Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ChromaChrono (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : Institute of Science and Technology Austria — Pays : Autriche — Rôle : PI
Acronyme de l'entité : ISTA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1624563.0 €

Transcription factors (TFs) distinctly mark regions of the genome for expression and are the pillars of cell identity. Yet, even at the basic level of DNA recognition by TFs, we know very little about how this is achieved. In eukaryotes, all DNA-templated processes occur in chromatin; however, most studies elucidating the molecular mechanisms of transcription have been performed on histone-free DNA. In the proposed project, we will use TFs as centerpieces to understand how, in the circadian system, the interplay between transcriptional regulatory complexes and chromatin shapes the eukaryotic genome to control gene expression. Specifically, we will use biochemical approaches paired with functional genomics and cryo-EM (single particle and tomography) to investigate how histone identity affects TF-DNA engagement and how TFs and histone modifications influence chromatin organization across biological scales, from nucleotide sequence to chromatin structure in situ. We will exploit circadian time in mammalian cells and the unicellular green algae, Chlamydomonas to elucidate the dynamic gene regulation of a biological system under natural conditions. Using diverse model organisms will enable us to reveal common, conserved properties and processes. Ultimately, these studies will provide unique insight into the fundamental mechanisms of gene regulation while dissecting the molecular mechanisms of biological timekeeping.

Mots-clés : chromatin,transcription factors,cryo em,circadian
Projet ERC : INF_2 (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer Science and Informatics
Entité participante : Institute of Science and Technology Austria — Pays : Autriche — Rôle : PI
Acronyme de l'entité : ISTA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1662400.0 €

Extracting information from data is the key challenge of our time, and in many applications (e.g., genome-wide association studies, data compression, and virtual assistants such as ChatGPT) both the data and the machine learning model used to extract information are increasingly high-dimensional. As traditional statistical theory is ill-equipped to face this explosion in the dimensionality of the problem, machine learning is now predominantly experimental. However, empirical approaches come with huge costs affordable only to large companies, and they lack interpretability, which is especially troublesome in medical applications. To address these issues, the INF^2 project develops information-theoretically principled methods for high-dimensional inference in machine learning and data science. The key insight is that, via a “mean-field” approach, high-dimensional quantities are well approximated by low-dimensional ones and then characterized exactly. Leveraging this characterization, we will (i) establish the fundamental limits of inference, i.e., the minimal amount of data necessary to solve the problem, and (ii) design efficient algorithms requiring only the minimal amount of data. The challenge we tackle is to apply this paradigm to practical settings, in which data are structured and heterogeneous (as in genome-wide association studies), and models consist of complex architectures tailored to applications (auto-encoders for data compression, and transformers for ChatGPT). Through a novel analysis of spectral methods, approximate message passing and gradient descent, INF^2 builds a theoretical framework having conceptual impact, as well as vast applicability, in machine learning and information theory. This framework is then brought to the real world via applications in genome-wide association studies. Broadly, our results enable the principled design of machine learning algorithms and models, drastically reducing costs and providing interpretable solutions.

Mots-clés : theory of machine learning,information theory,high dimensional statistics,genome wide association studies gwas,approximate message passing amp,spectral estimators,neural networks,mean field analysis
Projet ERC : MEGI CD (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Innsbruck Medical University — Pays : Autriche — Rôle : PI
Acronyme de l'entité : MUI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1493875.0 €

The rising incidence of inflammatory bowel diseases such as Crohn?s disease (CD) has become a global health care issue in the 21st century. The complex genetic underpinning is increasingly appreciated, while environmental cues and specifically a Western diet are suspected to impact development and course of disease. Mechanistic insights that would support this assumption remain scarce and specific nutrients that trigger a flare are unknown. Westernisation of dietary habits is partly characterised by enrichment of long-chain fatty acids, which fuel metabolic inflammation of tissues beyond the gut. Here, we propose to establish the concept of metabolic gut inflammation as a fuel for CD. By analysing transgenic mice, human CD organoids and two independent CD patient cohorts, we seek to establish how dietary polyunsaturated fatty acids (PUFAs) affect gut inflammation and disease course. The proposed work is based on our previous observations that dietary PUFAs trigger a chemokine response and Crohn?s-like enteritis in mice, which is restricted by intestinal epithelial Glutathione peroxidase 4 (GPX4). GPX4 is an evolutionary conserved anti-oxidative enzyme which shows impaired activity in CD epithelium. The proposed work will identify how dietary PUFAs elicit gut inflammation in mice and which epithelial lineage executes the inflammatory response. In a next step, I propose to establish a critical crosstalk between GPX4 and metabolic hubs in gut epithelium to provide a basis for the concept of metabolic gut inflammation. Finally, we seek to translate findings by establishing that PUFAs evoke an inflammatory response from CD epithelium, and that PUFA intake impacts disease course. MEGI CD comprehends basic and translational science to set the basis for novel therapeutic strategies in a complex illness that requires better treatment modalities. The study will prove the concept of metabolic gut inflammation as a major driver of human CD, a basis for nutritional therapy.
Projet ERC : ConFine (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Université de Pise — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1383554.75 €

The interaction between microscopic and macroscopic quantities lies at the heart of fascinating problems in the modern theory of nonlinear PDEs. This phenomenon, modeled by weak forms of convergence, entails the formation of oscillations, concentrations, and fine geometric patterns ubiquitous in geometric, physical, and materials science models. ConFine will investigate the nature of concentrations and fine geometries arising from longstanding conjectures and novel questions of the calculus of variations. The goals comprise two themes. Theme I examines the qualitative and quantitative nature of PDE-constrained concentrations. Building upon results recently pioneered by the PI, its purpose is to prove a novel interpretation of Bouchitte's Vanishing mass conjecture, and novel compensated integrability results, with profound implications for the compensated compactness theory. Theme II investigates the fine properties of PDE-constrained measures from three different perspectives. Via potential and measure theory methods, it will attempt to produce substantial advances towards solving the sigma-finiteness conjecture in BD spaces. It will also investigate the structure integral of varifolds with bounded first-variation. The goal is to prove that these measure-theoretic generalizations of surfaces possess an underlying BV-like structure. Lastly, Theme II conjectures a complementary result to the ground-breaking De Philippis--Rindler theorem, which asserts that the regular part of an A-free measure is essentially unconstrained. This set of problems comprises significant theoretical obstacles at the forefront of the calculus of variations and geometric measure theory. In this regard, the proposed methodology gathers novel ideas oriented to overcome such paramount challenges. Consequently, far-reaching implications beyond the proposed objectives are expected, in the development of new methods and applications, in diverse fields of Analysis.

Mots-clés : calculus of variations,geometric measure theory,compensated compactness,fine properties
Projet ERC : MeMori (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : Université d'Aarhus — Pays : Danemark — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1547500.0 €

Atmospheric CO2 levels are affected by sources (industrial processes, respiration) and sinks (carbon fixation, storage of organic carbon). Viruses that infect microorganisms may play an important role in soil carbon sink properties. In soil, carbon is stored, or sequestered, by binding to minerals. Recent studies show that long-term mineral-associated matter is mostly microbial debris, and its fraction out of soil organic carbon varies by soil type. Hence, viruses that break microbial host cells create microbial debris and contribute to carbon sequestration in soil, yet are missing from carbon flux models. We lack fundamental information about the physiology of soil viruses to link viral lysis of microbes and soil carbon sequestration. Recently, we provided the first estimate of microbial mortality by viruses during soil re-wetting after the dry season, a peak time of carbon flux. Our study estimated mortality of up to 46% of cells within a week. The main knowledge gaps preventing better accuracy of mortality estimates are the average number of viruses produced per host cell and infection rates year-round. I propose to address these gaps using a combination of classic microbiology and cutting-edge bioinformatics. This project will: (1) generate physiological constraints for soil viral mortality across soil types with different amounts of microbial debris, and (2) establish a multi-year monthly time-series of viral infection dynamics of soil microorganisms. I will focus on soil viruses infecting Actinobacteriota, an abundant phylum of drought-resilient soil bacteria that experiences consistently high viral infection rates. A time-series of viral activity will place the culture-based physiological parameters within the context of spatiotemporal dynamics of the entire viral community. This project will create an unprecedented ability to estimate the potential contribution of viruses to soil carbon sequestration and incorporate it into global carbon flux models.

Mots-clés : soil viruses,microbial physiology,carbon sequestration,phage
Projet ERC : scEpiTarget (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Université d'Aarhus — Pays : Danemark — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1810745.0 €

Although all cells of an organism share the same genetic information, they selectively access this information in a cell type- and context-dependent manner. Epigenetic mechanisms, such as post-translational histone modifications (PTHMs) have been identified as central regulators of Transcription Factor-DNA interactions. During cell differentiation, the distribution of PTHMs is modulated to enable the new cell state. Most of the protein complexes that position (writer) and remove (eraser) PTHMs have been identified, but we still do not understand how these proteins are recruited to the genome and thereby dictate the specific genomic distribution of PTHMs. Previous studies were unable to identify these targeting factors as they only interact with a fraction of writer complexes at a time and likely form transient interactions. Thus, new experimental approaches are needed to identify these proteins that are directing localised epigenetic changes. In scEpiTarget I will develop novel single-cell methods to identify the key factors that determine cell-type specific PTHM deposition. I will use the identified regulators to re-target PTHMs and evaluate their impact on cell fate decisions in state-of-the-art cell differentiation systems. Recently, I made a technological breakthrough by developing a method that allows the simultaneous measurement of histone modifications and total RNA in single cells. Together with my background in genetic screening and chromatin biology, this will enable me to reach scEpiTarget’s objectives. The proposed techniques are transferable to study any protein:DNA interaction, making them highly valuable for the research community. Epigenetic pathways are essential for multi-cellular life from the beginning of embryonic development, until their mis-regulation during ageing. The identification of factors regulating PTHM distribution will lead to a better understanding of their function and how they can be therapeutically influenced during pathogenes

Mots-clés : functional single cell multi omics
Projet ERC : SYNDAM (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Université d'Aarhus — Pays : Danemark — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499915.0 €

SYNDAM investigates how the brain detects and clears damaged proteins at the primary loci for information transfer and storage— synapses.  The synapse expresses many proteins that are mutated or dysregulated in major brain disorders. The information transfer rate at synapses is high and, as a result, synapses are continuously exposed to oxidative challenges that arise from local mitochondrial respiration and oxidase activity. This puts synaptic proteins at risk. This risk is exacerbated by the long lifetimes of neuronal proteins, which prolong their exposure to environmental assaults. It is unclear how this apparent risk is mitigated by protein quality control at synapses— a vital process for brain waste clearance and synaptic homeostasis e.g. during sleep. In this context, we face a fundamental knowledge gap: we do not even know which synaptic proteins are targets of oxidative damage, let alone how such damage may trigger protein clearance via key cellular degradation signals such as ubiquitin. This elusive damage-control mechanism is critical for the restorative function of sleep.  To address these knowledge gaps, SYNDAM will (1) identify the synaptic ubiquitin regulators that can detect protein oxidative damage (2) visualize the activity-dependent synaptic protein oxidative damage and ubiquitylation in situ (3) investigate sleep-regulated detection and clearance of protein oxidative damage through ubiquitin  To achieve these goals, we will combine subcellular oxidized and ubiquitylated proteomics, DNA PAINT-based single-molecule localization, chemogenetic induction of synaptic oxidative damage, in situ detection of protein modifications, functional imaging, synaptic activity manipulations, electrophysiology, and sleep behaviour in mice.  SYNDAM will elucidate a critical surveillance mechanism for removing damaged proteins before protein toxicity activates cellular stress responses that may lead to neuroinflammation and degeneration.

Mots-clés : protein quality control,ubiquitin,proteostasis,synapse
Projet ERC : HSC-CRISPR (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
Entité participante : Université d'Aarhus — Pays : Danemark — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499923.0 €

Hematopoietic stem cells (HSCs) reside in the bone marrow where they throughout life sustain continuous blood production through a controlled balance of differentiation and self-renewal. Transplantation of HSCs from a healthy person can replace a defective hematopoietic system of a patient thereby curing the patient for life. HSCs have found increasing therapeutic application, e.g. in hematologic malignancies and hematopoietic genetic disorders. This applies not only to the allogeneic transplantation setting but also to the autologous setting where advances in genetic engineering technologies have enabled autologous gene therapies. However, major challenges remain in both settings pertaining to the scarcity of HSCs, as well as the cells being partially refractory to precise gene correction.  In this research proposal, I will address these challenges by leveraging the unique power of repurposed CRISPR/Cas systems for precise transcriptional manipulation of HSCs. In these systems, the normal DNA-cleaving ability of the Cas9 enzyme is disabled (dCas9) while transcriptional activators or inhibitors are fused to dCas9. By targeting the dCas9-effector proteins to transcriptional start site regions by sgRNA programming, gene transcription can be activated (CRISPRa) or inhibited (CRISPRi). Complex transcriptional engineering is readily achieved using multiple sgRNAs and orthogonal CRISPR systems for simultaneous CRISPRa and CRISPRi.  I will apply these technologies to investigate and enhance therapeutically relevant HSC pathways, namely homologous recombination for precise gene editing, self-renewal, and bone marrow homing. These biological phenomena have previously been studied with techniques that do not have the same elegant properties and therapeutic relevance as CRISPRa/i. With this new state-of-the-art method for precisely controlling gene expression, I will study and manipulate genetic pathways to overcome long-standing challenges in HSC therapies.

Mots-clés : crispra crispri crispr hspcs cd34 stem cells
Projet ERC : TITAN (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed Matter Physics
Entité participante : Université de Jyväskylä — Pays : Finlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1976126.0 €

Designer materials are a key research subject in condensed matter physics offering great opportunities to explore emerging new physics and provide pathways to many-body quantum phenomena that are exceedingly difficult to find intrinsically in isolated materials. The key challenge is to retain the individual quantum ground states in the different components in hybrid materials, while simultaneously tuning the strength of the interactions between them. This requires careful nanofabrication and the complexity of such systems makes further progress difficult. In this proposal, I will use vertical heterostructures of van der Waals (vdW) materials as a flexible platform to engineer elusive quantum states of matter. The general goal of this proposal is the experimental realization of two-dimensional (2D) topological superconductors in vdW heterostructures, and to study the resulting emergent phases of matter. Subsequently, I will use external stimuli (magnetic field, temperature, and chemistry, external gate) to manipulate them. I will couple moir? physics with topological superconductivity and show how the moir? is an external factor that allows additional control over the topologically superconducting phase. Finally, I will combine 2D topological superconductors with ferroelectric materials to fabricate nanoscale reprogrammable topological circuits This will allow controlling topological superconductivity via locally applied electric fields in the heterostructure. I will use molecular beam epitaxy (MBE) to fabricate high-quality 2D vdW heterostructures and probe the properties of the resulting emergent phases using low-temperature scanning tunneling microscopy (LT-STM) and spectroscopy (STS). The combination of MBE-STM in ultra-high vacuum (UHV) allows me to fabricate extremely clean, atomically well-defined, chemically tunable heterostructures and gives me unprecedented access to their atomic-scale structure and electronic properties.

Mots-clés : topological superconductor,majorana zero mode,scanning tunneling microscopy,local density of states,two dimensional heterostructure,two dimensional ferromagnet,moir superlattice,quantum materials
Projet ERC : HYQAP (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental Constituents of Matter
Entité participante : Université technique de Vienne — Pays : Autriche — Rôle : PI
Acronyme de l'entité : TU Wien
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499116.0 €

Generating non-Gaussian quantum states of motion of an optically trapped silica nanoparticle has been a long-standing goal in levitated optomechanics. The main challenge is that its oscillation amplitude in the quantum ground state is orders of magnitude smaller than any pertinent nonlinear optical potential. Conversely, the wave packet size of an optically trapped neutral atom in its ground state is comparable to the laser wavelength, making it straightforward to prepare macroscopic superposition states through state-dependent forces.  This project aims to generate collective quantum states of the motion of a single neutral Cesium atom and a silica nanoparticle. The intrinsic interface provided by the optically mediated interactions offers a feasible route for realizing genuine non-classical states in the nanoparticle’s center-of-mass degree of freedom. My research will focus on three objectives: (i) creating hybrid tweezer arrays of atoms and nanoparticles, (ii) interfacing them through light-induced dipole-dipole interaction, and (iii) leveraging this coupling to entangle the atom and particle motion. Altogether, this will enable the transfer of non-Gaussian states of motion from the atom to the particle, with potential applications for genuine quantum-enhanced sensing and the measurement of Casimir forces and blackbody radiation.  The Hybrid Quantum Atom-Particle (HYQAP) platform becomes possible through a unique synergy of novel methods from quantum optomechanics and atomic physics. Specifically, a high-finesse optical bowtie cavity that enables quantum coherent control will be integrated with tweezer arrays created by acousto-optical deflectors for arbitrary dynamic shaping of traps and interactions, while the single-site imaging will allow us to read out the collective states. These methods have been demonstrated independently for atoms and silica particles, rendering this the ideal moment to bring them together into a hybrid quantum system.