Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : IGNITION (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Institut Curie — Pays : France — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 442500.0 €

Human tissues can tolerate a series of mutations in tumor suppressors and oncogenes without necessarily transforming. Potential for tumor initiation is not only determined by such accumulated molecular defects but also by the capacity of each cell and tissue to deal with them. Intrinsic cell plasticity – i.e. the ability to change phenotypes by accessing alternative expression programs - appears to be one of the determining factors of the penetrance of oncogenic stresses. Yet, how cell plasticity contributes to tumorigenesis remains poorly understood, in part because we can hardly access tumor initiation in humans. With IGNITION, we propose to uncover mechanisms maintaining cell lineage integrity under oncogenic stress in humans and explore their therapeutic potential to delay tumor initiation. To do so, we propose to access tumor initiation in humans using samples from the standard of care of BRCA1/2 mutation carriers. We will reconstitute entire individual trajectories up to tumor initiation, taking advantage of our privileged access to bio-banked and fresh human samples through the Curie hospital. Serial sampling for individual patients will be paired to organoid avatars, to expand our ability to observe tumor initiation events. Combining high resolution single-cell transcriptomics and epigenomics, we will identify recurrent non-genetic determinants of tumor initiation and study their potential as breaks or accelerators of tumor initiation with Cas9/CRISPR approaches in organoid models. Finally, we will test two strategies for therapeutic intervention: (i) control cell lineage integrity by restraining plasticity of the epithelial cell compartments, or (ii) targeting predispositions to transformation. Our long-term goal is to build on this integrated appreciation of tumor initiation to propose therapeutic strategies to monitor and delay tumor initiation in patients with pre-disposition to cancer.

Mots-clés : breast cancer,plasticity,single cell epigenomics and trancriptomics,predisposition
Projet ERC : CertiFOX (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer Science and Informatics
Entité participante : KU Leuven — Pays : Belgique — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999928.75 €

The field of combinatorial optimization is concerned with developing generic tools that take a declarative problem description and automatically compute an optimal solution to it. Often, users specify their problem in a high-level, human-understandable formal language. This specification is first translated into a low-level specification a solver understands and subsequently solved. Thanks to tremendous progress in solving technology, we can now solve a wide variety of NP-hard (or worse) problems in practice. Moreover, these tools are increasingly used in real-life applications, including high-value and life-affecting decisions. Therefore, it is of utmost importance that they be completely reliable. The central objective of this proposal is to develop methodologies and tools with which we can guarantee with 100% certainty that the right problem has been solved correctly. To achieve this ambitious objective, I will build on recent breakthroughs in proof logging, where solvers do not just output an answer, but also a proof (or certificate) of correctness. However, a major limitation of current techniques is that correctness is not proven relative to the human-understandable specification written by the user, but relative to the low-level translation that the solver receives, meaning that there is no guarantee that the solver is solving the original problem. In this project, I will investigate end-to-end guarantees of correctness. When successful, this will have a major impact on the way combinatorial optimization software is developed, evaluated, and used: the proofs produced will enable (1) debugging, since proofs contain detailed information about where bugs occurred, (2) auditability, since proofs can be stored and checked by an independent third party, and even (3) rigorous evaluation of algorithmic improvements (I, for instance, have first-hand experience of winning a solver competition due to a bug that would have been caught easily using proof logging).

Mots-clés : combinatorial optimization,proof logging
Projet ERC : NSHAPE (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental Constituents of Matter
Entité participante : KU Leuven — Pays : Belgique — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

By combining atomic, nuclear and particle physics techniques, I shall perform the experimental study of the shape of key atomic nuclei, to challenge our understanding of the nucleus. This combined effort will reach unprecedented sensitivity, precision and accuracy to determine the shape observables (charge radii, electric quadrupole moments) and compare them to state-of-the-art nuclear models (spherical shell model, density functional theory, ab initio models based on chiral effective field theory). This programme will combine different techniques at various accelerator facilities where I employ and develop unique approaches and instrumentation:  - At CERN ISOLDE (Geneva, CH), high-resolution laser resonance ionization spectroscopy will be performed with the Resonant Ionization Laser Ion Source (RILIS) combined with the Perpendicularly-Illuminated Laser Ion Source and Trap (PI-LIST) to study the onset of octupole deformation and proceed towards the proton drip line with selected nuclei.  - At GANIL SPIRAL2 (Caen, FR), high-sensitivity laser resonance ionization spectroscopy will be performed in the supersonic gas jet of the gas cell at the focal plane of the Super Separator Spectrometer (S3) to study the most exotic isotopes not available at ISOLDE, reaching proton-unbound nuclei at the drip line.  - At PSI (Villigen, CH), muonic x-ray spectroscopy will be performed on key isotopes to measure absolute charge radii that are crucial to complete the analysis of the NSHAPE isotopes. This work will combine a strong experimental development in target production for muX, in the detector array, and in the analysis tools.  Combining the high-resolution laser spectroscopy and the high-accuracy from μx-ray spectroscopy is a unique programme that only NSHAPE can fully realize, providing radii and moments with unprecedented accuracy. From those results, I shall obtain a deeper understanding of the strong interaction at work in the nuclear medium.

Mots-clés : nuclear shapes,nuclear structure,heavy elements,proton emitting nuclei,laser spectroscopy,muonic atoms
Projet ERC : ETHYLUTION (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : KU Leuven — Pays : Belgique — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999370.0 €

When ancestral plants colonized the land 450 million years ago, they needed to adapt to harsh environmental conditions when giving up their aquatic lifestyle. I hypothesize that during this water-to-land transition, the volatile plant hormone ethylene became an important growth regulator to face terrestrial stressors. In fact, modern-day crops use ethylene to regulate stress responses, and perhaps ethylene served this role in pioneering land plants to cope with the harsh conditions coinciding with this habitat transition. During my postdoc, I showed that ethylene signaling was functionally assembled in ancestral Charophyte green algae, prior to land colonization. Now I question why and how early land plants produced ethylene. While seed plants make ethylene using ACC as precursor, non-seed plants follow a different, yet unknown ethylene biosynthesis pathway, which I want to reveal using the liverwort Marchantia polymorpha, a model species representing early life on earth. I also question why non-seed plants make ACC, but not use it for ethylene synthesis. Recent studies revealed that ACC itself can act as a signaling molecule, independent from ethylene, by an unknown signaling pathway to regulate plant development. I also postulate that both the alternative ethylene biosynthesis and ACC signaling pathway might have an origin in ancient algae, prior to land colonization, and might be conserved in seed plants, possibly exerting important functions yet to be uncovered. Using functional genetics in representative species of algae and crops, ETHYLUTION will unravel the importance and role of ACC and ethylene that allowed plants to thrive on earth, perhaps one of the most impactful events in the evolutionary history of plants.

Mots-clés : ethylene,1 aminocyclopropane 1 carboxylic acid,plant hormones,evolution,marchantia polymorpha
Projet ERC : BICROSS (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Texts and Concepts
Entité participante : KU Leuven — Pays : Belgique — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1751602.0 €

BICROSS is an interdisciplinary project linking Greek, Latin, Syriac, Coptic, Gothic, Armenian and Arabic philology, New Testament textual criticism, manuscript studies, ancient history and digital humanities. Little is known about the bilingual New Testament manuscripts, although translations occur remarkably early. Their physical and textual characteristics, relations, tendencies and impact remain understudied despite their centrality to the understanding of the transmission of the New Testament and its reception in different cultures. For centuries New Testament manuscripts have been studied from a monolingual perspective which has obscured the fact that the textual transmission did not take place solely within the boundaries of a single-language tradition but also across languages. Uncovering and establishing the mutual exchange and cross-language interaction require a new multilingual approach to the New Testament tradition. BICROSS breaks through the current monolingual limitation by shifting the discipline’s focus to the overall New Testament tradition. Accepting the possibility that each variant reading could have had its potential source in a reading from a different language tradition and may likewise have caused a dependent reading in any of the other language traditions breaks new ground. The project’s bold and pioneering cross-language approach brings a fresh perspective to the discipline’s current search for new paradigmatic concepts to explain the relations of New Testament readings and manuscripts at large. BICROSS develops specific digital tools to process the vast and linguistically complicated manuscript data in order to pioneer an examination of the entire New Testament bilingual tradition on a larger scale than has ever been possible. The results will provide new insights into the formation and transmission of New Testament texts and will influence the understanding of historical, cultural and linguistic exchange in the East and West.

Mots-clés : new testament textual criticism bilingual manuscripts ancient translations ancient bible translations greek latin coptic papyri
Projet ERC : TwinPolitics (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Université de Vienne — Pays : Autriche — Rôle : PI
Acronyme de l'entité : Uni Wien
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999734.0 €

In the light of time pressure, persisting data gaps, and challenges to the implementation of global sustainability goals for ocean protection, the European Commission is currently building a prototype digital twin of the ocean (DTO). The EU DTO is part of a larger set of substantial global and national efforts to develop highly accurate digital models of the ocean for ‘better decision-making’ and an emerging high-tech knowledge infrastructure that turns various types of ocean data into prediction tools for public and private actors with a stake in the transition towards sustainable ocean futures. However, DTOs, although needed to advance ocean science and governance, are a political issue in themselves. Firstly, DTOs run the risk of perpetuating global inequalities because the capacities to develop, access, and use ocean data, information, and science are unequally distributed. Secondly, DTOs may create an array of legal and political uncertainties regarding data access, ownership, security, and sharing. Thirdly, DTOs should be embedded into a set of norms, rules, and values to prevent abuse and misuse in practice — a neglected aspect in the current ‘twin rush’. TwinPolitics will overcome shortcomings in the study of DTOs by examining both the socio-technical making of DTOs for national scientific and political purposes and the politics of developing and using DTOs in an international setting. TwinPolitics will re-conceptualise digital twins as socio-technical relations operating under a specific set of institutional, political, and economic conditions and within a hybrid research, data, and observation environment. TwinPolitics will break new ground by developing a methodological approach that combines, on the one hand, qualitative and quantitative research on the practices, policies, and politics presiding over digital twins in national/regional contexts (EU, USA, China) with, on the other hand, the study of DTO use during multilateral negotiations.

Mots-clés : digital twin,ocean governance,marine environmental protection,multilateral negotiations,science policy interfaces,the north south divide,data driven policy making
Projet ERC : UNEARTH (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Study of the Human Past
Entité participante : Université de Vienne — Pays : Autriche — Rôle : PI
Acronyme de l'entité : Uni Wien
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1462702.5 €

Humans and other living beings are constantly shedding DNA, and this DNA is preserved in archaeological sediments. In 2021, I developed the first methods for reliably capturing and analyzing human nuclear ancient DNA (aDNA) from sediments, leveraging this abundant genetic resource as a reliable tracer of biological identity. For ancient societies, such aDNA has the potential to function as forensic “breadcrumbs” that trace the spaces inhabited by ancient individuals. At the well-documented, multi-phase Early Bronze Age settlement of Vráble, I will undertake a cutting-edge research program to obtain human aDNA from over 100 individual house floors, spanning the entire occupational area and 500-year history of the settlement. The UNEARTH project will reveal inheritance patterns and social organization, and map individuals from the cemetery back onto the spaces where they left their genetic traces. By integrating genetic, bioarchaeological, and isotope analyses, UNEARTH seeks to uncover socioeconomic stratifications and their role in prehistoric neighborhood organization. The methods developed in UNEARTH for extracting and analyzing human aDNA from sediments will have wide-ranging impact on archaeogenetics, enabling new analyses on archaeological sites, cultures and time periods that lack associated human remains. Crucially, UNEARTH will develop a robust framework for using human aDNA from sediments in cases where bones cannot be ethically sampled. By establishing new methodology and best practices for sampling and analyzing sediment aDNA, this project will unlock rich genetic records that are ubiquitous at nearly every archaeological site in order to elucidate the lived experiences of prehistoric Europeans at unprecedented resolution.

Mots-clés : bronze age,population genetics,social organization,sediment dna,ancient dna
Projet ERC : TransNeuroFate (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
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 : 210561.25 €

The cerebral cortex is a central structure of the mammalian brain, characterized by a remarkable diversity of neuronal types. Understanding the origin of the extraordinary neuronal diversity is fundamental to understand how cortical architecture and functions emerge during development and remains a critical challenge in cellular and molecular neurobiology. While the efforts have been focused on transcriptional control, evidence for regulation at the translational level is emerging. I hypothesize that translational control, albeit overlooked, acts in a combinatorial fashion with transcriptional induction to regulate gene expression programs during cortical patterning. I have demonstrated an intimate functional link between cortical development and pools of mature transfer RNA (tRNAs), the major determinant of translation. I, therefore, propose to address how translational control, through the modulation of the availability of mature translationally competent tRNAs, fine-tunes gene expression programs during lineage progression, thereby regulating neuronal diversity. Studying this yet unexplored question should unravel a hitherto unrecognized level of neuronal fate identity determination in the cerebral cortex. We will combine ribosome profiling, mRNA and tRNA deep sequencing, screening of genetic perturbation and gene manipulation in vivo in the mouse embryonic cortex to i) uncover the specific translational programs that influence neuronal lineages progression; ii) determine how tRNA repertoires (both at the transcriptional and post-transcriptional levels) are shaped to meet the specific translational needs of different cell types during corticogenesis and iii) validate the functional importance of fluctuation in mature tRNA content during cortical development. This project should bring conceptual advances in the understanding of brain development mechanisms that could be instrumental to interpret the pathological mechanisms of neurodevelopmental disorders.

Mots-clés : cortical neurogenesis,neuronal diversity,transcriptional priming,translational control,trnas
Projet ERC : CANPLAST (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Institut Gustave Roussy — Pays : France — Rôle : Partner
Acronyme de l'entité : IGR
Type d'entité : Recherche
Financement ERC de l'entité : 507500.0 €

Novel cancer molecular-targeted therapies allow to significantly prolong the survival of cancer patients. However, the inevitable acquisition of resistance mechanisms limits the clinical benefit of these treatments. To fully understand how resistance develops, it is crucial to better integrate tumor heterogeneity, cancer cell plasticity and microenvironment changes by applying cutting-edge single cell technologies directly on sequentially sampled biopsies from cancer patients. Additionally, to achieve deeper and longer-lasting clinical responses for cancer patients, we will need to target the rare drug-tolerant persister cancer cells. Samples collected before, during and after treatment will be used to fully describe the characteristics of the cells that are the source of genetic resistant variants that ultimately give rise to tumor relapses. By combining the establishment of patient-derived models, drug-screening of epigenetic inhibitors, transcriptomic and epigenetic characterization of persister cells we will aim to highlight their vulnerabilities. Finally, identify the driver mechanisms of genomic evolution by elucidating the link between oncogenic kinases and DNA repair pathways activity will be our innovative strategy to exploit putative susceptibilities to impeach the survival of resistant cells. The use of DNA repair substrate combined with CRISPR gene knockout will aim at confirming the value of targeting DNA repair pathways to profoundly transform the outcome of patients with metastatic cancer. Overall, by applying new technological breakthrough at the single cell level on patient biopsies, digging into the intrinsic nature of persister cells and taking advantages of DNA repair defects we will identify innovative treatment strategies to avoid the emergence of resistance in patients.

Mots-clés : persister cancer cells,targeted therapy,resistance
Projet ERC : DEEPCONTROL (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and Processes Engineering
Entité participante : Office national d’études et de recherches aérospatiales — Pays : France — Rôle : Partner
Acronyme de l'entité : ONERA
Type d'entité : Recherche
Financement ERC de l'entité : 63000.0 €

Over the past decades, aviation has become an essential component of today’s globalized world: before the current pandemic of coronavirus disease 2019 (COVID-19), over 100,000 flights took off everyday worldwide, and a number of studies indicate that after the pandemic its relevance in the transportation mix will be similar to that before COVID-19. Aviation alone is responsible for 12% of the carbon dioxide emissions from the whole transportation sector, and for 3% of the total CO2 emissions in the world. Due to the major environmental and economical impacts associated to aviation, there is a pressing need for improving the aerodynamic performance of airplane wings to reduce fuel consumption and emissions. This implies reducing the force parallel to the incoming flow, i.e. the drag, and one of the strategies to achieve such a reduction is to perform flow control. DEEPCONTROL aims at using high-fidelity simulations and deep reinforcement learning to develop a framework for real-time prediction and control of the flow around wing sections and three-dimensional wings based only on sparse measurements. We will first perform high-order spectral-element simulations of wing sections and three-dimensional wings at high Reynolds numbers. Using sparse measurements at the wall, we will reconstruct the velocity fluctuations above the wall within a region of interest. To this end, we will employ a generative adversarial network (GAN), together with a fully-convolutional network (FCN) and modal decomposition. Then, we will perform flow control based on deep reinforcement learning (DRL), which will enable discovering novel solutions in terms of flow actuation and design of winglet geometry. In order to assess the robustness of the framework for real-time applications, we will carry out detailed wind-tunnel experiments at KTH.  This framework will constitute a breakthrough in aviation sustainability, and will enable developing more efficient aeronautical solutions worldwide.

Mots-clés : computational fluid dynamics deep learning turbulence turbulent wings