Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : GOVERNA (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : Société Max-Planck pour le développement des sciences — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : Société Max Planck
Type d'entité : Recherche
Financement ERC de l'entité : 2171250.0 €

Eukaryotic messenger ribonucleoprotein (mRNP) particles are the functional entities that carry genetic information to the protein synthesizing machinery. These ribonucleoprotein complexes are dynamic and diverse, as highlighted by the copious number of proteins and transcripts identified in global proteomic and transcriptomic studies. However, little is known about the composition and architecture of individual mRNPs, and how changes in mRNP structure relate to their function or to dysfunction. The GOVERNA project will address this gap in knowledge by purifying specific mRNPs and delving into their molecular and structural arrangement. With our preliminary data serving as a springboard, the project combines genomic tagging engineered to maintain the most physiologically relevant conditions, biochemical methods developed to preserve the integrity of transient ribonucleoprotein assemblies, and mass spectrometry and cryo-electron microscopy to identify the composition and architecture of mRNPs. We will zoom-in on a set of paradigms in RNA biology that not only sample the breadth of mRNP diversity, but are also powerful model systems for linking structural information and biological function. We will investigate the molecular features in the three-dimensional organization of nuclear mRNPs from S. cerevisiae and of translationally repressed mRNPs in early developmental stages in D. melanogaster and X. laevis. For mRNPs undergoing active translation, we will investigate the transitions of human beta-globin mRNPs in the course of a surveillance process connected to disease. By studying these examples, we will glean fundamental insights into global principles governing the packaging of mRNPs and the remodeling of their three-dimensional features throughout a transcript’s life-cycle. The cumulative output will illuminate a central node of eukaryotic gene expression that is also particularly timely and relevant given recent developments in mRNA-based therapeutics.

Mots-clés : messenger ribonucleoproteins rnp,mrna transport and localisation,mrnp maturation
Projet ERC : Stellar-BHs-SDSS-V (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
Entité participante : Société Max-Planck pour le développement des sciences — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : Société Max Planck
Type d'entité : Recherche
Financement ERC de l'entité : 2855000.0 €

Stellar evolution models suggest that there ought to be ~10e7 stellar-mass black holes (BHs) in our Milky Way. However, we currently know only of ~20 BHs, and those are in binaries where accretion makes them shine in X-rays. Beyond that, no non-accreting ‘dormant’ BH has ever been robustly identified across the Galactic disk. Finding dormant BHs in binaries (dBHBs) is fundamental to learning when which BHs form, how massive stars die, and what the precursors of BH gravitational wave events are. Such BHs cause characteristic time variations in radial velocity (RV), flux, and light-centroid positioning of their luminous companion, providing an avenue for detection and study. Spectroscopic, astrometric and photometric surveys now yield the data needed to search for dBHBs. Yet, recent dBHB candidates have instead turned out to be short-lived evolutionary phases of close binary stars: thus, any successful search for dBHBs must entail sifting through vast samples using a combination of these signatures, and rigorously eliminating ‘false positives’. I propose an unprecedented search for Galactic dBHBs that should find ~100 of them, drawing crucially on the spectra of ~580,000 massive stars from the SDSS-V survey. As SDSS-V project scientist, I have helped shape it as the only all-sky, multi-epoch spectroscopic survey, systematically focused on stellar physics. Novel analysis of these spectra will be meshed with detailed modeling of TESS light curves and Gaia astrometry. Through guaranteed-time, high-resolution follow-up spectroscopy on the candidates, we will get detailed RV curves and crucial ‘spectroscopic disentangling’ to identify false positives that have two luminous components. Either dBHBs do not exist in any numbers in our Galaxy, or this proposal will find and characterize them. Beyond the ‘risky’ search for dBHBs, this program will break ground in identifying numerous other dark companions to massive stars, such as white dwarfs or neutron stars.

Mots-clés : spectroscopic surveys spectral modelling
Projet ERC : SUPERMINT (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed Matter Physics
Entité participante : Société Max-Planck pour le développement des sciences — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : Société Max Planck
Type d'entité : Recherche
Financement ERC de l'entité : 3188750.0 €

Memories that operate at cryogenic temperatures are urgently needed to realize advanced quantum and superconducting computing systems that will enable more efficient and scalable computing systems beyond today’s reach. SUPERMINT proposes to combine the latest advances in superconductivity and spintronics to build a novel SUPERTRACK cryogenic memory, that is high performance, non-volatile and that needs very low energy for its operation. A major objective will be to demonstrate the generation and use of triplet supercurrents, that are dissipation-less, but which carry spin-angular momentum, to move chiral domain walls in magnetic racetracks. A second major objective will be to explore the origin and utilize our recent discovery of a non-reciprocal Josephson diode effect, to build a novel device to detect magnetic fields and thereby “read” magnetic domain walls for SUPERTRACK. These objectives will be met by exploring and designing “manufactured interfaces” or MINTs that combine superconducting and magnetic ultra-thin layers using an advanced complex of thin film deposition systems that I have constructed over the past 5 years. To achieve these objectives, fundamental breakthroughs are needed in the preparation of MINTs with high-quality interfaces. A wide-ranging exploration of MINTs formed from superconducting layers with chiral antiferromagnets, homo-chiral layers of chiral compounds, especially from the B20 family of materials, and geometrical chiral structures will be undertaken. In addition, the concept of obstructed atomic insulators that we have recently developed will be used to identify novel interfaces of insulating materials that are metallic and, thereby, to explore the possibility of making these superconducting by pairing electrons via chiral antiferromagnetic fluctuations in adjacent layers.
Projet ERC : DIMERCIRCUITS (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
Entité participante : Université de Naples - Frédéric-II — Pays : Italie — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 300000.0 €

Synthetic gene circuits offer considerable potential for engineering human cells to perform complex functions for innovative biotechnological and therapeutic applications. However, current approaches are limited by the lack of versatile, scalable and modular molecular components. DIMERCIRCUITS aims to overcome these barriers by developing a novel class of Modular Artificial Dimerizing transcription factors (MADTFs) whose activity is dynamically regulated through interaction with competitive inhibitory proteins (ΔTFs). These ΔTFs competitively heterodimerize with MAD-TFs preventing their homo-dimerization and thus their function. This dual strategy enables dynamic and reversible regulation of gene expression, establishing a novel technological platform to build synthetic circuits and program cell behaviour. The compact and modular design of MADTFs and ΔTFs not only facilitates their integration into a variety of biotechnological applications but also enhances their potential for clinical translation. Computational modeling and machine learning techniques will be employed to explore the design space of synthetic circuits based on these components, ensuring they meet desired regulatory functions. This framework will guide the experimental implementation of synthetic circuits in human cell lines. As a proof of concept, the therapeutic potential of DIMERCIRCUITS will be demonstrated in patient-derived organoids for the treatment of Friedreich's ataxia, a rare genetic neurodegenerative disorder. By engineering a gene dosage compensation circuit, DIMERCIRCUITS aims to achieve precise regulation of therapeutic gene expression within a narrow window, independent of viral vector uptake, thereby mitigating the overxpression-related toxicity risks associated with current gene therapy approaches. DIMERCIRCUITS aims to establish a foundational technology for precision-engineered synthetic circuits enabling transformative advances in both biotechnology and medicine.

Mots-clés : mammalian synthetic biology gene expression systems modelling control engineering gene therapy
Projet ERC : CHEMCONTROL (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : Radboud University Medical Centre — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : Radboud UMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2625000.0 €

Cognitive control enables us to flexibly adapt behaviour to achieve our goals given a constantly changing environment. It is a hallmark of the human mind and exquisitely vulnerable in health and disease. Cognitive control often implies goal-directed instrumental effort to inhibit unwanted, yet hardwired or overlearnt biases, and is commonly associated with the prefrontal cortex (PFC) and dopamine (DA). However, the mechanisms of the broader construct of flexible cognitive control remain unclear. The urgency of addressing this is evidenced by robust predictive associations between flexible control and consequential life outcomes for health, wealth and well-being. CHEMCONTROL approaches the problem from a novel angle, reconceptualizing it as meta-level decision-making between distinct control strategies. I propose to shift attention away from the classic focus on instrumental effort, implicating PFC and DA, towards a richer meta-control framework that takes into account outcome controllability. CHEMCONTROL radically upgrades the value of an opponent, cognitively effortless strategy that releases hardwired Pavlovian biases, implicating serotonin (5-HT). It redefines PFC function as making meta-level decisions between expensive dopaminergic versus frugal serotonergic strategies based on estimating outcome controllability. We have recently validated a computational procedure for quantifying controllability estimates. I will combine this procedure with (i) high-resolution fMRI to compare neural activity in DA and 5-HT systems and (ii) novel PET designs to compare DA and 5-HT release. Next, I will use (iii) psychopharmacology and (iv) ultrasound neuromodulation, to causally manipulate key model components. CHEMCONTROL will unravel the mechanisms of (boosting) meta-control, revolutionizing strategies for promoting efficacy and resilience in a rapidly changing world.

Mots-clés : cognitive control,dopamine,serotonin,functional neuroimaging,psychopharmacology,brain stimulation
Projet ERC : REVALVE (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
Entité participante : Radboud University Medical Centre — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : Radboud UMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Calcifying Aortic Valve Disease (CAVD) is a cellular-driven disease that actively alters the structure and composition of the valve extracellular matrix, leading to severe disfunction of the heart. Because the molecular mechanisms underlying CAVD are still unknown, there are currently no drug-based therapies and valve replacement is the only available treatment.  Specifically, it is still unknown (1) how the disease modifies the extracellular matrix (ECM) to become susceptible for mineralization, (2) how cell differentiation and matrix modification lead to calcification, and (3) how the mineral develops within the matrix. We lack these answers mainly due to our inability to characterize matrix development with the required chemical and structural details during the CAVD process. I aim to push our capability for in situ imaging of ongoing biological matrix formation processes from the micron to the nanometer scale by creating a designer tissue imaging platform for CAVD. This will be achieved by: • creating a human CAVD-on-a-chip that allows the application of mechanical and (bio)chemical cues to accurately emulate the early stages of CAVD; • designing the chip to accommodate a 3D correlative multiscale imaging and spectroscopy workflow to study matrix modification and mineralization in the native state from the micrometer to the nanometer scale; • developing a method to (1) collect cryo-sections from the ECM created at precisely selected points in space and time, to (2) transfer these to a transmission electron microscope and (3) revive -inside the microscope- the biological processes that are ongoing in the at the moment of cryo-arrest. This will allow for the first-ever dynamic nanoscale imaging of ongoing ECM processes.  These new capabilities will allow breakthroughs in understanding the role of matrix interactions in aortic calcification, opening the way for future development of drug-based treatments for CAVD.

Mots-clés : electron microscopy,correlative microscopy,volume em,3d cryoem,in situ em,raman microscopy,biomineralization,organ on a chip,aortic valve calcification,collagen
Projet ERC : TOPOMECH (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : IFOM — Pays : Italie — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 1041250.0 €

The nucleus is the stiffest organelle in the cell and is constantly challenged by intrinsic and extrinsic forces that deform the nuclear envelope. Chromosomes are mechanical objects that can sense, transduce and adsorb mechanical forces. Inter-chromosomal contacts and nuclear envelope-associated domains contribute to transduce mechanical stress when cells experience compression, stretching or interstitial migration. We aim to study the mechanical properties of the chromosomes and how genome integrity and the chromatin topological landscape are affected by nuclear deformations. We will combine mechanistic, genetic and genomic studies in yeast (WP1) with genomic, imaging and microfluidic approaches in mammalian cells (WP2). In WP1 we will investigate i) how the topological context influences nucleosome chirality and the epigenetic landscape; ii) how the inter-chromosomal connections mediated by topoisomerase activities influence genome mechanics; iii) how chromosome topology contributes to generate aberrant DNA structures and how DNA damage induces topological changes; iv) how the nuclear envelope and the nucleolus influence chromatin topology and histone modifications; v) how nuclear deformation affects genome integrity and the topological landscape. In WP2 we will study: i) the ATR and ATM-mediated mechanisms controlling nuclear and genome integrity and mechanics, under unperturbed conditions or in response to mechanical stress; ii) how the topological context of the genome responds to mechanical forces generated by cell compression or stretching and the implications for fragile site expression; iii) how mechanical stress generated by interstitial migration influences genome topology, chromosome instability, and those mechanisms causing amplification of specific chromosomal loci. The expected results may contribute to elucidate the mechanisms controlling nuclear and genome mechanics and those pathological processes promoting certain mechano-diseases.
Projet ERC : IN-ROME (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Study of the Human Past
Entité participante : Université de Rome « La Sapienza » — Pays : Italie — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 305356.25 €

Rome as the first-ever mega-city reaching c.1 million inhabitants in the early empire (1st cent. BCE), remains an enigma regarding the way it organised itself and maintained that size for over three centuries. Having long outgrown the 4th-cent. BCE city walls, the urbanistic structures that developed outside of these, and especially outside the later Aurelian Wall, have never been studied systematically and holistically. IN-ROME aims to fill this fundamental gap. It will describe for the first time how different parts of the population (ethnicities, status groups, genders) and their activities map onto the city’s surroundings via military stations, association seats, sanctuaries, production sites, mines, agriculture, retail, baths, guesthouses, tombs and villas. Translating topographical relations into social ones, it aims significantly to enhance our understanding of the city’s social fabric. Methodologically, IN-ROME breaks new ground by unlocking the enormous potential of inscriptions for our understanding of Rome’s urban development and social fabric through virtual re-contextualisation and statistical analysis. The authoritative Epigraphic Database Roma will be extended to include all Latin and Greek inscriptions with known or probable provenance (totalling c.50,000). They will be linked to Rome’s most sophisticated Digital Archaeological Cadastre, SITAR, via a newly created map layer of 17th-20th-cent. properties (the main historic reference to location). These new resources will allow the exploration of topographical patterns of activities on an unprecedented scale, revolutionising access to a vast pool of historic information and restoring Rome’s people back into their landscape. Outputs include six books and two international conferences with proceedings. The geo-referenced inscriptions and historic property map will be lasting resources beyond this project, and will radically transform a wide range of research from multiple disciplines.

Mots-clés : roman history roman archaeology epigraphy gis databases city of rome
Projet ERC : Timing-FreePhase (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental Constituents of Matter
Entité participante : Université Johann Wolfgang Goethe de Francfort-sur-le-Main — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2457443.0 €

Electron emission from matter is a widespread phenomenon in nature, with examples including the photoionization of atoms and molecules, photoemission from solids, and the release of electrons due to ionizing radiation in biology. Complete information about the emitted electrons is contained in the amplitude and phase of their wave packets. While state-of-the-art electron spectroscopy routinely accesses the amplitude of these wave packets, the phase of free electron wave packets remains inaccessible. My team and I aim to develop an experimental technique to measure the phase of free electron wave packets without interfering with their creation mechanism. This will be groundbreaking, as the phase of the free electron wave packet carries information about the quantum mechanical properties of photoionization and the electron in its bound state prior to ionization. We will accomplish this task by constructing a novel, microscopic, ultrafast free-electron-interferometer, in which replicas of the initial free electron wave packet are generated, shifted in momentum space, and brought to interference. At the heart of this innovative interferometric scheme are two crossed pulsed standing light waves that interact with the wave packet after its creation on femtosecond timescales. We will scale this approach to be applicable to correlated few-body wave packets by combining the light field interferometer with coincident multi-particle detection in a COLTRIMS reaction microscope. Employing this groundbreaking method, we will address three objectives: (1) We will investigate the time evolution of the phase of an atomic photoelectron wave packet with a linear and with a helical interferometer made from light carrying orbital angular momentum. (2) We will study wave packets emitted from molecules, including chiral molecules. (3) We will examine correlations and entanglement within two-electron wave packets and between photoelectrons and their parent ions

Mots-clés : photoionization,strongfield physics,attosecond science,tunnelionization,kapitza dirac effect,photoelectron spectroscopy in the gas phase,coltrims,reaction microscope
Projet ERC : StereoCPC (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
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 €

Stereoselective synthesis is a central aspect of modern organic chemistry, enabling the precise formation of specific stereoisomers in complex molecular architectures. Key to this process are reactive intermediates such as carbenes, radicals, and carbocations. However, achieving complete stereocontrol over non-classical carbocations in the stereoselective synthesis of acyclic molecules remains a formidable challenge. These fascinating carbocations, despite decades of research, exhibit unpredictable reactivity, making the controlled creation of stereocenters particularly difficult. In this proposal, our primary goal is to achieve comprehensive stereocontrol over non-classical carbocations. We plan to accomplish this by first identifying the specific substitution pattern necessary to generate these carbocations as a single isomer. Then, we will focus on precisely controlling their reactivity to form stereodefined adjacent C–X and C–C bonds at distant positions from the initial carbocation, through molecular rearrangement. This approach not only aims to tame the unpredictable nature of non-classical carbocations but also to harness their reactivities to create highly complex and defined acyclic molecular structures. Additionally, we aim to pioneer new strategies for synthesizing polysubstituted cyclobutanes, and strained fused ring system utilizing bismetalated species, an accomplishment that has never been achieved, despite the growing use of these structures as potential bioisosteres. These methods represent a significant advancement in the stereocontrolled synthesis of complex molecules, addressing longstanding challenges in regioselectivity, substitution patterns, and stereochemistry. By harnessing the unique reactivity of strained rings and non-classical carbocations, this research is set to unlock novel pathways to molecular architectures previously deemed unattainable, significantly enriching the synthetic toolbox of organic chemistry.

Mots-clés : non classical carbocation,stereochemistry,acyclic systems,cyclopropyl carbinyl cation,nucleophilic substitution,cyclobutene,housane,bicyclobutane,bicyclopentane,gembismetallated species