Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : CYTO-BRIDGES (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Cell Biology, Development, Stem Cells and R egeneration
Entité participante : Université d'Utrecht — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

During development, cells divide and make fate decisions. Canonically, cell division ends with the severing of the link between daughter cells in the process called abscission. Yet, across the tree of life, cells can remain connected through cytoplasmic bridges by delaying or inhibiting abscission. Curiously, while bridges are important conserved structures sustaining cellular function, there are little evidence to explain how bridge impact cell function. The aim of the proposal is to investigate the hypothesis that bridges are conserved organelles critical for cell function by providing unique mechanical connexion and an important inter-cellular communication channel. In particular, we will leverage our expertise in live imaging of cell division and biophysics as well as a combination of newly developed genetic and optogenetic manipulations to determine: 1) The role of bridges as a mechanical coupling between connected cells. We will test the contribution of cytoplasmic bridges in creating a physical link between cells and the consequences of disturbing this cohesion for cell function. 2) The role of bridges as an exchange route between connected cells. We will investigate how the regulated exchange of cellular material through bridges impacts cell function. As bridges can have a simple or a complex structure that could be critical for their function, we will use 2 model systems: the choanoflagellate Salpingoeca rosetta where a structurally simple bridge sustains cell-cell cohesion, and mouse embryonic stem cells where bridges are structurally more complex. While traditional models of bridges are difficult to manipulate, both our models are easy to culture and provide an experimentally tractable system that can shuttle from a unicellular to a multicellular organisation. The comparison between these two model systems will allow us to understand how a fundamental step of cell division could crucially impact the function of cells in a multicellular context.
Projet ERC : IMPACT (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and Processes Engineering
Entité participante : Université d'Utrecht — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1625000.0 €

Less than 9% of plastic is recycled. Currently applied recycling technology yields degraded materials because undesired mechano-chemical bond cleavage shortens the polymer upon repeated processing. Here, I introduce a new type of catalyst to exploit this undesired effect to recover the polymer building blocks, the monomers, which enables the production of new high-quality polymer. I will focus on polyolefins (PP, PE) that make up 50% of polymer production and for which the state-of-the-art pyrolysis process has high energy costs and does not yield pure monomer. That is because at the 600 °C needed to break the strong carbon-carbon (C-C) bonds of PP and PE unwanted reactions occur. Adding a catalyst powder, a known strategy to exert reaction control, is inefficient for polymers because they cannot reach the active sites in the catalyst pores. I will break the C-C bonds with force instead of heat. The force is provided by collision of balls in a ball mill, a mature grinding technology that I repurpose as reactor to introduce my tunable direct mechano-catalyst: I will chemically treat the surface of the balls to create catalytic, e.g., acid, sites that are in efficient contact with polymer through vigorous ball movement. In our ground-breaking proof-of-concept experiment, we were surprised to see monomer form below 60 °C from PP, and a remarkable 4x increased activity over a traditional catalyst. To realize the full potential of this new catalytic concept, I will establish the underlying fundamental framework by A) understanding the mechanism of reactions following C-C cleavage, B) developing a predictive model of cleavage rate as a function of temperature and force and C) understanding the synergistic interplay of catalytic spheres and mechano-chemical activation. To achieve this, I will develop a new methodology for in-situ spectroscopy during ball milling in combination with radical trapping and apply the tunable direct mechano-catalysts to a variety of polymers.

Mots-clés : mechano chemistry,mechano catalysis,depolymerization,chemical recycling,ball milling
Projet ERC : DistantDust (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
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 : 1499643.9 €

At the core of galaxy evolution is the evolution of the baryonic components that modify the observable properties of galaxies. A crucial component of the baryonic matter is the interstellar medium (ISM) that consists of gas and solid-phase metals called dust. Interstellar dust determines how galaxies look like from UV to IR, how the ISM behaves, and the very process of star formation that creates the stellar component that defines a galaxy. Despite our wealth of knowledge about dust in local galaxies, very little is known about the properties of dust grains, where it resides inside galaxies, and how it is formed, beyond the nearby Universe (i.e., at high redshifts). The fundamental importance of advancing our knowledge about dust at high redshifts is further underlined by the vital need to correct for its attenuation effects in the observed rest-frame UV/optical emission of high-redshift galaxies. This situation will fundamentally change in the next few years owing to the unprecedented capabilities of the James Webb Space Telescope (JWST). This ERC program capitalizes on the massive technological advance of JWST to take a holistic approach, physically and observationally, and conduct a panchromatic study of dust emission and absorption properties at two key cosmic epochs:1) z~1-3, dubbed as Cosmic Noon, the peak epoch of cosmic star formation activity, and 2) z~5-10, the early Universe and the epoch of reionization. Owing to my leading role in multiple deep extragalactic JWST surveys, my ERC group will take full advantage of the very first data from this revolutionary observatory. This will be done in synergy with ALMA and other powerful ground-based observatories such as VLT and Keck to observe the attenuation and emission properties of dust from rest-frame UV to submm wavelengths at Cosmic Noon and beyond. This ambitious research program will bring novel key insight into the physical processes that enable star formation and galaxy evolution throughout cosmic time.
Projet ERC : 3DVasCMD (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
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 : 1496395.0 €

Coronary microvascular disease (CMD) is a significant healthcare challenge, contributing to ischemic heart disease, the number one global cause of human mortality. CMD is associated with dysfunction of small coronary vessels, due to ageing, obesity and metabolic disease, that reduces blood flow and oxygenation in the heart. Despite its widespread impact on health, our understanding is limited to animal studies, which do not recapitulate the pathophysiology in humans, nor can they be used to reveal cellular crosstalk in a controlled manner. Thus, there is a critical need to develop a humanized in vitro model to mimic CMD. Advances in organ-on-chip and induced pluripotent stem cell (iPSC) technologies, together with our state-of-the-art 3D humanized vascular models, provide new opportunities to investigate CMD. 3DVasCMD builds on our expertise to develop a complex vascularized cardiac model, to reveal pathological mechanisms and novel therapeutic targets of CMD. By combining cutting-edge tissue-engineering approaches we will: 1) Develop and characterize a 3D vascularized cardiac model, 2) Determine the impact of known risk factors on the pathophysiology of CMD; 3) Develop a high-throughput system for cardiovascular drug screening. Our model will reveal cardiac tissue-vessel crosstalk by combining autologously-differentiated iPSCs in a controlled fluidic environment. This model will enable unprecedented study of ischemia, diabetes, and sex-hormone contributions to CMD using 3D in vitro tissues. Ultimately, a high-throughput version of our model, combined with machine learning, will predict the efficacy of therapeutic targets.  Using an interdisciplinary approach, 3DVasCMD will impact our understanding of how microenvironmental and heritable risk-factors contribute to CMD. This model has the potential to study multiple facets of vascular disease and can be further developed into a preclinical tool, which will be a breakthrough for cardiovascular biology and medicine.

Mots-clés : vascularized in vitro cardiac model,high throughput drug screens
Projet ERC : GutTransForm (Horizon Europe, appel 2022, 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 : 1894858.75 €

The variability of the human gut microbiome (entirety of microorganisms inhabiting the intestine) far exceeds human genome variability, and has been connected to various aspects of human health. Although microbiome differences are often linked to altered metabolism, the current view on metabolic interactions between the microbiota and the host remain mostly descriptive due to several limiting factors. First, most sequencing-based human microbiome studies rely on correlative analyses between microbiome composition and human phenotypes, depend on largely incomplete microbial genome annotations, and are not targeted to identify community-mediated functional traits. Second, many metabolites can be both of microbial and human origin, which makes it conceptually and methodologically challenging to disentangle metabolic microbiota-host interactions. To overcome these limitations, I propose a systematic bottom-up strategy to mechanistically study metabolic microbiota-host interactions by harnessing gut microbiota’s capacity to biotransform (chemically modify) drug molecules. The large chemical diversity and exogenous origin makes medical drugs ideally suited for experimental in vitro and in vivo approaches to probe microbiota-host interactions in a controlled way. We will combine high-throughput culturing protocols, genetics, metabolomics measurements, genomics analyses, gnotobiotic mouse work, and computational modeling to connect interpersonal differences in microbiome composition to differences in metabolic functions of individuals’ gut microbiota, and ultimately link them to molecular host phenotypes. Generating these mechanistic insights and transformational resources is essential to understand the fundamental principles of the microbiota-host relationship. In addition, this project has direct medical relevance, as it provides actionable microbiome-based links to interpersonal differences in medical drug response, which remain a widespread problem in clinical practice.

Mots-clés : microbiome,bacteriology,metabolism,gnotobiotic mouse models,drugs
Projet ERC : TIMERR (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Life Science
Panel : Cell Biology, Development, Stem Cells and R egeneration
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 : 1648555.0 €

Reproducibility in development is maintained via precisely-timed execution of gene regulatory programs required to build all cell types of the embryo. However, many perturbations challenge this robustness and accelerate developmental tempo, leading to increased phenotypic variability. Mechanisms underlying this century-old observation have been obscured by variation inherent to embryogenesis, but advances in statistical single-cell profiling have revealed an unappreciated source of variability: non-uniform progression of development across cell types. Here, I propose to use a combination of ultra-scalable single-cell genomics, cross-species alignment of developmental trajectories, and engineering of developmental rate to understand how cell type-specific timing differences influence reproducibility of development. First, comparing vertebrate species with natural tempo differences, fast-developing zebrafish (Danio rerio) and slow-developing medaka (Oryzias latipes), we aim to generate time-resolved single-cell transcriptomic profiles and map variation in cell type-specific timing. We will relate timing variation to a quantitative robustness measure derived from cell composition profiles for hundreds of embryos, asking how the tempo of development influences its ability to reproducibly build a well-proportioned animal. Second, we aim to identify cell type-specific drivers of timing and coordination. Specifically, we will modulate tempo embryo-wide and test for proportional timing changes across cells by tracking responses to perturbation at the cell type level. We will then use genetic tools to promote lineage-specific acceleration of development, assessing the embryo’s capacity to compensate for an induced asynchrony. In challenging coordinated developmental progression in evolutionary, perturbation, and synthetic contexts, we will resolve how timing impacts reproducibility in development.

Mots-clés : developmental robustness,developmental timing
Projet ERC : FRESH-CARE (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth System Science
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 : 1499482.0 €

The Arctic is warming rapidly, causing significant hydrographic changes including sea ice retreat, freshwater accumulation, and altered ocean currents. These changes intensify water stratification potentially destabilizing Earth's thermohaline circulation. Despite its key role in global climate system, the ultimate fate of Arctic freshwater remains unconstrained. Current estimates lack the resolution that remote sensing and Artificial Intelligence (AI) can provide. It is crucial to improve freshwater flux uncertainties, to better constrain future projections and understand global climate impacts.   FRESH-CARE aims to transform our understanding of Arctic freshwater dynamics. It will develop innovative methodologies that leverage (radiometric, thermal, and altimetric) satellite data, AI-integrate remote sensing and in-situ information, and run model simulations to forecast freshwater transports under various Shared Socioeconomic Pathways. FRESH-CARE will focus on three specific objectives: (1) develop a novel AI-based methodology to characterize four-dimensional ocean currents; (2) quantify freshwater transports through the main Arctic gateways; and (3) perform simulations for future Arctic freshwater scenarios using a coupled ice–ocean model.    Overall, I envision that FRESH-CARE will offer a multidisciplinary view of ocean currents and freshwater fluxes in the Arctic Ocean over three decades, from hindcast in the 2010s to forecasts into the 2040s. FRESH-CARE will provide pan-Arctic estimates of ocean currents and freshwater distribution with high spatiotemporal resolution, benefiting polar oceanographers, earth modelers, and climate scientists, as well as to the society at large. FRESH-CARE findings will enhance the understanding and assimilation of ocean freshwater in future global climate models.

Mots-clés : arctic oceanography freshwater ocean current remote sensing
Projet ERC : Mut-Scales (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Conseil supérieur de la recherche scientifique — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 991010.0 €

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

Mots-clés : mutation,germline,dna damage and repair,primates
Projet ERC : OBESE-EMBRYO (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
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 : 1499998.0 €

>50% of all pregnancies occur in couples with overweight or obesity, leading to tremendous risks for pregnancy and long-term offspring cardiovascular complications. My hypothesis is that an embryonic obesogenic environment, induced by the mother and father-to-be, predisposes to placental and embryonic programming of cardiovascular diseases across the life course. This leads to the intergenerational cycle of the cardiovascular disease epidemic. Lifestyle interventions in pregnancy are emerging, but unsuccessful in improving pregnancy or offspring cardiovascular outcomes due to inadequate timing, unclear intervention targets and unpredictable outcomes. OBESE-EMBRYO aims to radically improve care for overweight and obese parents-to-be by targeting the embryonic obesogenic environment to prevent development of cardiovascular diseases in offspring. To fulfil this mission, OBESE-EMBRYO will provide crucial insights for evidence-based, personalized, prevention and intervention strategies from preconception onwards. Beyond state-of-the-art aspects: 1) First population-based study on preconception and early-pregnancy as critical periods for adverse effects of an embryonic obesogenic environment, induced by the mother and father-to-be; 2) Intergenerational metabolism studies using metabolomics and oral-glucose-tolerance-tests to identify unknown metabolic pathways; 3) Cutting-edge imaging studies of cardiovascular development from embryonic life into adulthood to identify unknown developmental adaptations; 4) Longitudinal, repeated, placental-miRNA-studies throughout the first trimester, with an integrated approach to address replication, tissue specificity, functionality; 5) Translation of results into prediction models for offspring cardiovascular complications using Artificial-Intelligence and an evidence-based clinical support system for overweight and obese parents-to-be. Expected results will have great population impact on cardiovascular health in future generations.

Mots-clés : maternal and paternal obesity pregnancy developmental programming of cardiovascular diseases
Projet ERC : OncoNichPath (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Université Paris Cité — Pays : France — Rôle : PI
Acronyme de l'entité : UP Cité
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1911428.0 €

Although oncogenic driver mutations are found in healthy tissues sometimes at a prenatal stage, they do not often result in overt cancer. This genotype – phenotype discrepancy warrens the search for extrinsic mechanisms of cancer development and maintenance, such as aging or exposition to specific environments. Using myeloid neoplasms as a cancer model, I aim here at dissecting the hematopoietic-niche partnership at the “pre-leukemic”, “leukemic” and “post-leukemic” stage to identify innovative therapeutic strategies to prevent acute myeloid leukemia (AML) development, maintenance and recurrence. To enable experimental modelling of the bone marrow niche at different disease stages, I collected longitudinal paired stromal and hematopoietic primary patient samples, and generated physiologically-relevant in vitro and in vivo humanized models. In this proposal, I will first apply large-scale pooled genetic screening approaches to gain insights into the role of the hematopoietic-niche cellular communication processes in leukemic transformation of “pre-leukemic” clonal myeloid conditions. In the second part of the proposal, I will combine cutting-edge spatial single-cell RNA sequencing technologies with functional genetic screening to dissect the “leukemic-niche” crosstalk and ultimately fuel the development of concomitant “seeds” and “soil” therapeutic strategies. Finally, I will design a functional single-cell screening approach allowing modulation of the “post-leukemic” niche, to open the road for novel maintenance treatment strategies re-establishing healthy hematopoietic stem cells fitness advantage to prevent relapse.  Overall, the proposed research project provides a framework for defining and understanding the dynamic influence of the hematopoietic niche as an oncogenic path to myeloid neoplasms evolution, and represents a key step towards therapeutic niche reprogramming from a “malignant” to a “healthy” state, to improve cancer patients’ prognosis.

Mots-clés : myeloid neoplasms,acute myeloid leukemia,bone marrow microenvironment,tumor stroma crosstalk,therapeutic targets,preventive and curative therapeutic strategies,prognosis biomarkers,humanized models,single cell transcriptomics,large scale genetic screens