Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MERLIN (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Cell Biology, Development, Stem Cells and R egeneration
Entité participante : Université Masaryk — Pays : Rép. Tchèque — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499821.0 €

The continued health of many of our organs, including the skeleton, relies on the function of specialized stem cells. These stem cells reside in niches that support their long-term maintenance. Disruption of the niche due to aging, injury, or genetic mutations, can lead to declines in stem cells and a failure to maintain and repair tissues. Compared to our understanding of the stem cells that maintain and repair our skeleton, we know much less about the cell types that constitute their niche. My prior large-scale genomics studies have uncovered a novel niche cell type for the skeleton. Intriguingly, these niche cells are defined by a unique metabolic profile, highlighting in particular enzymes for Phenylalanine (Phe) / Tyrosine (Tyr) metabolism and glycogen synthesis. Traditionally, it has been thought that Phe/Tyr are degraded primarily in the liver, and the skeletal malformations in patients with Phenylketonuria (mutation in PAH), Tyrosinemia (I-III, mutations in FAH, TAT, HPD) and Alkaptonuria, a.k.a. "black bone disease" (mutation in HGD) has been interpreted as the results of systemic intoxication by accumulated metabolites. My dogma-shattering result suggests that local regulation of Phe/Tyr degradation might be a critical strategy to support the skeleton. I will establish a research group that leverages the powerful genomic, genetic, and high-resolution imaging strengths of zebrafish to test the requirements of niche cells in skeletal stem cells homeostasis and the roles of metabolism in stem cell maintenance. Findings from my proposed studies will inform future therapies aimed at correcting metabolic diseases and restoring stem cell function and skeletal health by modulating the niche.

Mots-clés : stem cells,niche,metabolism,animal model,skeleton,zebrafish
Projet ERC : LEARN (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Soci al World and Its Interactions
Entité participante : Fondation nationale des sciences politiques — Pays : France — Rôle : PI
Acronyme de l'entité : FNSP
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499853.0 €

Health crises, natural disasters, and violent conflicts pose global threats to children’s educational development. The frequency and severity of such disruptive events is intensifying due to climate change and the growing instability of the global security architecture. Yet, we lack a systematic understanding of how major disruptive events affect children’s educational development, largely because such events tend to also disrupt the collection of high-quality data on children’s education.  Due to the global scale of the COVID-19 pandemic and extensive data collection efforts as it unfolded, the COVID-19 pandemic offers a unique opportunity to advance our understanding of the consequences of major health crises for children’s educational development. LEARN will leverage this opportunity to reveal the principal pathways through which the pandemic has affected the educational development of children in different world regions, as well as the key factors that reduce or exacerbate its adverse consequences.  LEARN will generate and apply high-quality, cross-national data and advanced quantitative and meta-analytical techniques to achieve five core objectives: (1) Trace children’s recovery of COVID-19 learning deficits using a living meta-dataset and online tracker (2) Assess COVID-19 effects on children’s early-life trajectories (3) Map the processes through which the pandemic affected children’s educational development (4) Reveal the factors that reduce or exacerbate COVID-19 effects (5) Identify the most effective remedial education interventions to promote children’s learning recovery  This ambitious and innovative research programme will substantially advance our understanding of how major health crises affect children’s educational development, generate several new data resources, and provide a basis for policy makers to future-proof education systems to meet the growing threats posed by major disruptive events.

Mots-clés : covid 19 pandemic,health crises,educational development,educational inequality
Projet ERC : RadicalProtON (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
Entité participante : Asociacion instituto de investigacion sanitaria biobizkaia — Pays : Espagne — Rôle : Partner
Acronyme de l'entité : BIOBIZKAIA
Type d'entité : Recherche
Financement ERC de l'entité : 31250.0 €

Chemistry and Biology are governed by molecules and how they interact. Crucially, what glues a molecule together are chemical bonds, made from atoms pairing all their electrons. Although preferred, this is not the only option: in the comparatively rare cases where a molecule presents unpaired electrons, it acquires a fascinating new status that transforms its chemical and biological properties, best described by the acutely apt name of radical. Despite the extraordinary toolset found in radical-bearing molecules, the rather demanding methods to radical formation currently available mean that only very specific molecular architectures can withstand them, inadvertently limiting the scope of their applicability.  The aim of this ERC project is to show that reversible diradical formation upon deprotonation is prevalent, and yet unexplored, in general donor-acceptor organic molecules and use this new knowledge to develop novel design criteria in light-emitting molecules and drug discovery.  To achieve this unique aim, I will exploit a widespread structural pattern in a novel way, enabling a molecule to reversibly convert its charge and spin and become a diradical. I will first characterise how different molecular constituents (un)favour diradical formation on isolated molecules. I will then establish, for the first time, the role that diradicals play in defining the function of the numerous bioactive molecules sharing the proposed structural pattern.  By exposing the overlooked diradical character in general families of deprotonated organic molecules, I will deliver transformative mechanistic understanding on i) the photo physical properties of fluorescent proteins and ii) the reactivity of small molecule drugs, particularly a new class of covalent inhibitors. The field of organic radicals sits at a critical crossroads between Chemistry and Biology, and as such, taking it a step forward has the potential to cross-pollinate research fields and reshape research frontiers.

Mots-clés : diradicals,epr,drug design,fluorescent proteins
Projet ERC : METABAC (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Helmholtz-Gemeinschaft — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : HGF
Type d'entité : Recherche
Financement ERC de l'entité : 1499894.0 €

Host cells and microbial inhabitants form an intricate ecosystem in the human body, extensively influencing host phenotypes in health and disease. Despite much progress in sequencing-based cancer microbiome research, elucidating functional roles of bacteria in metastasis formation remains an important unsolved challenge. In the METABAC project, we will explore such bacterial roles as drivers of colorectal cancer metastasis. We will investigate new concepts on whether bacteria can equip cancer cells with malignant features, migrate within the host and potentially represent targets for cancer therapy.  In Aim 1, my group will characterize the microbial inhabitants of colon tumors and metastases. We will uncover bacterial species and their genetic features in metastases by using sequencing-, imaging- and culturing-based approaches. In Aim 2, we will mechanistically dissect functional impacts of metastasis-derived bacteria on distinct stages of the metastatic process. For this, we will use specialized organoid, organ chip and orthotopic organoid-bacteria co-engraftment platforms that we have pioneered.  In Aim 3, uncovering the tropism, timing and routes of bacterial migration to different metastasis sites takes center stage. Bacterial strains and organoids derived from different metastasis sites will be co-engrafted into mice and traced to lymph node, liver and lung metastases.  The METABAC project will provide an unprecedented characterization of microbial roles in metastasis. Our combination of metastasis-derived bacterial strains with novel organoid, organ chip and in vivo platforms puts us in a unique position to close the gap between cancer microbiome sequencing and mechanistic studies and promises groundbreaking functional insights into host-microbe interactions in cancer and beyond.

Mots-clés : cancer microbiome metastasis organoids organ on a chip functional assays bacterial culturing colorectal liver lung
Projet ERC : CytoInP (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Wageningen University & Research — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : WUR
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1476476.0 €

In plants, genetic material is stored in the nucleus and the two cytoplasmic organelles: plastids and mitochondria. While both the nuclear and cytoplasmic genomes are essential for plant survival, the inheritance of these genomes is subject to different sets of rules. Cytoplasmic inheritance differs from nuclear inheritance through two unique phenomena: uniparental inheritance and vegetative segregation. Despite extensive research efforts, the molecular basis of uniparental inheritance and vegetative segregation remain elusive. A major challenge in unraveling the mechanisms is the lack of methodologies. Excitingly, recent advancements in cytoplasmic genome engineering have provided me with a unique opportunity to develop feasible approaches for exploring this crucial area of biology. The ultimate goal of this project is to achieve a comprehensive understanding of cytoplasmic inheritance, which will, in turn, enable us to control the plastid and mitochondrial inheritance. To attain this ambitious goal, we will pursue three specific aims: (1) Identifying the factors that govern maternal inheritance, (2) Promoting the selective transmission of cytoplasmic genomes, and (3) Investigating the molecular basis of vegetative segregation. In this project, we will utilize a combination of genetic and cytological approaches to study cytoplasmic inheritance in the model plants Arabidopsis thaliana and Nicotiana tabacum. The success of our project would represent the first instance of controlled cytoplasmic inheritance in plants. Our fundamental research will provide new tools for testing existing hypotheses regarding cytoplasmic inheritance. From an agricultural standpoint, breeders can leverage this unprecedented capacity to selectively transmit cytoplasmic genomes, thus enabling the inheritance of desired crop traits. The potential application of cytoplasmic inheritance in plant breeding highlights the societal impact of our research.

Mots-clés : plastid inheritance mitochondrial inheritance cytoplasmic male sterility
Projet ERC : NCOre (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 1875000.0 €

Chromatin organization plays a crucial role in regulating DNA-related processes such as transcription, replication, and repair. In most somatic cells, heterochromatin localizes at the nuclear periphery while euchromatin is broadly distributed within the nucleus. This spatial organization is believed to mostly rely on the association of heterochromatin with the nuclear lamina, which in turn participates in gene repression. In a striking contrast, the nuclear pore vicinity is always devoid of heterochromatin, therefore forming heterochromatin exclusion zones within the heterochromatin layer of the nuclear periphery. In rupture with the classical view that the nuclear lamina stands as the main determinant of heterochromatin accumulation at the nuclear periphery, I propose that it rather results from an equilibrium between attraction at the nuclear lamina and exclusion from the adjacent nuclear compartment: the nuclear pores. I further propose that by excluding heterochromatin, nuclear pores participate in global chromatin organization, and thereby impact gene regulation. Whether the absence of heterochromatin at nuclear pores impacts their function is unknown. Using a combination of advanced microscopy techniques, proteomics and genomics, I will interrogate the crosstalk between nuclear pores and chromatin organization by addressing three fundamental questions: (1) What is the contribution of heterochromatin exclusion zones to global chromatin organization? (2) What are the mechanisms underlying heterochromatin exclusion zone maintenance at nuclear pores? (3) What is the role of heterochromatin exclusion in nuclear pores transport? The NCORe project therefore promises to shed light on new mechanisms regulating chromatin organization and nucleocytoplasmic transport.

Mots-clés : heterochromatin,nuclear pores,lamina associated domains
Projet ERC : HeRiDe (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Studies of Cultures and Arts
Entité participante : Conseil national de la recherche — Pays : Italie — Rôle : PI
Acronyme de l'entité : CNR
Type d'entité : Recherche
Financement ERC de l'entité : 1394881.0 €

Although heritage science field already offers a wide range of tools for condition assessment of wall paintings, an efficient on-site full-field depth-resolved inspection is not achieved yet. In practice, heritage professionals often struggle to interpret complex and fragmentary scientific data. Conservators often face challenges in assessing hidden risks and localizing the depth of detected detachments, covered fresco layers, refills, and cracks. The main challenge in wall painting’s condition assessment is that it is inextricably linked to the architectural/archaeological support. The preservation of the pictorial layer, often unique and irreplaceable as in ancient frescoes, depends on the integrity not only of the surface but of the bonding substrate and the structure behind it. Informed and timely interventions by conservators are important to mitigate natural aging processes, and become crucial in case of extreme events (e.g. seismic activities, climate disasters etc.) or anthropogenic damage (both intentional and unintentional, including past restorations etc.). The HeRiDe methodology will be grounded in a scientific protocol that employs cross-correlation formulas to analyze full-field interferometric and thermographic datasets. This approach will differentiate hidden risks according to their characteristics and depth in the stratigraphy of wall paintings. The HeRiDe project seeks to exploit the maximum yet to be explored potential of the complementary full-field heritage science approach, testing and validating the results on wall painting mock-ups, and transposing the methodology to real case studies. To facilitate its real implementation, a dedicated open source software tool will be proposed to ensure broad access for all international heritage professionals. Finally, HeRiDe will enhance the accuracy of risk assessments and support more informed conservation decisions, contributing to the sustainable preservation of wall paintings worldwide.

Mots-clés : wall paintings,frescoes,conservation,heritage,non invasive diagnostics,deterioration,optics,physics,thermography,interferometry,shearography,digital documentation
Projet ERC : HYPERCAN (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 769028.75 €

Transmissible cancers are fascinating recently discovered biological entities. They have acquired the ability to cross host boundaries and spread between animals, even sometimes interspecifically, by the direct transfer of cancerous cells. In addition, despite asexual reproduction they have been shown to persist for hundreds or thousands of years in host populations. Importantly, in the absence of known sexual-like reproduction mechanism, transmissible cancers must cope with clonal degeneration. One challenging question that arises is to understand the evolutionary processes and molecular mechanisms by which genetic diversity can maintain in such a long-term clonal context. Several transmissible cancer lineages have been described in Bivalvia and they have all in common hyperploidy. Some distinct sub-lineages (with a common founder host) coexist in host populations with specific degrees of hyperploidy (2 to 10 times the host cell DNA content). Hence, the hypothesis that hyperploidization concurs to the persistence and long-term evolution of these transmissible cancers must be considered. HYPERCAN aims to decipher the evolutionary significance of hyperploidy and of its variation to amplify clonal heterogeneity in mussel transmissible cancers (MtrBTN). We will use a multi-disciplinary approach combining phenotyping and “multi-omics” in order to test evolutionary hypotheses. We will answer 3 main questions: 1. Ploidy and fitness. Does a correlation exist between ploidy degrees and fitness? 2. Evolutionary dynamics. How does evolution proceed in MtrBTN cancers? 3. Hyperploidization mechanisms. How is hyperploidy generated and what is the fate of newly evolved hyperploid lineages? The project will have multiple outputs and applications among which to understand the genetic mechanisms driving the evolution of long-living cancers and to provide useful elements for the assessment of evolutionary and phenotypic effects associated with hyperploidization in cancers.

Mots-clés : long term evolution,transmissible cancers,ploidy variations,whole genome duplication,clonal reproduction,cell cell fusion,marine mussels
Projet ERC : TREAT (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Materials Engineering
Entité participante : Conseil national de la recherche — Pays : Italie — Rôle : PI
Acronyme de l'entité : CNR
Type d'entité : Recherche
Financement ERC de l'entité : 1500000.0 €

Thermal emission is a fundamental and ubiquitous process of energy and entropy transport, impacting science and engineering in various way. Yet, its stochastic nature, expressed in a broadband spectrum, lack of polarization and directionality, severely limits its control and manipulation. TREAT aims at introducing a novel method for engineering the radiative heat transport and achieving unprecedented dynamical control over the spectrum and the momentum of thermal radiation. To achieve this goal, I propose to combine two classes of emergent materials: time-varying epsilon-near zero (ENZ) media and hyperbolic materials (HMs). The time modulation of ENZ media will allow to overcome the fundamental limits to thermal emission set by the Planck’s and Stefan-Boltzmann’s laws and achieve active control over its properties. While the HMs, will enable to extract and guide the intense thermal radiation confined at the emitter surface, i.e., in its near-field. TREAT objectives address three intriguing questions: i) Can we create a time-varying media with ad hoc time modulation? ii) Can we manipulate thermal emission beyond the Planck’s law using the time-modulation? iii) Can we improve our control of the radiative heat flow in the near-field? Answering these questions requires the combination of expertise in nanophotonics and ultrafast science and perfectly suits my scientific profile. TREAT specifically targets the thermal emission engineering in the transparency window of Earth atmosphere, relevant for radiative cooling, and the development of novel coherent thermal sources in the THz range. TREAT will provide a fundamental advance to our understanding of thermal fields, beyond fluctuational electrodynamics, and a novel method for engineering the radiative heat flux, anticipating significant impacts in several applications of thermal light that would benefit from the active control of its properties, such as radiative cooling, energy harvesting, and optoelectronics.

Mots-clés : thermal radiation,epsilon near zero media,hyperbolic materials,thermal light coherence,quantum electrodynamics,thermal fluctuations
Projet ERC : REGULADOSIX (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 1843419.0 €

Differences in gene dosage can be as powerful as to drive species evolution (e.g., whole-genome duplications) and as harmful as to lead to human diseases (e.g., aneuploidies or haploinsufficiencies). Regulating the effects of gene-dosage differences is thus extremely critical, and this is paradigmatically illustrated by what happens to the X chromosome in mammals. In XX individuals, one of the X chromosomes is transcriptionally silenced as a result of a developmental and epigenetic process called X-chromosome inactivation (XCI), which is presumed to have evolved to compensate X-linked gene dosage between XX and XY individuals. Since its ‘discovery’ in 1961 by Mary Lyon, we have learnt much about XCI developmental dynamics and molecular underpinnings, however very little is understood about the developmental and molecular reasons at the basis of its evolution. REGULADOSIX aims to gain a functional and mechanistic understanding of the need of X-linked dosage compensation in mammals – we will (i) determine the developmental and molecular consequences in the absence of XCI in mouse embryogenesis, and (ii) functionally identify genes on the X chromosome that are dosage-sensitive, as well as their functions, which would have dictated the emergence of XCI in mammalian evolution. Building on my previous expertise, I propose a multidisciplinary approach at the intersection between development and genetic engineering, which includes cutting-edge genomic technologies (epigenetic screens, functional transcriptomics and proteomics) and novel approaches that we will develop to tune levels of expression in mouse embryonic stem cells and in mouse models. Besides bringing new insights into the need for dosage compensation between the mammalian sexes, REGULADOSIX will contribute to a quantitative understanding of gene expression, and pave the way to establishing fundamental principles of gene dosage regulation in development and disease.

Mots-clés : x chromosome inactivation dosage compensation gene dosage dosage sensitivity mouse embryonic stem cells