Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MAGMA (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Université de Caen Normandie — Pays : France — Rôle : PI
Acronyme de l'entité : UNICAEN
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1970480.0 €

Tertiary lymphoid structures (TLS) are ectopic lymphoid tissues that drive immune responses at sites of chronic inflammation. They are of widespread interest in biology and medicine since their presence dramatically influences disease course in autoimmune disorders, infection, and cancer. However, due to their small size and their development in chronically altered tissues, TLS cannot be selectively targeted or detected by imaging. The current project aims at developing new methods to map and eventually destroy the TLS in a non-invasive manner. To this aim, a new formulation of injectable superparamagnetic particles will be produced and targeted to the TLS. A set of innovations in contrast agent design and material chemistry will be developed to dramatically increase targeting efficiency compared to existing methods. By combining these innovations, intravenously injected superparamagnetic particles will accumulate in TLS in large numbers, thereby allowing their non-invasive detection by clinically available imaging modalities (magnetic resonance imaging) and emerging technologies (magnetic particle imaging). This will also open the possibility of thermal destruction of TLS using magnetic hyperthermia, providing a way to suppress a local immune response without affecting systemic immunity. The scientific advances and technologies of the MAGMA project will have clinically relevant applications, such as diagnosis of chronic inflammation, selection of patients for treatment with immune checkpoint inhibitors in cancer and spatially selective suppression of immunity in autoimmune diseases.

Mots-clés : tertiary lymphoid organs,magnetic resonance imaging,magnetic particle imaging
Projet ERC : DecodeNP (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : German Center for Neurodegenerative Diseases — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : DZNE
Type d'entité : Recherche
Financement ERC de l'entité : 1999621.0 €

Adaptive behaviour to ever-changing environments is crucial for an animal’s survival in conditions of immediate threat. Meanwhile, there is growing evidence that psychiatric conditions, including anxiety disorders, are at least partly based on maladaptive learning. Neuropeptide signalling plays a key role in regulating synaptic plasticity and hence learning in a state-dependent manner, and dysregulated peptide signalling has been observed in patients suffering from psychiatric disorders. Due to specific expression of peptides and their receptors in distinct cell types and microcircuits, they can contribute to the specificity of neural communication on both temporal and spatial scales. However, the signalling mechanisms and behavioural roles of neuropeptides in individual circuit elements are not well understood. In this proposal, we will use a multimodal approach to determine the role of neuropeptides in innate and learned fear and anxiety states. We will focus on microcircuits of the amygdala, more specifically on distinct interneuron types, which co-release different peptides with their common main transmitter GABA. Using state-of-the-art technology, we will analyse under which conditions neuropeptides are released from interneurons, and probe their causal contribution to fear learning and anxiety states with intersectional genetic interrogations. Large-scale, longitudinal in vivo calcium imaging combined with novel spatial transcriptomics will further reveal peptide impact on circuit computations. As both amygdala circuitry and function as well as neuropeptide expression are evolutionarily conserved, we expect that this proposal will unravel fundamental mechanisms of neural circuit functions for survival. This research will not only provide novel insights into the neural mechanisms of fear and anxiety, but will also hold significant clinical relevance for understanding the underlying pathophysiological processes that contribute to psychiatric disorders.
Projet ERC : EnergizeTau (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : German Center for Neurodegenerative Diseases — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : DZNE
Type d'entité : Recherche
Financement ERC de l'entité : 2194940.0 €

The intraneuronal somatodendritic "missorting" and aggregation of Tau are pathological hallmarks in neurodegenerative diseases (NDDs) like and Alzheimer's disease (AD), and are thought to be drivers of neurotoxicity. That NDDs manifesting with Tau "missorting" present with (neuro)metabolic abnormalities, often prior to pathology onset, is largely overlooked. EnergizeTau investigates the ground-breaking new idea that the somatodendritic re-sorting of Tau is a physiological response to bioenergetic challenges faced by excitatory neurons, such as hyperexcitation or energy deprivation. In its proposed role as modulator of neuronal energy management, Tau modulates the cellular energy demand through molecular interactions with key cellular functions, e.g., synaptic activity, ATP production and protein translation, and alters the neuronal metabolism. Continued energetic stress in disease results in irreversible "silencing" and Tau aggregation in affected neurons. Using my uniquely broad Tau expertise, we decipher how Tau interferes with energy demanding cellular functions to modulate neuronal energy household downstream of bioenergetic stress. Light-induced Tau expression and CRISPR-edited human neurons enable to study Tau's molecular actions by interactomics and single-molecule imaging, and the effects on cellular functions. Tau's influence on the neuronal metabolism is determined by longitudinal live cell metabolite imaging and spatial transcriptomics in human brains, and the impact on gene and chromatin regulation by Cut&Tag and DNA-FISH. Whether stressors converge on energy limitation as a driver of Tau re-sorting is assessed by high-content metabolite imaging. EnergizeTau introduces the metabolic component of Tau (patho)biology and generates a paradigm shift in NDD research. It creates space for re-thinking hallmark protein pathology in NDDs, and has the potential to result in new approaches targeting the neuronal energy metabolism to prevent and treat NDDs.

Mots-clés : alzheimer s disease,tauopathies,tau,protein interactions,metabolism
Projet ERC : PowerMiT (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Université Eberhard Karl de Tübingen — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999819.0 €

T cell therapy with chimeric antigen receptor (CAR)-T cells is a curative-intent, transformative treatment aimed to boost antitumor abilities of host T cells against refractory/relapsed B cell malignancies and, recently, against refractory/relapsed myeloma. Major challenges of current CAR-T cell immunotherapies are the loss of long-term efficacy, the occurrence of toxicities including infections, and a lack of personalized patient strategies including biomarkers for response prediction and interventions to enhance CAR-T cell efficacy. This proposal builds on our first evidence for a major role of the gut microbiome in CAR-T cell therapy, and addresses these challenges by presenting a translational research strategy aimed to dissect and leverage the impact of gut microbes in its antitumor efficacy. In Aim 1, we will investigate the hypothesis that gut and intratumoral microbiome configurations and its metabolites are associated with clinical response of CD19-CAR-T cells in lymphoma, with immunophenotypes of these engineered T cells and the tumor immune microenvironment. We will examine the effects of nutrition and antimicrobial drugs on microbiome features to identify potential mechanisms and therapeutic levers. In Aim 2, we will address the biology of microbiome-CAR-T cell interactions through experimental gut microbiome modulations, and humanizing mice with patient-derived microbial ecologies and individual species and strains in preclinical research models. In Aim 3, we will assess potential therapeutic interventions to increase CAR-T efficacy by investigating the action of microbiome-derived metabolites on CAR-T cells and studying phage- and diet-based interventions to mitigate antibiotic-induced gut microbiome dysbiosis. Characterising the function of the microbiome and its products in CAR-T immunotherapy harbours an enormous potential to improve current and future T cell transfer therapies for numerous patients suffering from cancer.

Mots-clés : car t cell therapy hematologic malignancy metabolome gnotobiotics
Projet ERC : GBM_Cellular_States (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : The general hospital corporation — Pays : Etats-Unis — Rôle : Partner
Type d'entité : Autres
Financement ERC de l'entité : 37500.0 €

Cellular heterogeneity is a fundamental property of glioblastoma (GBM) tumors and presents a major barrier for therapeutics. During the past six years we characterized this heterogeneity in glioblastoma, and in other types of glioma, using single cell RNA-seq (scRNA-seq). We found consistent patterns of heterogeneity across patients, such that each tumor harbors multiple subpopulations of cells that resemble neurodevelopmental cell types. The consistency of these cellular states across patients highlights their potential clinical significance. Yet, our understanding of how these common states are regulated and of how distinct states respond, individually or in combinations, to potential treatments, remain poorly understood. Furthermore, it is unclear if additional states of clinical significance remain to be uncovered. To address these challenges, we will perform extensive studies of GBM patient samples, animal models and gliomasphere culture models. First, we will dissect the regulation of the common cellular states (Aim 1). Single cell ATAC-seq of patient samples will be used to infer transcriptional regulators, Spatial Transcriptomics will be used to infer environmental interactions, and resulting predictions will be tested further in established model systems. Second, we will search for novel cellular states, including rare states or those specifically associated with invasion to the brain parenchyma (Aim 2). Third, we will examine strategies for treatment of heterogenous tumors that are composed of multiple states (Aim 3). We will screen for state-specific drug sensitivities, as well as for drugs that induce state transitions, and develop rational combinations to eliminate multiple co-existing states, while considering interactions among states. Taken together, these studies will considerably expand our understanding of cancer heterogeneity and develop strategies to target heterogeneous tumors.

Mots-clés : glioma single cell rna seq
Projet ERC : ESTER (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Study of the Human Past
Entité participante : Université Christian Albrecht de Kiel — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1981430.0 €

Understanding population trends over the past 12,000 years is crucial for unraveling the complexities of social development. Population size influences social structures, exchange systems, environmental interactions, cultural transmission, and societal resilience. Current global population figures, derived since the 1970s, are educated guesses based on limited data and deductive methods, hindering accurate prehistoric assessments. Regional studies, emerging data sources, and innovative methods offer new possibilities, exemplified by the XRONOS database, a significant contribution from our research group. The ESTER project proposes a groundbreaking approach, employing hierarchical Bayesian modeling and data assimilation techniques to integrate heterogeneous big data into population development models. This method evaluates data reliability, compensates for missing information, and facilitates regionalized estimates balancing varying data availability. Focused on Europe and Western Asia from 12,000 to 2,000 BP, the project aims to provide the first big-data-based regionalized population estimate. Sub-projects investigate climatic shifts, societal collapses, and the impact of innovations like agriculture on population dynamics. The project aligns with Ester Boserup's theories, reflecting her positive vision of humanity capable of change. The ESTER project introduces a novel methodology, offering valid bases for investigating cultural and social configurations dependent on population numbers. It provides confidence intervals, 50-year temporal resolution, and absolute population numbers. These results can test causal relationships with climatic changes and volcanic eruptions. Beyond archaeology, they offer indicators for human impact and land use, aiding various palaeosciences in investigating human-environment relationships with unprecedented quality and reliability, fostering awareness of our past and its connection to ongoing global change.

Mots-clés : computational archaeology,population estimates,prehistoric archaeology,human impact,bayesian hierarchical modeling
Projet ERC : UltraSpecT (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed Matter Physics
Entité participante : Université Christian Albrecht de Kiel — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Based on my groundbreaking advancements in realizing internal radiation sources inside electron microscopes, generating ultrashort and coherent electromagnetic radiations in interaction with electron beams, I propose to develop a platform for ultrafast and phase-locked electron-beam spectroscopy of solid-state-based quantum networks, beyond the dephasing time T2. My platform relies on the following key elements: (i) shaping electron wavepackets with light, (ii) implementing three-dimensional electron-driven photon sources, and (iii) employing correlative measurements to unravel the quantum statistics of photons evolving in solid-state-based photonic systems and quantum networks. This scenario enables an outstanding temporal resolution and an unprecedented degree of mutual coherence between the radiation sources and the near-field of the electron wavepacket itself. By combining these capabilities, I aim to map the excitation/emission paths, quasi-particle interactions, charge and energy transfer dynamics, as well as quantum jump and revival processes at the attosecond timescale and nanometer spatial resolution. UltraSpecT opens new horizons in quantum-sensitive measurements, leveraging novel technological advancements in electron microscopes to explore the frontiers of quantum science. It aims to investigate decoherence dynamics beyond T2 using electron microscopes, enabling the exploration and manipulation of photon dynamics in individual single-photon emitters coupled to or embedded in quantum networks. UltraSpecT's ambitious goals span a highly interdisciplinary field, combining quantum optics with electron microscopy. My team and I will address the ambitious aspects of UltraSpecT by applying our extensive knowledge in both theoretical and experimental aspects of electron – light – matter interactions. I will further implement a risk mitigation plan that includes employing a variety of methods to realize our required radiation sources and beam shaping strategies.

Mots-clés : electron photon interactions,cathodoluminescence spectroscopy,decoherence,correlative measurements,nano and quantum optics,single photon emitters,metamaterials,electron driven photon sources
Projet ERC : CONTROL (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
Entité participante : Université de Göteborg — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

A fundamental physical property of A fundamental physical property of matter is its ability to interact with light. This is not only the basis of fascinating concepts like seeing colours, but also the foundation of life and advanced technologies. Yet, some basic physical laws hamper possible utilisations. It is therefore of great importance to examine how to bend these laws, how to bypass them and by so doing open up new opportunities for novel applications. This is exactly what this project aims to do.  Plant leaves are green because they absorb visible light. However, it is less known that this light-matter interaction can be enhanced to the point where it is so strong that the photon and molecule cannot be regarded as separate entities, but as a combined system with unique properties. Nature uses strong pigment-pigment interactions to rapidly funnel absorbed sunlight to the photosynthetic reaction centre. However, up to now, organic solar cells do not take advantage of such quantum processes to enhance light to electricity conversion.  In CONTROL, I will use a chemical viewpoint to develop unique molecules optimised for strong light-matter interactions, and with these examine excited state processes of strongly coupled systems. My aim is to funnel excitation energy to charge transfer states in an organic heterojunction using the delocalised nature of hybrid light-matter states. This interaction enables transport of excitation energy over distances much longer than have been previously considered feasible. Using time-resolved optical spectroscopy and photoconductivity, I will systematically analyse the interaction between delocalised hybrid states and localised charge transfer states, allowing design criteria to be formulated. The outcome of this research program will be the description and mechanistic revelation of a novel quantum physical phenomenon that can enable development of organic solar cells from simple layered structures with unprecedented efficiencies.

Mots-clés : strong coupling
Projet ERC : AUTO-SELECT (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Innovavector srl — Pays : Italie — Rôle : Partner
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 37500.0 €

(Macro)autophagy is an evolutionarily conserved catabolic process induced to preserve cellular homeostasis under conditions of stress, such as nutrient starvation. Upon autophagy activation cellular components are engulfed by autophagic vesicles, which then fuse with lysosomes for substrate degradation. Despite the unquestionable physiological and medical relevance of nutrient- and pharmacological-induction of autophagy in human health, the precise identity of autophagy substrates and the rules governing their selection in vivo are largely unknown. AUTO-SELECT’s goal is to provide a framework to identify physiologically relevant autophagy substrates in different organs and to determine the signaling events that govern their selection. This proposal relies on (1) newly generated mouse models to genetically manipulate autophagy and key autophagy regulators, (2) tools to quantitatively measure autophagy substrate delivery to lysosomes and subsequent degradation in vivo, and (3) -omic technologies and bioinformatic tools to dissect the molecular events that govern substrate selection in response to diverse stimulations in a tissue-specific manner. In addition, AUTO-SELECT will develop new strategies to modulate selective autophagy and test their therapeutic relevance in connective tissue disorders characterized by the intracellular accumulation of misfolded procollagen molecules. AUTO-SELECT has the potential to discover new rules governing cargo selectivity during autophagy and, hence, to provide new links between energy metabolism and cellular quality control that might be exploited for autophagy modulation to treat human diseases.

Mots-clés : autophagy,selective autophagy,lysosome,nutrient sensing,mtor
Projet ERC : EXPAND (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth System Science
Entité participante : National Oceanography Centre — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : NOC
Type d'entité : Recherche
Financement ERC de l'entité : 2254712.6 €

Often called ‘ocean deserts’, subtropical gyres have low biological productivity but, due to their immense size, contribute significantly to carbon sequestration regulating global climate. In gyres, biological productivity strongly depends on nitrogen supplied by microbes called diazotrophs, capable of fixing molecular nitrogen (N2) into bioavailable nitrogen forms. Earth system models predict increasing uncertainty in biological productivity towards the end of the 21st century. Such uncertainty responds to N2 fixation parametrisation in models and is largely driven by the scarce observations available in the Indian Ocean (IO), representing only 1% of the N2 fixation data available globally. Moreover, our current understanding of N2 fixation is mainly based on nutrient availability (phosphorus and iron) impacts on diazotrophs. However, my previous research shows that other controls including ocean circulation and diazotroph/non-diazotroph interactions are key in shaping N2 fixation inputs locally. None of these controls have been comprehensively examined over the vast extension of the IO, nor throughout seasons. We will conduct oceanographic expeditions covering the full extension of the IO gyre at its minimum and maximum expansion seasons. Gyre expansion will be tracked with satellite and in situ hydrographic and current speed measurements. The impact of chemical (nutrients), physical (ocean circulation), and biological (species interactions) controls on N2 fixation will be comprehensively measured, using at-sea experiments and up-to-date isotopic and molecular analyses. Moreover, seasonal variability will be monitored over a full year with mooring lines anchored at the centre, northern and southern edges of the gyre, equipped with DNA samplers and a newly designed automatic device measuring N2 fixation rates. These datasets will link cellular to ecosystem processes, bridging the gap between ocean desert expansion and N2 fixation in the world’s least explored gyre.

Mots-clés : nitrogen fixation subtropical gyres primary productivity climate change