Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : CONNASHION (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Université Vie-Santé Saint-Raphaël — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1741250.0 €

Non-alcoholic steato-hepatitis (NASH) is a major risk factor for hepatocellular carcinoma (HCC), the 6th most common cause of cancer-related death worldwide. The transition among different NASH stages to HCC stems from the complex interaction of multiple factors, including gut-liver axis modifications and a progressive dis-architecture of the liver parenchyma. The central role of endothelial cells in regulating the metabolic crosstalk along the gut-liver axis and in shaping the spatial organization of the liver parenchyma suggests a potential vascular control of NASH progression. However, the possibility to precisely define the endothelial contribution is restrained by the limited ability to correlate gene expression profiling and functional readout, such as protein phosphorylation, with the complex morphological modifications occurring during NASH. To overcome these limitations, we combined innovative “spatial sorting” strategies with transcriptomics and quantitative phosphoproteomics, providing the first draft of the anatomical organization of proteins signaling in the liver vasculature. Moreover, we unambiguously identified tyrosine phosphorylation – the main target of the anti-angiogenic therapy (ATT) – as one of the most spatially regulated signaling event.  Building on this expertise, we will combine spatial sorting strategies in gut and liver with mouse models of NASH progression and advanced imaging modalities to pursue the following aims: 1. Provide a spatiotemporal characterization of the gut and liver vasculature undergoing NASH development. 2. Dissect the vascular determinants of NASH progression. 3. Identify the molecular mechanisms underlying the synergistic effect between AAT and immune checkpoint  inhibition.  Together, our results will lay the foundation for understanding the molecular basis of a synergistic AAT and immune therapy in HCC, and help to identify novel prognostic markers as well as potential therapeutic targets.

Mots-clés : vascular biology,liver zonation,nash,hcc,anti angiogenic therapy,immune therapy
Projet ERC : AUTO-T-NERVES (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Université Vie-Santé Saint-Raphaël — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Guillain-Barré syndrome (GBS) is a rare heterogenous inflammatory peripheral neuropathy usually triggered by a preceding infection and causing a potentially life-threatening progressive muscle weakness. While the disease is generally considered to have an autoimmune basis, the underpinning immune-mediated mechanisms remain mostly elusive. This aspect poses a significant medical challenge in terms of accurate diagnosis, prognosis, and treatment. Building on our recent findings revealing that autoreactive T cell immunity play a key role in a subset of GBS patients, the project proposed herein aims at systematically elucidating its relative contribution to distinct GBS subtypes and disease stages. To this end, we will use cutting-edge technical approaches that enable the study of potentially rare autoreactive T cells in human biological samples (i.e. blood, cerebrospinal fluid and tissue biopsies) through three specific aims: Aim 1 is to perform in-depth immunophenotyping of blood-circulating immune cells for identification of potential variations in their frequency and distribution across GBS subtypes and stages; Aim 2 is to provide a systematic characterization of self-reactive T cells in patients’ biological samples by combining in vitro T cell screenings and ex vivo tetramers staining with high-throughput single cell analysis, such as single T cell clone generation, single cell RNA sequencing and TCR sequencing; Aim 3 is to dissect the cellular and molecular bases of cross-reactive T cell immunity in GBS by integrating in vitro sequential stimulation, single T cell clone generation and TCR sequencing with mass spectrometry-based immunopeptidomics or lipidomics. The outcomes of this project will significantly expand our understanding of the immunopathology of inflammatory peripheral neuropathies and advance our basic knowledge of human autoreactive T cell biology, with substantial implications for biomedical applications.

Mots-clés : autoreactive t cells,group 1 cd1 restricted unconventional t cells,guillain barr syndrome,inflammatory neuropathies,human immunology,cross reactivity
Projet ERC : HEPAGENE (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Université Vie-Santé Saint-Raphaël — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1993750.0 €

In vivo genetic engineering of hepatocytes may represent a definitive cure for monogenic metabolic diseases. Integration of the therapeutic transgene into the target cell genome is essential for long-term expression after a single dose early in life and can be achieved by semi-randomly integrating lentiviral vectors or site-specific genome editing. Maintenance of the genetic modification upon hepatocytes proliferation in liver growth and turnover requires targeting the cells underlying these processes. Little is known about post-natal liver growth and how different hepatocyte subsets contribute to it. Unexpectedly, we found that most hepatocytes are quiescent during liver growth, and a fraction of them generate most of the adult tissue. The overall goal of HEPAGENE is to dissect hepatocyte heterogeneity in post-natal liver maturation and unravel its implications for in vivo gene engineering, to ultimately design and develop safe, effective, and durable gene therapies to treat diseases of hepatic metabolism in pediatric patients. To achieve this goal, we will: i) characterize molecular programs of proliferating and quiescent hepatocyte subsets; ii) assess their susceptibility to lentiviral gene transfer and nuclease-mediated gene editing, in both normal mice and in a disease model of methylmalonic acidemia, a severe early-onset disease, taken as paradigmatic of inherited metabolic diseases; iii) estimate clonal dynamics of genetically modified hepatocytes in vivo in non-human primates and analyze gene signatures in human liver samples, to establish a correspondence between murine and primate’s hepatocyte subsets. We will exploit state-of-the-art organoid, single-cell and multi-omic analyses including latest-generation spatial transcriptomics. HEPAGENE will lead to improved understanding of liver biology and gene engineering of hepatocytes, paving the way for novel genomic medicine products that offer hope to children affected by otherwise incurable metabolic diseases

Mots-clés : lentiviral vectors,gene editing,hepatocytes proliferation,hepatocytes maturation,spatial transcriptomics
Projet ERC : AFRIFOR (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Human Mobility, Environment, and Space
Entité participante : Université norvégienne pour les sciences de la vie — Pays : Norvège — Rôle : PI
Acronyme de l'entité : NMBU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1984243.0 €

The importance of non-timber forest products (NTFPs) for better balancing tropical forest conservation and poverty alleviation goals is increasingly recognised. Yet, in Africa, poor understanding of the impact of harvesting on species’ populations and forest carbon stocks, together with little information on the traditional institutions which have informally regulated NTFPs extraction in the past -and could continue to do so in the future-, hamper the use of NTFPs in both forest conservation and development initiatives. AFRI-FOR will gather the knowledge needed to determine (1) the key enablers of sustainable harvesting for groups of plant or wild meat species, (2) which types of NTFP harvesting can have synergies with carbon storage, and (3) how traditional institutions can be integrated into formal conservation. To achieve these objectives, AFRI-FOR provide new methods, including (i) a new interdisciplinary approach for investigating NTFPs harvesting impacts, combining traditional ecological knowledge (TEK, from local communities), surveys of plants and wildlife, market surveys and modelling techniques; and (ii) a novel standardised protocol for gathering information about traditional institutions and compliance towards them. AFRI-FOR will gather data and knowledge from 20 socio-ecological forest contexts in five countries (Sierra Leone, Cameroon, DR Congo, Uganda and Kenya), which will allow insights to transcend single sites and provide a much-needed general understanding. This high-risk and high-gain project will provide a step-change in our ability to inform forest conservation in Africa, by identifying synergies between biodiversity conservation, carbon storage and poverty alleviation goals.

Mots-clés : tropical forests,conservation,biodiversity,carbon storage,cultural values,poverty alleviation
Projet ERC : FOLOME (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 2000000.0 €

The infiltration of CD8+ T cells in tumors is crucial for the development of immunity against cancer. We have recently identified a tissue-resident macrophage population expressing the folate receptor 2 (FOLR2) and infiltrating human and murine breast tumors. We have shown that tumor-infiltrating CD8+ T cell form lymphoid aggregate around FOLR2+ macrophages in a perivascular niche. The abundance of FOLR2+ macrophages associates with lymphocyte infiltration, the onset of tertiary lymphoid structures (TLS) and favorable prognosis. The abundance of TLS in cancer correlates with better prognosis and clinical response to immunotherapy. Yet, the molecular and cellular cues underlying TLS formation in tumors are ill understood. Here we hypothesize that FOLR2+ macrophages locally shape the compartment of tumor-infiltrating CD8+ T cells. Mechanistically, we will address if FOLR2+ macrophages spark local CD8+ T cell responses directly, by interacting with T lymphocytes or indirectly, by fostering TLS formation. To this end, we will (1) develop a high dimensional analysis of the FOLR2+ macrophage-perivascular niche using tissue imaging, spatial transcriptomic and single-cell RNA sequencing; (2) implement a new murine genetic model developed in the lab enabling the inducible ablation of FOLR2+ macrophages and conditional gene inactivation; (3) deliver a mechanistic analysis of cellular cross-talks involving FOLR2+ macrophages and supporting the development and maintenance of TLS. Lastly, we will explore new immunotherapy strategies harnessing the immunogenic function of FOLR2+ macrophages purposed to induce anti-tumor CD8+ T cell responses. To this end, we will use antibody-mediated targeting of FOLR2+ macrophages to increase antigen presentation and/or innate activation. This study will provide fundamental insights on how tissue-resident macrophages regulate tumor-immunity and a proof of concept for macrophage subset-specific therapeutic interventions to treat cancer.

Mots-clés : macrophages,cd8 t lymphocytes,tertiary lymphoid structures,anti tumor immune response
Projet ERC : MoMacTrajectALI (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Université de Liège — Pays : Belgique — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999863.0 €

The lung is particularly exposed to airborne and blood-borne insults. The mechanisms underlying lung tissue repair are therefore of fundamental biological importance and have critical implications for the prevention life-threatening inflammatory and tissue-damaging responses. Lung-resident tissue macrophages and inflammatory monocyte-derived macrophages (InfMoMac) are key players in the maintenance of homeostasis, repair responses and disease pathogenesis. Yet, to date, the complexity of lung macrophage responses after injury is far from being resolved. Here, we propose to explore InfMoMac trajectories and functional diversity in an unprecedented manner. To this end, we will use mouse models of infectious and non-infectious lung injury combined with single cell and spatial analyses, robust fate-mapping models and gene targeting approaches to investigate the spatio-temporal regulation, the subtissular niches, the intrinsic molecular programs and the extrinsic stress-, inflammation- and niche-related signals imprinting the identities and functions of InfMoMac subpopulations, and the functional consequences of the maintenance of InfMoMac for lung immunity to a subsequent challenge. Finally, we will investigate the interactions of InfMoMac with niche cells in humans by analyzing the InfMoMac landscape in human injured lungs and by studying a novel human embryonic stem cell-derived lung organoid model in co-culture with monocyte-derived cells. Based on robust preliminary data, sophisticated models and cutting-edge technologies, this ambitious project will increase our understanding of the basic mechanisms underlying the fine-tuning of InfMoMac trajectories in response to lung injuries and will thus provide robust foundations to manipulate their fate in medically relevant conditions such as severe respiratory viral infections and acute respiratory distress syndrome.

Mots-clés : macrophage plasticity and function lung damage and repair tissue immunity respiratory viral infection macrophage niche cell interactions epigenetic imprinting in vivo models ex vivo human organoids
Projet ERC : Afropolis Tungul (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Study of the Human Past
Entité participante : Université de Varsovie — Pays : Pologne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999950.0 €

The project aims at writing an urban biography of Tungul (Old Dongola, Sudan). The use of the native Nubian designation of the city underscores its medieval African heritage, while the “biographical” approach aids in conceptualizing the city as a complex, living organism. Tungul was originally the capital of the kingdom of Makuria which transformed into a city-state under the patronage of Funj sultans (16th–19th cent.). Makuria was a medieval African kingdom that thrived in the Middle Nile Valley from the end of the 4th cent. to the late 15th cent. CE. This project is a multidisciplinary attempt at gaining a profound understanding of settlement persistence in riverine Africa and it intends to amass extensive documentation of a medieval and pre-modern city. The biography will be based on analyses of Tungul’s urban design and planning, built structures, material culture, bioarchaeology, as well as micromorphology and geochemistry. The results will significantly contribute to the Nubian datasets and offer new perspectives for broader archaeological and theoretical studies on urbanism and complex societies. The proposed biography will focus on three entangled and mutually inclusive research themes: the capital’s cityscape, its design and planning; the city’s inhabitants; climate and environment. The project intends to venture beyond the traditional narratives, steeped in either ecological or political determinism, to create a balanced narrative devoting equal attention to climatic, environmental, socioeconomic and political factors. The majority of work will focus on the collection and analysis of data on Tungul in the Makurian period (4th–15th centuries). However, the research objectives require combining this material with data for the Funj period (16th–19th centuries), which constitutes an outcome of the ERC Starting Grant UMMA, and with other information obtained through decades of excavations, to consolidate the results of all research conducted at Tungul.

Mots-clés : biography,urbanism,africa,nubia,makuria,funj,sudan
Projet ERC : NewGLASS (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Materials Engineering
Entité participante : Université d'Aalborg — Pays : Danemark — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1996935.0 €

Oxide glasses are one of the most important material families owing to their unique features, such as transparency, tunable properties, and formability. Emerging solutions to major global challenges related to energy, health, and electronics require new scientific breakthroughs in glass chemistry, mechanics, and processing. The realization of these goals is severely restricted by the main drawback of glass, namely high brittleness. Furthermore, new glass compositions are today developed through time-consuming trial-and-error experimentation due to their inherent non-equilibrium nature and disordered structure.  A major task is therefore to initiate a paradigm shift within the field of glass science and technology, going from empirical to model-based approaches for the design of new glass compositions and microstructures with improved fracture resistance. This requires the development of computational approaches, from ab initio calculations to artificial intelligence, to integrate structural descriptors and glass chemistry with advanced processing and mechanical properties into holistic tools.  NewGLASS challenges the current glass design strategies in order to create such tools. For this purpose, an interdisciplinary approach is proposed, in which structural descriptors at the short- and medium-range length scales are first identified and quantified based on emergent statistical mechanics and persistent homology techniques. Guided by these results, high-throughput simulations at various length scales are combined with machine learning algorithms to design novel glass compositions, tailored deformation mechanisms, and 3D-printed microstructures to achieve superior fracture resistance. By having experiments and modelling complement and advance each other reciprocally, NewGLASS will find order in disorder and provide the scientific breakthroughs for the accelerated design of glasses with outstanding mechanical performance, thus opening up for many new applications.

Mots-clés : glasses,mechanical properties,topological data analysis,statistical mechanics,machine learning,molecular dynamics simulations,3d printing
Projet ERC : PROXISENSES (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Study of the Human Past
Entité participante : Université de Liège — Pays : Belgique — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999567.5 €

The proximal senses—taste and touch—were linked historically to the body, femininity, and subjectivity. This both fed adverse socio-cultural, religious, and gender stereotypes and allowed the voices of women, subaltern subjects, and Mediterranean people to be dismissed as irrelevant to knowledge-making. It also influenced modern scholarship, which has given undue weight to sight and the observation practices of seventeenth-century Northern European men as signals of the advent of modern science. PROXISENSES challenges this narrative, arguing that other forms, eras, and practitioners of experimental practices also contributed much to the production of knowledge about the natural world. Building on histories of the senses, food, knowledge, and the Mediterranean, it breaks new ground with three key questions, each tied to a research objective (RO). RO1 Practices: What was the epistemic value of the proximal senses before the alleged Scientific Revolution (i.e., 1350–1650)? RO2 People: To what extent did manual workers (e.g., fruit sellers, farmers, fishmongers, miners, winemakers) contribute to a better understanding of plants, minerals, and animals? RO3 Knowledge: What impact did a millennium of cross-cultural encounters in the Mediterranean have on the construction of sensory knowledge? To address these issues, PROXISENSES uses three food subprojects to investigate touch and taste across the Mediterranean. Each food represents a main category used to classify the natural world: salt (minerals), grapes (plants), and fish (animals). Explored through diverse, scattered primary sources using digital and archival methodologies, the subprojects offer both transversal joint food histories and detailed microhistories. By unearthing previously invisible knowledge-makers, PROXISENSES contributes to the urgent need to decolonise histories of science by offering a transformative vision of the genesis of empirical practices that are central to our view of natural sciences today.

Mots-clés : sensory history history of touch history of taste history of knowledge food history mediterranean history
Projet ERC : HiTime (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Université de Tromsø — Pays : Norvège — Rôle : PI
Acronyme de l'entité : UiT
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2161246.0 €

HiTime is a project about the adjustment of homeostatic set points in physiology. This is known as rheostasis and is of core importance for transitions between physiological states. I seek to develop the concept that a specialised cell type in the hypothalamus, the tanycyte, is the cellular embodiment of a rheostat, and that by understanding the function of the tanycyte, we will gain fundamental insights into hypothalamic control of rheostasis. Since rheostasis is weak in laboratory mice bred to live in constant laboratory environments, new paradigms must be developed. I will therefore investigate tanycyte function in the context of seasonal deep hibernation: the most dramatic example of rheostatic control of energy metabolism in mammals. I will use the golden hamster as the study organism because it has an excellent combination of attributes for pursuing the project aims, from experimental tractability to availability of molecular resources. The study approach will exploit advanced telemetry combined with transcriptomics, metabolomics and neuroimaging to develop an unprecedented “arrow of time” description of changes in tanycyte status in relation to peripheral and central changes in energy metabolites throughout the hibernation. This approach will encompass both long-term rheostatic control of seasonal entry and exit from hibernation, and short-term rheostatic control of torpor-arousal cycles during the hibernation phase. In parallel, I will develop neurogenetic and micro-infusion approaches to allow characterisation of the causal events in rheostatic hibernation control. My career track record gives me an unusual combination of in vivo physiology and bioinformatics skills, which, in combination with my pilot studies establishing new techniques, gives an excellent chance of success despite high ambition. This success will have reciprocal benefits for two major interest areas in physiology with impacts from human obesity research to interplanetary space travel.

Mots-clés : tanycytes,seasonal,thyroid hormone,hibernation,torpor,omics,aav