Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : TB-QUEST (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Hospital Clínic de Barcelona — Pays : Espagne — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 112500.0 €

Tuberculosis (TB) remains a major cause of morbidity and mortality around the world. The majority of TB control policies rely on the binary paradigm of TB, which focus on interventions tackling ‘latent’ TB infection and ‘active’ TB disease stages. However, recent evidence disputes this longstanding conceptualization of TB natural history, demonstrating that TB exists on a continuous spectrum of bacterial and immunological responses. Several active case-finding studies have shown that around 50% of the cases in whom Mycobacterium tuberculosis was isolated in sputum were asymptomatic. Subclinical (asymptomatic) TB has lately attracted increased scientific interest since it could play an important role in TB transmission, despite the absence of cough. However, beyond limited evidence on TB transmission based on modelling studies using retrospective data collection, there is not a single field study showing a direct transmission from an index subclinical TB case to a secondary laboratory-confirmed case. If subclinical TB does spread the disease, the consequences for global TB control and research are of paramount importance. I propose to characterize the subclinical TB stage within the natural history of TB and to understand its role in spreading the disease. I have designed a field epidemiological study (TB-QUEST) with the potential to show evidence of effective transmission from subclinical TB cases to close contacts, using pathogen genome sequencing. Additionally, by using innovative wearable technology, I will assess whether objective tools to measure classical TB symptoms match the self-reported absence of symptoms. Thus, I might challenge the current definition of subclinical TB and the usefulness of current TB screening algorithms. Lastly, I will study the clinical trajectory of subclinical TB in order to improve our understanding of its natural history, duration of infectiousness, and factors associated with self-clearance or progression to symptomatic disease.

Mots-clés : tuberculosis epidemiology infectious diseases global health subclinical
Projet ERC : Mut-Scales (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Consorcio para la explotacion del centro nacional de analisis genomico — Pays : Espagne — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 498750.0 €

As individuals age, mutations accumulate inexorably in their cells, playing a key role in evolution, ageing, and disease. Despite their importance, we still have a poor understanding of how mutations originate, or why some cells accumulate more mutations than others. This proposal aims to address these fundamental questions by examining two axes of mutation rate variation: among cell types and across species. In Aim 1, we will decode the rules of germline mutation during mammalian spermatogenesis. Cells in the germline exhibit mutation rates significantly lower than those in the soma, through mechanisms that remain unknown. Leveraging recent breakthroughs in long-read DNA sequencing, we will track the accumulation of mutations from spermatogonial stem cells to mature spermatozoa in mice. By integrating this data with existing cell type-specific profiles of gene expression, epigenetic marks, and chromatin architecture, we will delineate how cellular processes influence mutation rates in the germline, aiming to reveal differences with patterns in the soma. In Aim 2, we will characterise the DNA damage response across primates. Recent findings suggest that longer-lived mammals have lower somatic mutation rates, but the underlying mechanisms remain elusive. To tackle this question, we will experimentally expose primary fibroblasts of ten primates to UV radiation and a promoter of oxidative stress, quantifying the impacts on cell viability, gene expression, genome accessibility, and mutation rates and spectra. With this comprehensive approach, we will disentangle the pathways leading to damage-induced mutations, as well as uncover molecular mechanisms that evolution has wielded to select for healthier, longer-lived primates. In summary, this proposal aims to learn about how mutations occur—that is, how they originate mechanistically—as well as why their rate of appearance differs across cell types and species—namely, what selective pressures drive mutation rate evolution

Mots-clés : mutation,germline,dna damage and repair,primates
Projet ERC : LIFETIME (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Institute for Bioengineering of Catalonia — Pays : Espagne — Rôle : PI
Acronyme de l'entité : IBEC
Type d'entité : Recherche
Financement ERC de l'entité : 2499318.0 €

Understanding cancer metabolism at the individual patient level is central to making accurate early-stage diagnoses and providing effective patient-specific treatments. While some methods do exist to study intra-cell metabolomics and inter-cell metabolic flux alterations (e.g., PET, MRI), their scalability and sensitivity is limited, hindering reliable investigations long-term. LIFETIME aims to develop a single platform for "lifetime metabolomics", where the metabolic fingerprint of a disease is traced throughout patient onset in vivo, analysis ex vivo, and through to treatment. Technologically this involves rapid metabolomic profiling of the cancer model, using microfluidic 3D-cell-cultures in organ-on-chip (OoC) structures and magnetic resonance spectroscopic imaging (MRSI). Scientifically, the disease-specific case study chosen is hepatoblastoma (HB), the most common liver cancer in children, where the platform could improve patient survival rate and quality of life. Metabolic contrast in three phenotypes of HB mouse models (intrahepatic, intravenous, subcutaneous) and their OoC counterparts will be assessed. A unique benefit of the platform will be its capability for parallel, repeatable measurements on samples to track therapeutic-induced metabolic alterations over time. This will unveil tumours' detailed molecular phenotypes and shed light on their correlation with tumour heterogeneity and interactions within tumour microenvironment. Overall, LIFETIME will enable the definition of new reliable biomarkers of HB that propel the development of targeted therapies. If successful, the scalability of the platform will hold the important ability to bridge in vivo and in vitro assessment, from biopsy-derived cell cultures (parallelised screening) to patients (correlating with current clinical MRSI). Long term, LIFETIME will empower assessment of the benefits and constraints of OoC technology in cancer and other aggressive disease research.

Mots-clés : hyperpolarization,mri,organ on chip,spectrometry,imaging tools,metabolic sensors,parallelised detection
Projet ERC : MR O MICS (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : Partner
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 937150.0 €

High-grade serous ovarian cancer (HGSOC) is the most common subtype of ovarian cancer. The early rapid onset of chemoresistance poses a major clinical challenge. Recent research highlighted high tumor heterogeneity (TH) and identified key mutational signatures that associate with prognosis and may aid in individualized treatment selection. Since HGSOC often presents with multisite disease and distinct populations of malignant cells, multi-region analysis of multimodal data is essential to study HGSOC. Single time point, single site biopsies cannot assess entire tumor while multiple biopsies at several time points are not feasible in clinical routine. Limitations of invasive sampling may be addressed with non-invasive imaging that captures morphologic and functional information about the entire tumor in space and, if repeated, in time. Radiomics has the potential for “whole tumour virtual sampling” using a single or serial non-invasive examinations in place of biopsies. To date, no study has evaluated the value of radiomics at macroscopic (in vivo 1.5T/3TMRI) and microscopic (ex vivo 9.4TMRI) scales to better understand the black box of radiomics features (explainable radiomics) or examine whether radiomics habitats are underpinned by tumour biology to provide a better insight into TH of HGSOC. Specifically, in this project, I will implement a model to capture imaging-based TH with multiscale radiomics approach by obtaining the mirror tumor image at in vivo MRI, ex vivo MRI and at histology. I will evaluate if imaging-based TH reflects underlying tumor histology by testing associations with imaging features and tumor-stroma proportion, infiltrative lymphocytes density and HRD status. Finally, I will unravel HGSOC TH biology through habitat imaging combined to an integrated Multi-O-Mics approach. Successful completion of this proposal will lead to a comprehensive characterization of HGSOC TH which will be then accessible non-invasively through radiomics.

Mots-clés : mri,radiomics,ovarian cancer,genomics,proteomics,immune tumor microenvironment,tumor habitat
Projet ERC : WAVES (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Leibniz-Gemeinschaft — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : WLG
Type d'entité : Recherche
Financement ERC de l'entité : 1499250.0 €

Over the past 120 years, the number of countries affected by waves of democratization and autocratization (Waves of Regime Transformation) has been steadily rising. The current number of countries experiencing autocratization is unprecedented, highlighting the urgency in understanding: How and why do democratic and authoritarian practices spread across the globe in wave-like patterns?  Project Objectives 1. Develop a conceptual and empirical framework to identify waves of regime transformation. 2. Formulate a theory explaining the driving forces behind these waves. A particular focus is on the role of Zeitgeist - the meaning of “democracy” at a particular time and place - and how it affects waves. The theory also clarifies how such waves propagate across different regions and periods. 3. Test the theory empirically, identifying the drivers behind these waves. WAVES develops a multi-level framework for studying waves of regime transformation at individual, national, regional, and global levels. It breaks new ground by using an interdisciplinary, mixed-methods approach, combining techniques from evolutionary biology, political science, and computational social sciences. WAVES builds both a conceptual and empirical framework to study the evolution of these waves, applying causal inference methods to explore their drivers. It examines how hegemonic shocks, diffusion, parallel development, and Zeitgeist shape waves of regime transformation. WAVES challenges the assumption that democracy’s meaning is stable over time and tracks the evolution of Zeitgeist using text analysis of parliamentary speeches.  WAVES moves the field forward by developing a theory of regime transformation waves and creating an empirical dataset that traces these waves since 1900. By revealing when and why such waves begin, accelerate, peak, and decline, it provides policymakers with actionable insights helping them understand and respond to the current global wave of autocratization.

Mots-clés : waves of regime transformation,democratization,autocratization,democracy autocracy,zeitgeist,political institutions
Projet ERC : ESPRESSO-Omics (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed Matter Physics
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 : 1498973.0 €

This proposal aims to address a critical knowledge gap in understanding phenotypic transitions in the context of chemotherapy resistance. Phenotypic transitions encompass various mechanisms that modify cellular phenotypes over time, including differentiation and metabolic reprogramming, among others. As some cellular phenotypes are transient and chemoresistant cells constitute a rare subpopulation, studying these important phenomena is challenging even with modern, high dimensional phenotyping methods (e.g. proteomics and transcriptomics), as they are intrinsically destructive for the sample and can only provide a single snapshot of these fleeting cellular states.  To overcome this limitation, I propose the development of a groundbreaking framework that combines spatial proteomics with ESPRESSO, a novel omics approach I developed for high-dimensional phenotyping applicable to living system. The resulting ESPRESSO-Omics framework will enable real-time monitoring of both organelle and protein expression profiles in living cells, that will allow us to go back in time and identify the subpopulation with the potential to become chemoresistant, as well as the transitions that lead it there, providing a revolutionary point of view in the identification of therapeutic targets. Multiple deliverables including an ESPRESSO-Omics atlas, a high-throughput hyperspectral light-sheet microscope and a machine learning framework will be provided during the course of this award, articulated over two work packages (WPs): WP1: Establishment of the ESPRESSO-omics framework WP2: Investigation of phenotypic transitions in breast cancer  Understanding phenotypic transitions has broad implications, not only in breast cancer research but also in other cancers and biological systems. The open-source cell atlas, instrumentation specifications and data analysis tools will be valuable resources for the scientific community, democratizing advanced tools for the study of phenotypic transitions

Mots-clés : microscopy,breast cancer,spatial proteomics,organelles
Projet ERC : NextGeneTx (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Next generation diagnostic srl — Pays : Italie — Rôle : Partner
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 37500.0 €

Despite 6 products on the market and dozens in advanced phases of clinical development, in vivo gene therapy with vectors derived from adeno-associated viruses (AAV) still faces the major challenge of the limited vector cargo capacity (< 5kb). This prevents AAV application for treatment of inherited diseases caused by mutations in large genes. To address this, we have recently developed an AAV-based strategy relying on the use of short protein elements called inteins. These, when fused at the extremities of fragments of a large protein delivered to cells through AAV, can mediate joining of the fragments in a traceless manner, resulting in the reconstitution of the intact target protein. However, despite being extensively utilized as biotechnological tools in vitro, the in vivo application of inteins for therapeutic purposes comes with several limitations. These include: insufficient levels of full-length protein reconstitution for some applications; complex design; and production of undesired, potentially harmful by-products. NextGeneTx aims to expand the potential of AAV-inteins as an innovative in vivo biotechnological tool for therapeutic purposes, by addressing each of these limitations. To achieve this, we will leverage cutting-edge technologies to: i. engineer inteins with improved efficiency and greater design flexibility; ii. modulate intracellular trafficking of intein-containing protein fragments to enhance the efficiency and accuracy of full-length protein reconstitution; iii. develop strategies to reduce the production of unwanted by-products. We will test the therapeutic relevance of evolved AAV-inteins in both gene therapy and genome editing applications, using human retinal organoids and animal models of retinal diseases. The outcomes of NextGeneTx will define a highly adaptable, safe, and effective next-generation AAV-based approach to deliver large genes, thus significantly expanding the patient population that can benefit from in vivo gene therapy.

Mots-clés : aav,gene therapy,genome editing,large gene delivery,retinal organoids,animal models,inherited retinal diseases,directed evolution
Projet ERC : KI-NET (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
Entité participante : Université de Strasbourg — Pays : France — Rôle : Partner
Acronyme de l'entité : UNISTRA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1146747.5 €

Endergonic processes are central to Life. They are achieved by enzymes, that change conformation during their catalytic cycle. Thus, biological non-equilibrium processes are catalysis-driven. The realization of catalysis-driven processes in artificial systems proved challenging. It remains limited to synthetically demanding interlocked structures, which were upgraded with catalytic features affecting ring sliding motion.  With KI-NET, I want to develop a general biomimetic strategy enabling endergonic processes driven by chemical catalysis. I plan to invert the current approach by introducing defined conformational freedom into simple catalytic units. KI-NET scientific objectives go beyond state of the art in chemically-driven non-equilibrium systems, with the aim to: (i) establish an unconventional theoretical approach based on “effective transition states”, that guides experiments and reveals common underlying principles for catalysis-driven processes and chemical oscillations; (ii) realize endergonic conformation changes powered by catalytic processes, including ATP hydrolysis; (iii) promote endergonic assembly reactions, that will reveal how energy consumption directs chemical adaptation; (iv) realize an artificial synthase: a catalyst that harvests energy from one reaction and uses it to drive a different one.  I will implement a theory-guided experimental approach at the interface between systems chemistry and molecular machines. Leveraging my broad chemistry background, I will address questions that expand towards physics – in terms of formalizing models – and biology – in terms of operating systems to be imitated and unraveled. Realizing KI-NET allows overcoming thermodynamic boundaries. Unforeseen opportunities become possible in material science and energy management, such as the realization of artificial mitochondria. Indeed, KI-NET pioneers a largely unexplored area of science at the roots of dissipative systems, complex phenomena, and –ultimately, Life.

Mots-clés : systems chemistry,non equilibrium chemical systems,non equilibrium self assembly,chemical reaction networks,molecular machines
Projet ERC : INCORWAVE (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Institut national de recherche en sciences et technologies du numérique — Pays : France — Rôle : PI
Acronyme de l'entité : Inria
Type d'entité : Recherche
Financement ERC de l'entité : 1416541.0 €

Waves propagating through a complex medium provide a non-invasive way to probe its interior structures. In ambient noise imaging, the input data are the cross-correlation of the stochastic wavefields. To reconstruct the properties of the medium, the waveform inversion is formulated as an optimization problem involving a misfit function whose convexity plays a critical role in the achievable spatial resolution of the inversion results, especially in the absence of a priori information about the medium. Current inversions are often limited by computational cost, cross-talk between the physical quantities, and the use of single-scattering approximations. Project INCORWAVE proposes to create a new mathematical and computational framework for nonlinear inversion of full waveform cross-correlation. Two specific problems are considered: first, for the reconstruction of geophysical visco-elasticity tensors with applications to Earth's subsurface monitoring; secondly, for the reconstruction of three-dimensional flows in the Sun to characterize the poorly understood properties of deep solar convection. To improve the convexity of misfit functions, the inversion procedure of project INCORWAVE will follow a hierarchical progression which is established by selecting subsets of input data, unknown parameters, and frequencies. The choice of each of these subsets, as well as the associated misfit function, is controlled by criteria in form of convergence estimates. Indispensable to meaningful inversion is accurate modeling operators that describe the physics under consideration and that are adapted to the treatment of real data. For the reconstruction of the elasticity tensor, the project will develop a solver in terms of P- and S-potentials for heterogeneous media. A 3D global Sun vector-wave solver is created for the inversion of the convection component of the solar flow that does not bear symmetry.

Mots-clés : inverse problems wave equations helioseismology convergence estimates hybridizable discontinuous galerkin discretization time harmonic waves