Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : SATTOC (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
Entité participante : Commissariat à l’énergie atomique et aux énergies alternatives — Pays : France — Rôle : PI
Acronyme de l'entité : CEA
Type d'entité : Recherche
Financement ERC de l'entité : 2325590.0 €

X-ray photons carry sufficient energy to interact with molecular core-shell’s electrons. Accessible for decades in the energy domain, the resulting core-excited states (CES) can now be observed in the time domain using attosecond (10-18 s) spectroscopy. These states are important as they govern the lineshapes in all x-ray spectroscopies. Here, we propose to first investigate and then manipulate the CES time evolution in solvated biomolecules in order to reveal key chemical information – i.e. solute-solvent interactions, local symmetries and chiral fields. CES lifetimes dictate the emission of secondary electrons active in radiotherapy. By observing the effect of solute-solvent interactions on CES we will be able to achieve a better understanding of the first molecular mechanisms of radiotherapy. CES are also a subtle probe of the absorbing atom’s bonding environment. CES line splittings are lost in conventional x-ray spectroscopy due to homogenous broadening. We developed a technique based on the laser manipulation of CES capable of producing lineshapes up to an order of magnitude below the spectroscopy’s lifetime broadening and revealing core-level splitting. We will employ this approach to observe core-level splitting in solvated amino acids and metalloproteins and will use this new information to reveal the binding geometry of ligands with unprecedented accuracy. Finally, we will show how one can use nonlinear optics with attosecond pulses to reveal the chirality of the field surrounding sulphur and phosphorus atoms in biological samples. X-ray excitation localizes the point of view on the chiral field to a single atom. This perspective will allow us to examine the chiral landscape near the target atom. Here, chirality due to a single chiral centre will be probed in L-cysteine while the chirality due to the macromolecular arrangement will be measured in DNA helixes. Our proposal brings attoscience techniques in the investigation field of large solvated systems.
Projet ERC : ARMIES (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Soci al World and Its Interactions
Entité participante : Université d'Utrecht — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499918.0 €

This project is an ethnographic study of the everyday deployment of firearms and their societal impact. It examines and compares the various ways firearms produce communities, and focuses on groups that are overlooked in the field of gun studies, such as gun owners associations and hunting clubs. ARMIES hypothesises that these communities are disruptive and transformative ones that exert tremendous power. For an accurate understanding of firearms, these communities must take centre stage. ARMIES spearheads a new research agenda that centralises these communities of arms as material, affective, and political ones that profoundly shape everyday life. It asks: How do firearms produce communities, how do these communities relate to one another, and what is their societal impact? This question will be answered through a comparative and multiscalar analysis of such communities and their members in Brazil, Germany, and South Africa, and global communities, such as international disarmament organisations. Due to the highly embodied, sensational, and affective nature of firearms, ARMIES will use a multisensorial ethnographic approach that comprises ethnographic methods that explicitly target the senses. This approach prioritises embodied experiences, perceptions, and processes of knowledge making. The team of four researchers – the PI and three PhDs – will be steered by an ethos of team ethnography that stimulates collaboration, reflection, and ethnographic imagination. ARMIES is innovative in terms of its theoretical, methodological, and contextual approach to firearms. It will benefit the fields of (political) anthropology, material culture studies, sensorial scholarship, and gun studies. The high gain of this research is threefold: 1) it reconsiders existing theories of human-nonhuman interactions, 2) it creates a novel methodological approach, and 3) it will be ground-breaking science-based evidence for our public understanding of the role of firearms in our society.

Mots-clés : communities,materiality,ethnography,senses
Projet ERC : 3DchromArchaea (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : Laboratoire européen de biologie moléculaire — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : EMBL
Type d'entité : Recherche
Financement ERC de l'entité : 1494500.0 €

This proposal brings together the field of chromatin evolution and state-of-the-art structural biology to advance our understanding of a fundamental question: origin of chromatin structural and regulatory complexity. Eukaryotes and most groups of archaea organize their genomes in the form of histone-based chromatin. Conservation of histones across the tree of life goes beyond protein sequence and histone fold. Tertiary arrangement of histones and DNA geometry in archaeal nucleosomes resemble those in eukaryotes; however, archaea can form special hypernucleosomes and “slinky”-like arrangements. Similarly to eukaryotes, some archaea have multiple histone variants and extended histone tails, although it is unclear whether their structural and regulatory roles are conserved. Eukaryotes inherited histone-based chromatin from archaea, however, the origins of eukaryotic chromatin complexity are enigmatic. Therefore, this proposal will address the 3D organization of chromatin in archaea to advance the understanding of chromatin evolution. We will test the following hypotheses: archaeal chromatin along with hypernucleosomes contains multiple open structures to maintain DNA accessibility and allow polymerase passage; histone variant exchange and histone tails in archaea play an important role in chromatin compaction similarly to eukaryotes. To test our hypotheses, we will synergistically apply state-of-the-art cryo-electron microscopy (cryo-EM) in situ and in vitro to selected archaeal systems. In situ cryo-EM will provide structural information about chromatin in native context, while cryo-EM of in vitro reconstituted chromatin will provide high-resolution structural information. Structural analysis complemented with biochemical, biophysical characterization and nucleosome positioning data will provide insights into 3D chromatin architecture in archaea in the context of eukaryotic chromatin evolution.

Mots-clés : chromatin,archaea,cryo em,cryo electron tomography,histones,structure,evolution
Projet ERC : ITSaMATCH (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Institut Pasteur — Pays : France — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 335000.0 €

Half of the world’s population is at risk for mosquito-borne diseases. Yet, less than 3% of the mosquito species on earth can transmit pathogens to humans. Even within a species that specializes in biting humans and is the major vector for dengue virus (Aedes aegypti), mosquito populations on the globe transmit DENV with a wide range of efficiencies. Thus, some virus-mosquito pairs “match” with each other, and enable viral transmission, while others don’t. Understanding the biological processes that determine virus-mosquito compatibility is a longstanding question that has not yet been addressed, mostly owing to a lack of appropriate methods. Here, I propose to leverage advances in single-cell technology, gene editing and computational tools to understand the basis of virus-mosquito matchmaking. I will address three related challenges:  1 – Obtain single-cell transcriptional and epigenetic atlases for key organs of “matched” or “unmatched” virus-mosquito pairs. To be retransmitted, a virus needs to infect and transit through key organs in a mosquito’s body. Unknown factors that interfere with viral infection and impact further transmission exist in mosquito cells. They will be detected with single-cell technologies. 2 – Identify the key drivers of virus-mosquito matchmaking. Using cutting-edge single-cell data analysis methods, I will determine which genetic or epigenetic processes are associated with “matched” and “unmatched” virus-mosquito pairs. 3- Reprogram virus-mosquito matchmaking using genome editing. With key factors of matchmaking identified, I will genetically interfere with their function and determine whether virus-mosquito pairs can artificially be “matched” or “unmatched”. ITSaMATCH will combine new technologies to unravel the basis for virus-mosquito matchmaking. The project has the potential to substantially advance our understanding of virus-mosquito interactions and inform novel disease control strategies.

Mots-clés : insect immunity,arboviruses,single cell sequencing,mosquito transgenesis
Projet ERC : IDENTIKIT (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Istituti di Ricovero e Cura a Carattere Scientifico — Pays : Italie — Rôle : Partner
Acronyme de l'entité : IRCCS
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 207500.0 €

Understanding what makes our cells prone to develop cancer is key for identifying effective strategies of tumor prevention. By analyzing the genome of normal human cells, I obtained compelling evidence that the pattern of somatic mutations can be used to identify the cell-of-origin of kidney cancer. Although every cell accumulates somatic mutations during a lifetime, some are exposed to a specific mutational process that leave a detectable mark in their genome. Kidney cancers and their cell-of-origin show the same genetic mark, consisting of excess somatic point mutations with unique characteristics and unknown origin. We plan to use this mutational signature to track cancer-prone cells in human kidneys and a) follow their population dynamics; b) study their genome and transcriptome at a single cell level; c) understand the underlying causes of excessive mutation. Having already established a non-invasive assay to detect cancer-prone cells in urine samples, we can now analyse numerous donors, longitudinally and without biopsies. Our preliminary analyses point to adaptation to low-oxygen conditions (hypoxia) as the likely cause of excessive mutation in kidney cells and suggest defects in specific DNA repair pathways as a mechanism. We will test whether overactivation of hypoxia signalling, caused by either a genetic syndrome or exposure to renal ischemia, induces the kidney-specific mutational signature in humans. We will then dissect the molecular mechanism by functional experiments in vitro and in mouse models. Finally, we will test whether and how the diet contributes to the expansion of the mutation-prone cell subset in mouse kidneys. Overall, this study will provide unprecedented resolution of early events leading to kidney cancer initiation and will determine whether hypoxic stress is mutagenic and cancer-promoting. Further, this project will pursue the novel idea that cells can be tracked and possibly arrested before cancer initiation.

Mots-clés : kidney,dna repair,metabolism,nutrition,genetic diseases,hypoxia,vhl,oncometabolites,
Projet ERC : MetaboGutModel (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Laboratoire européen de biologie moléculaire — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : EMBL
Type d'entité : Recherche
Financement ERC de l'entité : 1499323.75 €

The gut microbiota is essential to human health: microorganisms in the human body help to digest nutrients, engage in host metabolism, immunity, behaviour and brain functions. Since the gut microbiota, in contrast to the human genome, can be modified through dietary and therapeutic interventions, modulating the microbiota is a promising path to improve human health and to prevent or treat diseases. However, predicting the effects of microbiota perturbations on the host metabolic phenotype remains extremely challenging due to our limited understanding of bacterial metabolic functions, molecular interactions within microbial communities, and the mechanisms of microbial interactions with the host. I propose to tackle these challenges with a combination of experimental and computational approaches in a synthetic community of 14 common human gut bacteria, which has been associated with > 150 health-relevant metabolites involved in amino acid, vitamin, and hormone metabolism in vivo. We will follow a bottom-up strategy to i) systematically characterize the capacity of single bacteria to consume and produce metabolites of interest and identify the responsible enzymes; ii) investigate the metabolism of these compounds in compositionally diverse synthetic communities; and iii) quantify and modulate microbiota contribution to the host metabolism of these compounds in mouse models. To this aim, we will combine high-throughput bacterial culturing, metabolomics, transcriptomics and proteomics assays with genome-scale metabolic modelling, graph-based multi-omics integration methods and physiology-based models of microbiota-host interactions. This project will provide a generalized framework to systematically resolve microbiota contributions to the host metabolic phenotype, and elucidate the fundamental principles governing microbiota-host metabolic interactions, thus enabling targeted microbiota interventions to modulate the host metabolic phenotype and improve human health.

Mots-clés : gut microbiota,microbiota host interactions,metabolic modelling,physiology based modelling,multi omics integration
Projet ERC : CO-PP (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : Laboratoire européen de biologie moléculaire — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : EMBL
Type d'entité : Recherche
Financement ERC de l'entité : 2269196.0 €

Predation plays a key role in the planet’s ecology and evolution. The most prevalent and diverse predators on the planet are protozoans, single-cell eukaryotes that live from consuming bacterial prey. Protozoan predation massively impacts bacterial diversity, shapes microbial ecosystems, is essential for nutrient cycling and has been linked to the emergence of bacterial virulence. Yet, despite its importance, it remains largely elusive how protozoan predators and bacterial prey coevolve. To understand this coevolution, we need an integrative research approach that accounts for offense and defense mechanisms in both predator and prey, and spans from cellular response systems to community ecology.  Here, I take this approach, and present the first integrative research program on microbial predator-prey coevolution. By leveraging recent advances in gene editing and single-cell phenotyping, we will focus on the coevolution between amoebal predators and bacterial prey in the soil – a hotspot for microbial predation. First, we will establish a predator-prey model system that permits a two-sided and systems-level analysis of predation. Using genome-wide genetic screens, we will identify all genes underlying offense and defense mechanisms, study how they exert their effect, how they are regulated, and how they impact selection across environments. Second, we will expand from our model system, to study natural predator-prey soil communities. We will explore how sexual reproduction and horizontal gene transfer impact coevolution, and emulate soil conditions in the lab, to determine how biotic and abiotic factors affect eco-evolutionary dynamics of predator-prey communities in both time and space.  My research will connect ecology and evolution with molecular and systems biology, opening up the door for breakthrough advances in our understanding of predator-prey interfaces, the impact of coevolution on microbial ecosystems, and the emergence of nascent pathogenicity.
Projet ERC : TEMPO (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
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 : 1500000.0 €

TEMPO aims to solve the newly discovered epigenetic 'time puzzle' of child mental health. Recently it has been observed that common mental health problems in children (e.g. hyperactivity, poor impulse-control) are associated with epigenetic patterns at birth - a mechanism that regulates gene activity in response to genetic and environmental influences. Curiously, however, this association is lost when measuring the same epigenetic patterns later in development. This discovery is highly unexpected and potentially ground-breaking: the existence of timing effects could lead to new insights into the origins of mental health and open much-needed opportunities for early risk detection. Yet, what factors drive epigenetic timing effects, how they manifest and why they occur is currently a puzzle.  To solve it, TEMPO will combine innovative, multidisciplinary approaches and the generation of exceptional new data in a unique set of longitudinal European cohorts to address the what, where and why of epigenetic timing effects. Three work packages will be implemented to: (i) Systematically characterize unknown properties of epigenetic timing effects, including their genomic scale, specificity to mental health and persistence into adulthood, using advanced quantitative methods; (ii) Locate epigenetic timing effects with greater precision, by establishing whether effects are driven by epigenetic patterns in specific tissues and cell-types that are found at birth but not later in life; and (iii) Explain timing effects, by disentangling the genetic and environmental origins of epigenetic timing effects on mental health, drawing on the power of genetically sensitive, quasi-experimental designs.  As well as leading a breakthrough in this emerging field and addressing a major knowledge gap at the intersection of biological and psychological sciences, TEMPO has the potential to set in motion a paradigm shift in the way that we conceptualize, understand and approach child mental health.

Mots-clés : child mental health adhd dna methylation epigenetics sensitive period developmental psychopathology behavioral problems longitudinal modelling child development prenatal environment predictive tools
Projet ERC : COLINA (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental Constituents of Matter
Entité participante : Conseil supérieur de la recherche scientifique — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 1609083.0 €

Coherent elastic neutrino-nucleus scattering (CEνNS) is a recently demonstrated novel process of neutrino interaction. It provides numerous avenues to advance our sensitivity to new physics beyond the Standard Model and enables a miniaturization of otherwise massive neutrino detectors, opening up the possibility of technological applications.  The development the development of an innovative single-phase noble liquid time projection chamber (TPC) to detect CEνNSis proposed. Two distinct ideas are combined to maximize the potential of the technique. 1) The signal will be amplified through electroluminiscence (EL). 2) The TPC will be shaped as a conical frustum. Single-phase EL is unaffected by charge trapping which is the major deterrent of dual-phase noble liquid TPCs for CEνNS searches at shallow depths. However, it requires extremely high electric fields. Such fields can be reached by using very thin wires – μm-scale diameter. This is an impediment to produce large amplification regions. Common TPC shapes are thus limited in size and target mass. The conical shape allows to maximize the mass by drifting all charges towards a small amplification region at the smaller circle of the cone. Such scheme allows for good coverage with few sensors.  COLINA, a conical TPC capable of holding ∼50 kg of LXe, will be developed and deployed at the largest spallation neutrino source, the European Spallation Source. Simulations point to a conservative energy threshold as low as ∼0.525 keVnr. The detector will allow for operation with different noble gases. The increase in density of liquid-phase, compared to gaseous-phase, results in large CEνNS rate with rather small detectors. In fact, COLINA will produce the larger CEνNS statistics in all the considered isotopes, Xe, Kr and Ar, and will do so in unexplored energy regions for the process, where the physics relevance is maximal.

Mots-clés : neutrino,liquid noble gas,time projection chamber,coherent elastic neutrino nucleus scattering
Projet ERC : ResolVE-XAS (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Istituti di Ricovero e Cura a Carattere Scientifico — Pays : Italie — Rôle : PI
Acronyme de l'entité : IRCCS
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 1500000.0 €

Hematopoietic stem cells (HSCs) accumulate somatic mutations during aging, which may drive clonal expansion of their progeny. This clonal imbalance promotes cancer and often establish systemic inflammation contributing to frequent diseases of aging. Disentangling and tackling clonal imbalance of hematopoiesis is thus an urgent challenge with substantial medical implications for a progressively aging population. VEXAS syndrome is a novel, adult-onset, devastating disease with growing number of patients. It is caused by the expansion of pro-inflammatory hematopoietic clones acquiring somatic mutations of the UBA1 gene. Its pathophysiology is elusive, and treatments are unsatisfactory leading to dismal prognosis. In this project I will address knowledge gaps and unmet medical needs of VEXAS syndrome, here proposed as paradigmatic example of a hematologic disease of aging caused by clonal expansion. To unveil the uncharted pathogenesis underlying VEXAS clonal expansion and inflammation I will develop and apply to patients’ samples innovative multiomics technologies simultaneously informing on phenotype and genetic mutations of clones while reconstructing hierarchical relationships and retrospectively tracing expansion dynamics. To validate these findings in stringent settings I will leverage cutting-edge gene editing systems for the generation of VEXAS models by installing in human wild-type HSCs the pathogenic mutations found in patients, and study differentiation, clonal expansion and inflammatory properties of their outgrowth in transplanted immunodeficient mice. Finally I will investigate an autologous HSC gene editing approach in VEXAS models based on the hypothesis that targeted disruption or correction of mutant UBA1 alleles can erase fitness advantage of pathogenic clones. This project will transform current understanding and management of clonal imbalance of hematopoiesis by developing new models and technologies and proposing ambitious strategies to tackle it.

Mots-clés : vexas syndrome,clonal hematopoiesis,clonal tracking,single cell multiomics