in societies within or tied to the Atlantic world, in the century spanning from the 1750s to the 1840s – a time when fever was not only considered the most common ailment that afflicted mankind, but also its most fatal one; ‘more persons died of fever than of all other ailments combined’, as contemporaries saw it. Given that fever was a threatening, ubiquitous presence for men and women around 1800, we know surprisingly little about it; as one medical historian recently put it, ‘fever has been the invisible elephant in the china shop of the medical past’. Premised upon archival research in countries across the world, the various subprojects expose and explain the unusual prevalence of fever in the period’s medical record; its persistent association with particular, ‘insalubrious’ environments rather than contagion; the unceasing relevance of vernacular, ‘folk’ and indigenous fever remedies in many Atlantic societies; and fever’s resonance and relation with similar disease concepts in other, non-European empires. The project also breaks new ground methodologically in its global, ‘new materialist’ and interdisciplinary approach – its dialogue with the medical sciences, history and philosophy of science, and environmental studies. It poses questions fundamental to our understanding of both the past and the present: about the rise and fall of diseases, the credibility of medical knowledge, and how cultural and historical contexts affect suffering and physiology, and vice versa.

Mots-clés : disease,global,indigenous,contagion,atlantic
Projet ERC : DNAStorage (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and Communication Engineering
Entité participante : Technion - Institut de technologie d'Israël — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999096.0 €

DNA-based storage has attracted significant attention due to recent demonstrations of the viability of storing information in macromolecules. Unlike classical optical and magnetic storage technologies, DNA-based storage does not require electrical supply to maintain data integrity, and given the trends in cost decreases of DNA synthesis and sequencing, it is estimated that within the next decade DNA storage may become a highly competitive archiving technology. However, existing coding solutions to address various problems associated with implementations of DNA-based storage systems are very limited in their development. The goal of this research is to develop coding methods and techniques by designing novel and advanced solutions that are specifically targeted for the unique structure and error behavior of DNA-based storage systems. The proposed analytical framework will allow to address coding-theoretic challenges arising in the context of synthesis, storage, and sequencing of DNA strands. To achieve these goals, we aim to design codes for clustering, trace-reconstruction techniques, error-correction codes, and constrained codes. These codes are applicable for long-term storage and recovery of data recorded in DNA, while overcoming the unique challenges associated with the DNA storage channel. We expect that knowledge, techniques, and qualitative insights gained in our investigation will advance DNA storage technologies capable of accommodating the massive amounts of data. Furthermore, solving the proposed coding problems will require new methods and ideas that will also impact adjacent scientific disciplines such as bioinformatics, combinatorics, and theoretical computer science. Thus, the proposed investigation is likely to lead to the development of new paradigms and directions of research that may have far-reaching societal and economic impact. Lastly, the accompanying experimental testing will allow for practical as assessments of system performance and cost.

Mots-clés : coding theory,error correcting codes,constrained codes
Projet ERC : X-MAPS (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
Entité participante : Université de Newcastle upon Tyne — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : Université de Newcastle
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999695.0 €

Black hole (BH) X-ray binaries (XRBs) radiate a huge X-ray flux from the BH vicinity. The X-ray signal, radiated by a hot corona and a cooler disk, contains information on the BH mass and spin, and the strong gravitational field close to its horizon. However, the X-ray emitting region is unresolvable, necessitating indirect mapping techniques. I pioneered forward-modelling spectral-timing techniques that exploit rapid spectral variability, and played a key role in the first studies of X-ray polarization. X-MAPS will take the novel and transformational step of combining these two powerful diagnostics into polarimetric-spectral-timing. This requires a huge increase in the computational intensity of my state-of-the-art models that my group will enable with machine learning to achieve the following science goals:  1) Understand state transitions: We will constrain how the structure of the disk-corona system evolves as the spectral shape changes and large-scale transient jets are launched, informing on the jet launching mechanism and thus how supermassive BHs influence their host galaxies.  2) Measure BH mass: The current observational picture that BHs in gravitational wave (GW) sources are heavier than those in Galactic XRBs has deep implications for binary evolution theory. We will make BH mass measurements using the X-ray signal alone, enabling measurements for XRBs inaccessible to traditional optical techniques (~70% of the population), which are thought to harbour heavier BHs. This will enable us to test the importance of observational bias in the comparison of XRBs with GW sources.  3) Measure 3D BH spin orientation: I recently found strong evidence that quasi-periodic oscillations (QPOs) observed in the X-ray flux of XRBs are driven by relativistic precession of the corona around the BH spin axis: variation of X-ray polarization with QPO phase. We will reconstruct the precession cone and thus the BH spin vector, providing new insights into binary evolution theory.

Mots-clés : black hole astrophysics