Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MESO_AG (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Université hébraïque de Jérusalem — Pays : Israël — Rôle : PI
Acronyme de l'entité : HUJI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

The brain is responsible for cognition, broadly defined as thinking, by combining mental processes such as sensory integration, perception, and working memory. One of neuroscience’s major challenges is understanding how the brain encodes cognition as a whole. The biggest obstacle to this goal is the complex nature of the brain, which contains billions of entangled neurons that form a dynamic, ever-changing network. We propose to use the mouse model to study cognitive processing streams across the brain. By applying a zoom-out/zoom-in approach, we first study cognition at the mesoscale level (i.e., the population level across many areas) and then zoom in and dissect a specific sub-population. Importantly, we focus on the dynamic brain-wide networks of different cognitive functions that are modulated within single trials and in each individual mouse. We hypothesize that cognitive functions are encoded at the mesoscale level in which information flexibly flows across many brain areas, but with certain motifs and rules. Each objective targets one processing stream and one cognitive function: streams within one cortical hemisphere during sensory integration, streams across cortical hemispheres transferring working memory, and streams between cortex and sub-cortex during perception. In each work package, we will train mice in cognitive behavioral paradigms, and perform a zoom-out/zoom-in protocol with the same mouse. First, we will implement a mesoscale approach (e.g., wide-field imaging and/or multi-fiber photometry) to outline the processing stream within the cognitive network. Second, we will zoom in to dissect a specific node or edge using multi-area two-photon microscopy, labeling techniques, and optogenetics. Importantly, these work packages are modulatory and with substantial overlaps, enabling us to obtain a brain-wide cognitive map that will aid in understanding cognition as a whole in both the healthy and the diseased brain.

Mots-clés : wide field imaging in mice mouse whisker system working memory perception sensory integration cortical large scale dynamics
Projet ERC : GroupHype (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Université hébraïque de Jérusalem — Pays : Israël — Rôle : PI
Acronyme de l'entité : HUJI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1470625.0 €

This proposal concerns enhancing our understanding of linear algebraic group via methods from Boolean function analysis. In particular, it is focused on addressing Thompson's conjecture about conjugacy classes, a longstanding problem in group theory that has captivated researchers for over four decades. We bring together insights from diverse disciplines, weaving together concrete conjectures concerning character value bounds, the independence number of normal Cayley graphs, and most critically, the novel concept of hypercontractivity in groups to provide a framework for a solution to the conjecture.

Mots-clés : discrete analysis over simple groups
Projet ERC : DynamiConsciousness (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : Université hébraïque de Jérusalem — Pays : Israël — Rôle : PI
Acronyme de l'entité : HUJI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1721250.0 €

The unconscious brain’s ability to detect and identify stimuli is essential for our and our loved ones’ survival. For example, recognizing the smell of a fire or our baby's cry. What determines if and how the unconscious brain processes and reacts to information from the environment? As consciousness level diminishes (e.g., during sleep or following brain injury), slow wave activity (SWA) increases, weakening the input-output relationship and increasing response variability. Surprisingly, no study to date has adopted a variability-based approach to responsiveness, seeking common principles that persist across the spectrum of consciousness in both health and disease.  DynamiConsciousness introduces a novel principled framework positing that SWA regionality (i.e., topography across regions) governs responsiveness variability across natural and pathological unconsciousness. I hypothesize that (1) SWA regionality nonlinearly modulates stimulus-induced intra-individual variability (IIV), exhibiting an inverted U-shape relationship, (2) Brain network dynamics is shaped by SWA and govern IIV in a modality-dependent manner, and (3) that IIV can predict consciousness recovery dynamics at the individual level. These hypotheses will be tested through multimodal experiments tailored for altered states of consciousness and by quantifying variability across modalities and time scales in healthy participants (sleep studies) and disorders of consciousness patients (longitudinal study). This interdisciplinary project, combining electrophysiology, neuroimaging, and physiology, offers a new unified framework for understanding responsiveness across the consciousness spectrum by linking within-person variability and SWA regionality. This approach will provide a unique lens for understanding brain functionality and promote a paradigm shift in the way we conceptualize and study consciousness.

Mots-clés : sleep disorders of consciousness slow waves olfaction variability eeg fmri respiration
Projet ERC : iMOTIONS (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Hôpital universitaire de la Charité de Berlin — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : Charité
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499816.0 €

Intestinal fibrosis is a common and serious complication of inflammatory bowel disease (IBD). While intestinal inflammation can be treated pharmacologically based on our current understanding of the underlying pathogenesis, little is known about the mechanisms driving fibrogenesis. Thus no approved therapies exist for intestinal fibrosis. While stromal cells lie at the heart of fibrogenesis, our knowledge of how immune-derived signals instruct aberrant tissue repair and fibrosis is limited. We recently highlighted that the immune-stromal cell axis is a crucial component of IBD pathogenesis. Our research discovered that the IL-6 family cytokine oncostatin-M (OSM) plays a central role in immune-stromal crosstalk in human IBD, and drives pro-inflammatory responses in patients with refractory disease. Genetic deletion of OSM significantly reduced acute intestinal inflammation. Furthermore, our current findings suggest that OSM is required for intestinal remodeling and the regulation of collagen homeostasis by controlling immune cell recruitment. Thus, the OSM-OSMR axis serves as a rheostat for tissue inflammation and repair. We will investigate how OSM modulates intestinal fibrosis and identify upstream and downstream signaling events controlling intestinal fibrosis. I will use (i) newly generated reporter and conditional knock-out mice, (ii) contemporary mouse models of intestinal inflammation and fibrosis, (iii) primary human tissue samples from carefully clinically annotated IBD patients with intestinal fibrosis, and (iv) cutting-edge technologies including single-cell sequencing and imaging mass cytometry to dissect the crosstalk between the immune system and stromal cells driving intestinal fibrosis. This project will deepen our understanding of the intestinal aberrant tissue repair mechanisms acting in IBD and other fibrotic diseases, define novel biomarkers to identify patients at risk of fibrosis and provide the means to prevent and treat fibrotic disease.

Mots-clés : intestinal inflammation,mucosal immunology,fibrosis,stromal cells,immune cells,cytokines
Projet ERC : InteractOmics (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Hôpital universitaire de la Charité de Berlin — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : Charité
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499596.0 €

Cellular interactions are of fundamental importance in life, orchestrating organismal development, tissue homeostasis and immunity. In the immune system, cell-cell interactions act as central hubs for information processing and decision making that collectively determine the outcome of complex immune responses. In leukemias, a cancer originating from immature immune cells, a multilayered network of cellular interactions between immune and leukemic cells underlies effective immune control of the cancer, immune evasion and response to immunotherapies. However, technical limitations in studying cell-cell interactions restrict our understanding into these highly complex and dynamic processes. In order to overcome this limitation, I propose to develop a novel ‘interact-omics’ approach, capable of characterizing millions of cellular interactions across complex organ systems, entire organisms and patient cohorts. Applying the ‘interact-omics’ approach to sophisticated leukemia mouse models will enable us to dissect the dynamic cellular interaction networks between antigen-specific T cells, bystander immune cells and leukemic cells that drive anti-leukemia immunity and immune evasion. In combination with the in vivo perturbation of cellular interactions, this will allow us to systematically decode the cellular logic of how the complex leukemia-immune interplay determines the disease course. Additionally, by making use of leukemia patient cohorts which are either responsive or non-responsive to immunotherapy treatment, we will unravel previously unknown therapy resistance mechanisms and predict therapy response. Together, our approach will set the basis for a comprehensive understanding of the leukemia-immune cell crosstalk underlying immune control, immune escape and therapy response, and may serve as a blueprint to fundamentally expand our insights into other biological processes driven by cellular interactions.

Mots-clés : single cell technologies,leukemia,cellular interactions
Projet ERC : TRACE-it (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and Processes Engineering
Entité participante : Université d'Orléans — Pays : France — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1361010.0 €

Many engineering applications foreseen the usage of small particles for groundwater remediation or for sealing damaged geological confinement barriers, however, delivering materials to a contaminated or damaged region is challenging. TRACE-it aims at controlling the flow of colloidal particles in subsurface geological environments using in situ solute concentration gradients. The phenomenon, known as diffusiophoresis, has a tremendous potential to move colloids to regions that are inaccessible by conventional transport. Diffusiophoretic transport in porous media, however, has received very little attention so far, especially in standard transport in porous media models where it remains unconsidered. What is the magnitude and location of solute concentration gradients produced during subsurface processes? How to use these gradients to transport colloids towards target regions? The answers will be found through a combined experimental-modelling approach to: (i) measure coupled hydro-electro-chemical dynamics, (ii) characterize concentration gradients generated in situ in geological porous media, (iii) identify the influence of concentration gradients on particle transport and develop a macroscale model of transport in porous media that includes diffusiophoresis. TRACE-it integrates the usage of microfluidic experiments, observation techniques, and multi-scale computational fluid dynamics to describe the transport mechanisms at the pore-scale before upscaling to the continuum-scale. The experimental-modelling toolset will open new ways for moving colloidal particles by sensing chemical gradients generated naturally or from human activity, leading them to their target such as oil, contaminants, or reacting minerals. During column-scale experiments, controlling colloid transport will be achieved through the characterization of solute concentration gradients and the use of specifically designed particles.

Mots-clés : porous media microfluidics colloid pore scale hydro electro chemical coupling
Projet ERC : GIGA (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
Entité participante : Nederlandse organisatie voor wetenschappelijk onderzoek — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : NWO
Type d'entité : Recherche
Financement ERC de l'entité : 1421187.5 €

When galaxies merge, do their central supermassive black holes also merge? How does the merger affect star formation and the evolution of galaxies? How does physics beyond the Standard Model of particles affect the Universe? The detection and characterisation of low-frequency gravitational waves (GWs) will address these fundamental and longstanding questions of astronomy and cosmology. Supermassive black holes at the centres of merging galaxies are expected to form binary systems whose orbital motion generates GWs. A cosmological population of such systems combine to build up a GW background (GWB). Such a GWB is also expected if the Universe went through an inflationary period, providing a GW map just moments after the Big Bang. Pulsar timing arrays (PTAs), which are ensembles of extremely stable millisecond pulsars (rotating neutron stars), can be used to study this GWB. Searches for the GWB have typically used sensitive radio telescopes. However, radio data exhibit complex noise processes, predominantly arising from the interstellar medium (ISM), that limit its sensitivity and introduce bias. Gamma rays are immune to the effects of the ISM and a gamma-ray PTA can overcome several of the limitations affecting radio data. GIGA will (a) establish a gamma-ray PTA and independently detect the GWB, (b) develop advanced inference techniques to distinguish its astrophysical origins, (c) measure properties of the ISM through multiwavelength studies, and (d) explore energy-dependent couplings of dark matter. Through these avenues, GIGA will also maximise the sensitivity of radio PTAs and provide crucial validation of their measurements.  The detection of the GWB will provide the first stringent constraints on the dynamical evolution of supermassive black holes and their host galaxies while advanced inferences techniques will aid in disentangling weaker astrophysical sources including cosmic strings and phase transitions, thus probing physics beyond the Standard Model.

Mots-clés : pulsar timing arrays,pulsars
Projet ERC : IGNITE (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : Institut Ruđer Bošković — Pays : Croatie — Rôle : PI
Acronyme de l'entité : IRB
Type d'entité : Recherche
Financement ERC de l'entité : 1500000.0 €

Global warming will increase the frequency of extreme heat events, exemplified by this year’s European heatwave. These thermal extremes pose challenges to insects, who play an indispensable role in terrestrial ecosystems, and whose body temperatures rise with habitat temperatures. Given the alarming trend of global insect declines, it is essential to understand their adaptability in the face of rising temperatures. IGNITE aims to answer one of the most urgent questions in ecology today—Will insects be able to survive the upcoming heat stress?  To answer this question, we will test insects’ resilience to thermal extremes using an interdisciplinary approach that integrates insect physiological and behavioral responses with relevant micro- and macro-climates. Using state-of-the-art 3D thermal imaging of the habitat, we will determine how microclimatic heterogeneity combined with insect behavioral thermoregulation governs insect survival to extreme heat. While such microclimatic insights are pivotal, predicting long-term changes requires a macroclimatic perspective. Thus, we will develop a high-resolution climatic model of surface temperatures to forecast heatwave frequency and intensity on Mediterranean islands. We will test insects’ thermal plasticity potential with novel reciprocal transplant experiments in both the field and laboratory. We will use ants as model insects, due to their global distribution and ecological importance. Under temperature extremes projected by the macroclimatic model, we will determine ant thermal plasticity and its ramifications on ecosystem functions such as seed dispersal, plant productivity, and biodiversity.  IGNITE integrates findings from climatology, behavioral ecology, and ecophysiology to understand insect resilience to temperature increases and cascading effects on ecosystems. By doing so it will pioneer global change biology research in the Mediterranean Region using islands as natural laboratories to study global warming.

Mots-clés : microclimate,heat waves,climatic modeling,geophysics,ecophysiology,ecology,behavior,ecosystem functioning
Projet ERC : ONCO-COMP (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Sant Joan de Déu-Barcelona Children’s Hospital — Pays : Espagne — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 387086.1 €

Childhood cancers are believed to be rooted in aberrant development, a notion supported by their (i) generally low mutational burden, (ii) high prevalence of single (often epigenetic) driver events and (iii) occurrence during confined developmental periods. Yet, the exact origins of developmental tumours remain one of the principal enigmas of pediatric oncology. A prime example are malignant rhabdoid tumours (MRTs): they are astoundingly genomically simple but extremely deadly childhood cancers that arise almost exclusively in the first two years of life, and are driven by biallelic inactivation of the SWI/SNF chromatin remodelling complex subunit SMARCB1 (>95% of cases). We still do not know what determines oncogenic competence upon SMARCB1 loss. In particular we wonder: (1) What are the cell(s)-of-origin of rhabdoid tumours and what is their normal differentiation potential? (2) What is the molecular framework that facilitates oncogenic transformation upon SMARCB1 loss? (3) What is the contribution of the niche (local and systemic) to the acquisition of oncogenic competence? And, considering the epigenetic nature of the oncogenic event, (4) is the oncogenic MRT state reversible, and how?  To answer these questions, we will combine state-of-the-art lineage-barcoded single-cell genomics, spatial transcriptomics, single-cell resolution wholemount imaging, CRISPR/Cas9 and epigenomic approaches, as well as integrative computational analyses, using transgenic mouse, induced pluripotent stem cell and patient-derived xenograft rhabdoid tumour models.  This project will provide fundamental insights into the cell autonomous and non-autonomous determinants of oncogenic competence upon SMARCB1 loss. Based on our findings we hope to unlock targeted treatments for MRT patients. Importantly, the conceptual and experimental framework we establish will open up new investigative opportunities for a multitude of developmental cancers.

Mots-clés : oncogenic competence,epigenomics,rhabdoid tumours,chromatin,lineage tracing,developmental tumours,prime editing,cell of origin,tumour initiation
Projet ERC : PROTEOFORMER (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Université Masaryk — Pays : Rép. Tchèque — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1810000.0 €

The human body can synthesize ~70’000 different proteins. These proteins diversify into millions of proteoforms, e.g., by associating into complexes or acquiring functionalities called post-translational modifications (PTMs). Distinct proteoforms are often found in different cell types and have diverse functions. Dysregulation of specific proteoforms is associated with many diseases, including neurodegeneration or cancers, highlighting the need for their study and modulation. Despite these needs, most drug-like molecules are designed to indiscriminately activate, inhibit, or destroy a target protein—they are blind to the localization or function of different proteoforms. PROTEOFORMER goes beyond the protein by developing chemical tools for manipulating specific protein forms. In two parallel initiatives, PROTEOFORMER will: (1) Target a specific proteoform of the muscarinic acetylcholine receptor—relevant to Parkinson’s disease treatment—dissecting its function and laying the groundwork for new therapies. (2) Modify post-translational modifications of matrix metalloproteinase-2—a key regulator of neuroinflammation—aiming to unravel their so-far-elusive function. PROTEOFORMER offers tailored reagents that (i) recognize the protein target, (ii) bring a reactive group to the target’s surface, and (iii) attach molecular cargo to the protein via a proximity-induced reaction. It rethinks this ‘ligand-directed chemistry’ by introducing functional, proteoform-manipulating cargo: (1) A blocker of a partner protein, enabling proteoform-selective inhibition within a cell-specific complex. (2) A post-translational modification or its eraser, enabling on-demand switching between proteoforms with newly developed proximity-driven chemical reactions. PROTEOFORMER develops new chemistry for manipulating proteoforms beyond current capabilities. These general concepts represent a chemical solution to long-standing challenges in biology that are intractable with traditional methods.

Mots-clés : proximity driven protein labeling,post translational modifications,chemical neuroscience