Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : LymphoTOP (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Centro de Regulación Genómica — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CRG
Type d'entité : Recherche
Financement ERC de l'entité : 1499993.0 €

A central goal in cancer research is to identify the molecular mechanisms underlying tumor formation, such as translocations that result in expression of fusion genes or proto-oncogenes located at the translocation breakpoints. While the consequences of this erroneous expression have been widely studied, other effects of translocations remain largely unexplored. Nevertheless, these can provide vital new insights into tumorigenesis. I hypothesize that translocations disturb the global 3D genome architecture, causing alterations in chromosome territory positioning and interchromosomal interactions. And, that these can account for (in)activation of key genomic loci for which the cause of deregulation remains so far unknown. I will address this hypothesis in the context of Non-Hodgkin lymphoma (NHL)-related immunoglobulin (IGH) translocations. By genome editing we will create lymphoblastoid cell lines and cord blood cell-derived B lymphocytes in which IGH translocation-based effects can be cleanly dissected in vitro and in vivo. In these models, we will study how IGH translocations affect genome topology, the epigenetic and gene expression landscape and NHL formation. To that end, we will assess (i) chromosome territory structure and interchromosomal crosstalk by chromatin conformation capture and fixed- and live-cell imaging, (ii) epigenetic and gene expression maps using bulk and single-cell profiling and (iii) in vivo tumor formation. Importantly, after exploring the presence of the observed gene expression changes in NHL samples, we will target the coinciding changes in in vitro and in vivo approaches to probe their relevance for lymphomagenesis. Overall, LymphoTOP shall lead to deeper insights into translocation-based genome topology reorganisation and its role in tumorigenesis, and to potential identification of new vulnerabilities of lymphomas. Thus, extending its impact to many fields, from lymphoma and tumor biology to 3D genome organisation and beyond.

Mots-clés : non hodgkin lymphoma,tumor formation,translocations,genome topology,oncogenic epigenetic lesions,interchromosomal crosstalk
Projet ERC : EpiSperm (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Centro de Regulación Genómica — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CRG
Type d'entité : Recherche
Financement ERC de l'entité : 1499428.0 €

Mammalian sperm RNA is increasingly recognized as an additional source of paternal hereditary information beyond DNA. Environmental inputs, such as diet and stress, can reshape the sperm RNA signature and induce offspring phenotypes that relate to paternal environmental stressors. However, how, when and to what extent sperm RNA populations change, and what is the role that RNA modifications and other post-transcriptional regulatory layers play in shaping sperm RNA dynamics, remains poorly understood. Here, we propose to characterize the dynamics of RNA populations during sperm formation and maturation using native RNA nanopore sequencing. This technology is suited to provide an integrative and comprehensive view of the transcriptome, epitranscriptome, degradation patterns and tailing dynamics simultaneously, and with single molecule resolution. We will establish novel library preparation methods that can capture the full sperm (epi)transcriptome, and will capitalize on our recently developed algorithms to map and quantify RNA modifications in individual RNA molecules. We will then apply these methods to reveal how paternal dietary exposures affect sperm RNA populations and the metabolic phenotypes of their offspring, and test whether the novel identified RNA candidates can transmit diet-induced paternal phenotypes to the subsequent generation. Finally, we propose to expand our previous work on direct RNA multiplexing to establish single cell direct RNA nanopore sequencing, to characterize the diversity and heterogeneity of the sperm RNA (epi)transcriptome at an unprecedented single cell and single molecule resolution.

Mots-clés : rna modifications sperm rna intergenerational inheritance nanopore sequencing single cell epitranscriptomics
Projet ERC : URANUS (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
Entité participante : Sorbonne Université — Pays : France — Rôle : PI
Acronyme de l'entité : Sorbonne U
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 891010.0 €

Evaluating and fabricating sustainable materials for the energy sector is crucial in addressing the current energy crisis and climate change. Despite safety and sustainability concerns, especially as the early generations of nuclear power plants (NPP) near the end of their operational lifespans, NPPs produce almost one-fifth of the world’s electrical energy. However, controlling material degradation and reprocessing issues in NPPs remains surprisingly understudied due to the extreme operating conditions. Up to 95% of uranium from spent nuclear fuel can be recycled through reprocessing in concentrated nitric acid at temperatures exceeding 100°C, although the underlying mechanisms and the role of alloying elements in the fuel container are not yet well understood. Electrochemical methods have been applied in these extreme electrolytes to investigate materials degradation mechanisms providing in situ global responses. However, these methods are limited as they rely on assumptions developed in aqueous media and do not provide direct, element-specific information, necessitating complementary ex situ surface characterizations. To bridge the gap, the URANUS project will develop a novel element-resolved electrochemistry setup for extreme electrolytes, leveraging the unique expertise of the PI in this field. Element-by-element degradation mechanisms of metallic materials in concentrated nitric acid will be elucidated for the first time, tracking the fate of each alloying element. Other non-aqueous electrolytes including molten salt systems will also be investigated with this approach. This will open new avenues for controlling the corrosion of materials in the energy sector. The unique element-resolved database generated from this project will serve as input parameters for training machine learning models aimed at efficiently discovering optimal alloys in specific environments, thereby reducing the consumption of raw and scarce materials during the materials design process.

Mots-clés : in situ element resolved electrochemistry aesec corrosion mechanism in extreme electrolytes spent nuclear waste reprocessing stainless steels ni alloys database for alloy design
Projet ERC : FORECAST (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Sorbonne Université — Pays : France — Rôle : PI
Acronyme de l'entité : Sorbonne U
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 681673.0 €

Assessing the benefit-risk balance of treatment is crucial in medicine to select the most appropriate treatment for patients. This process faces major challenges, how to implement evidence in real time to guide treatment choice and how to summarize efficacy and safety outcomes to patients and clinicians, while incorporating patient preferences. Inflammatory bowel diseases (IBD) affect 3 million residents in Europe. New advanced therapies have been recently approved, but in the absence of head-to-head randomized controlled trials (RCT), data are lacking to position each drug in the therapeutic management. Multiple types of real-world data (RWD) sources are available to assess the effect of treatment, but each type has its proper strengths and limitations. Linking multiple RWD sources can overcome limitations and leverage the strengths of each data source. We recently emulated clinical trials supporting the use of RWD to assess treatment effectiveness and safety in IBD. Based on the linkage of nationwide healthcare databases, electronic health records, and a prospective cohort of IBD patients, the aims of the current proposal are (i) to validate algorithms identifying IBD characteristics and outcomes in nationwide healthcare databases, (ii) to emulate head-to-head clinical trials comparing advanced therapies in IBD, (iii) to incorporate trials findings and patient preferences in a clinical decision support system for IBD patients and clinicians, whose impact will be assessed by a pragmatic RCT nested in nationwide healthcare databases. This challenging project will involve multi-disciplinary aspects, from qualitative approach to artificial intelligence, to clarify the position of each treatment in IBD and disseminate findings to patients and clinicians. Besides scientific importance, it will have societal impact by setting the stage for a novel post-marketing drug surveillance framework applicable not only to future IBD treatments but also to other chronic diseases.

Mots-clés : pharmacoepidemiology gastroenterology inflammatory bowel diseases administrative health databases
Projet ERC : INSOLIT (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Sorbonne Université — Pays : France — Rôle : PI
Acronyme de l'entité : Sorbonne U
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 325554.44 €

Various models encountered in mathematical physics possess special solutions called solitary waves, which preserve their shape as time passes. In the case of dispersive models, small perturbations of the field tend to spread, so that their amplitude decays. The Soliton Resolution Conjecture predicts that, generically, a solution of a nonlinear dispersive partial differential equation decomposes into a superposition of solitary waves and a perturbation of small amplitude called radiation.  Our study will focus on topological solitons appearing in models motivated by Quantum Field Theory: kinks in the phi4 theory and rational maps in the O(3) sigma model. We expect that the developed techniques will have applications in the study of other topological solitons like vortices, monopoles, Skyrmions and instantons.  Our general ultimate objective goes beyond the Soliton Resolution, and consists in obtaining an asymptotic description in infinite time, in both time directions, of solutions of the considered model. Such a description should be correct at least at main order, and reflect interesting features of the problem, which are the soliton-soliton interactions and soliton-radiation interactions.  We pursue this general goal in various concrete situations, namely: the problem of unique continuation after blow-up for the equivariant wave maps equation, the collision problem for the phi4 equation, the study of pure multi-solitons in the regime of strong interaction, and the multi-soliton uniqueness and stability problem. Their solution requires a mixture of non-perturbative and perturbative techniques. While the former rely heavily on the concrete model, the latter will be applicable to any dispersive equation having solitary waves.

Mots-clés : soliton,scattering,long time behavior
Projet ERC : 3DnanoGiant (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Materials Engineering
Entité participante : Istituto Nazionale di Ricerca Metrologica — Pays : Italie — Rôle : PI
Acronyme de l'entité : INRIM
Type d'entité : Recherche
Financement ERC de l'entité : 1172500.0 €

Photonics has a major impact on technological innovations and can revolutionize the field of computing and data processing due to its high bandwidth, speed, and low power consumption. This has already happened for data communication via fiber-optic connections, while light processing in embedded systems is still performed by electronics via power-hungry optical-electrical conversion.  The future development of integrated photonics is then waiting for new integrable materials that can advance the functionality of photonic chips towards all-optical signal processing at very low light intensities. While linear operations and parallel matrix multiplication can be efficiently performed by light, nonlinear optical functions are notoriously difficult to implement because they require a suitable medium for efficient photon-photon interaction. Currently, there is a lack of materials with large third-order nonlinearity, high speed and easy processability and integration in 2D and 3D structures.  3DnanoGiant aims to develop new nonlinear photonic materials that can be integrated into heterogeneous functional platforms or chiplets. To this end, I will exploit the giant optical nonlinearity of liquid crystals (ten orders of magnitude larger than that of silicon), for new formulations and lithographic strategies by which the liquid crystals will be confined in a printable nano-porous polymer network. Their 3D nanopatterning will enable the production of multidimensional hybrid nonlinear photonic devices, from all-optical 2D logic gates and ultrafast nonlinear activation functions to self-oscillating 3D photonic crystals. In parallel, the propagation, interaction and polymerization of solitons in a 3D(+1) space will lay the foundation for a new unsupervised bottom-up 3D printing technology. The goals of 3DnanoGiant will redefine the state-of-the-art in integrated nonlinear photonics with practical and versatile heterogeneous chip for fast and energy-efficient optical processing.
Projet ERC : ImmGenDC (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Université Louis-et-Maximilien de Munich — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : LMU
Type d'entité : Organismes publics (hors enseignement & recherche)
Financement ERC de l'entité : 996913.0 €

Antiviral immunity and autoimmune diseases exhibit high interindividual variability. Despite intensive research, the genetic and molecular basis of this variability is incompletely understood. A key player of the immune system is the plasmacytoid dendritic cell(pDC). Recent single-cell work revealed functionally distinct pDC subsets. Considering that pDCs respond to many pathogens, this highlights a previously underappreciated functional diversity of pDCs. I hypothesize that the genetic regulation of pDCs plays a fundamental role in explaining antiviral response and autoimmune variability. Based on my previous work on immune cells, this genetic regulation is expected to be highly context-specific depending on cell type, cell response, ancestry populations and sex among other factors. The overarching goal of this proposal is to elucidate the context-specificity of immune response and its genetic regulation in pDCs to improve our understanding of human antiviral response variation and pinpoint undiscovered disease pathways of autoimmune diseases. To this end, I will generate population-scale, linked scATAC-, sc3’RNA- and scLong-read cDNA-seq data of baseline and TLR7-stimulated pDCs from healthy individuals across three ancestry populations. I will identify novel pDC subtypes and their immune-regulatory circuits by integrated multiome analyses. Molecular quantitative trait loci(QTLs) and their degree of context-specificity will be used to build prediction models of genetically determined immune responsiveness and decode autoimmune disease loci to develop mechanistically anchored interventions for precision medicine. ImmGenDC will gain fundamental insights into the variability of antiviral immune response that will enable the development of new treatments as exemplified by the current pandemic. Importantly, ImmGenDC will also identify genetic determinants of immune variability across diverse ancestry populations thus paving the way for equitable access to medicine.

Mots-clés : eqtl,human immune system,innate immunity,plasmacytoid dendritic cells,interferon,antiviral immunity,autoimmune diseases,human genetics,immunogenetics,functional genomics,population genetics,gwas,multi omics,precision medicine
Projet ERC : RESIST (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
Entité participante : Leibniz-Gemeinschaft — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : WLG
Type d'entité : Recherche
Financement ERC de l'entité : 129991.25 €

Providing food security in the face of climate change and increasingly frequent extreme heat and drought events is one of the greatest global challenges. Drought is the most influential environmental factor limiting crop yields for a growing world population and leading to significant economic losses. To safeguard agricultural production, it is crucial to develop high-yielding crops with improved water use efficiency. Oat (Avena sativa L.) is an emerging crop that offers significant benefits for human health and provides a nutrient-rich plant-based protein source with a low carbon footprint. However, oats are sensitive to drought and progress in breeding drought-resistant varieties, while urgently needed, is limited. The oat genome is characterised by its enormous size, high repeat content, and complex polyploid structure. Therefore, efforts to investigate complex agricultural traits such as drought stress resistance have long been hampered by the lack of genomics resources. Recently, a fully annotated reference genome sequence of Avena sativa became available, to which I contributed significantly, representing a fundamental breakthrough. RESIST will take on the challenging high-priority task of deciphering the molecular basis of drought stress resistance in oat, providing substantial solutions to secure yields of this emerging, healthy and versatile crop. To this end, RESIST will exploit innovations in plant genomics and in particular oat genetics, employ cutting-edge high-throughput phenotyping methods and establish gene editing protocols that provide an innovative basis for accelerated and targeted breeding of oats. RESIST provides the indispensable foundation for the development of better-performing oat varieties under drought conditions to secure oat yields as a sustainable source of a highly nutritious, healthy, protein-rich plant-based diet for billions of people.

Mots-clés : drought,oat,cereals,health,breeding barriers,gwas,phenotyping,genomics,comparative genomics,pangenomics,computational biology,transcriptomics,gene editing
Projet ERC : CLL-STORY (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Hospital Clínic de Barcelona — Pays : Espagne — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 48592.75 €

A holistic view of the history of cancer is not only essential to better understand its pathogenesis, but also has a clear impact by improving future prevention schemes, personalized management strategies, and treatment options. Importantly, the roadmap of a tumor is incomplete without knowing the molecular composition of its normal cellular counterpart (NCC), cell of origin (COO), clonal trajectories, and interactions with the tumor microenvironment influencing disease progression and response to therapy. In chronic lymphocytic leukemia (CLL), the most common adult leukemia in Western countries, and Richter transformation (RT), its aggressive progression, these fundamental aspects remain largely unknown. In this project, named CLL-STORY, I aim to fully reconstruct the life histories of CLL to improve clinical outcome. To that end, using novel methodological breakthroughs and functional readouts, I will (1) generate a detailed multi-omic atlas of normal B cells to properly delineate the NCCs of CLL and their precise nature, allowing me to clarify the role of (epi)genetic drivers in CLL promotion, (2) characterize the COO of CLL and its lifelong clonal trajectories to resolve the disease origin and growth patterns dictating the different clinical courses, with the ultimate aim to control early disease precursors and anticipate disease evolution, and (3) determine the mechanisms of resistance to immune-based therapies, as well as intrinsic and extrinsic features influencing their anti-tumor efficacy, to aid the development of predictive models and improvement of current treatments, which shall improve clinical outcome. In summary, CLL-STORY explores uncharted territories unraveling clonal mosaicism, early cancer development, tumor phylogenies along human lifespan, and mechanisms of treatment failure, hence providing key knowledge, tools, and enhanced treatment options with clear implications reaching beyond CLL, that will bring the entire cancer biology field forward.

Mots-clés : lymphoid neoplasms chronic lymphocytic leukemia richter transformation
Projet ERC : CHILDCARE STRATEGIES (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Human Mobility, Environment, and Space
Entité participante : Université Érasme de Rotterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : EUR
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1470130.0 €

Background - High quality childcare greatly improves outcomes in later life. Yet childcare access and usage are distributed unevenly, leading to amplified inequalities in later life outcomes. Parents from low-income households are 50% less likely to use formal childcare services than high-income households and use them when the child is older and less intensely. Research has shown that cost, location, and quality of childcare effects usage, yet policy solutions aimed at removing these barriers have not reduced inequalities in usage.  Aim - In this project, sociological, economic, demographic and social policy perspectives are synthesized within a framework of ‘complex contagions’ to investigate how the use of formal childcare diffuses across low income populations, with the aim of identifying barriers to uptake in formal childcare.  Approach - This project breaks through the state of the art to more clearly describe why some childcare strategies, that use formal childcare, don’t spread to low income households. With a complex contagion, people only adopt a new behaviour if they are repeatedly exposed to it from multiple, diverse actors in their network. Low income households have personal networks with long weak ties and high, multi-layer clustering, that make adopting new childcare strategies unlikely. This project therefore examines how the childcare strategies present in work, family and neighbourhood networks influences the childcare strategies of low income households.  Innovation & Impact - The analysis will draw on unprecedented, linked administrative and survey data to study the diffusion of childcare strategies. Network data are used in combination with multichannel sequence analysis and other longitudinal methods to identify the role of networks in shaping childcare strategies. The project will completely reframe our understanding of not only childcare strategies, but also parallel areas of social policy and the wider study of behaviour diffusion in

Mots-clés : childcare,fertility,female employment,networks