Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MadSilica (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth System Science
Entité participante : Université de Stockholm — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999780.0 €

Over its long geological history, the overall habitability of Earth has been governed by the chemical alteration of silicate minerals, a reaction that buffers pCO2 and climate. While terrestrial silicate weathering is widely appreciated, marine silicate weathering and reverse weathering (or marine silicate alteration, MSiA, altogether), has long been considered insignificant in the big picture. This paradigm is challenged by recent work that suggests reverse weathering, as an oceanic Si sink, could be three times higher than previously thought. The latest estimates of marine silicate weathering showing its CO2-fixing capacity could be 82% of that of its terrestrial counterpart. Though potentially significant, these estimates are associated with large uncertainties and untested assumptions. In particular, information about the exact chemical pathway of MSiA, kinetics, and the environmental dependency is missing. To fill these gaps, I will provide the first comprehensive assessment of MSiA by quantifying its rates through both laboratory experiments and field observations. While the former constrains how MSiA initiates, the latter represents the million-year quasi-steady state condition in nature. Reproducing the conditions for MSiA in the laboratory is undeniably challenging due to the required multi-year incubation under up to 340 times atmospheric pressure and near-frozen conditions, which I can reproduce with a novel apparatus. Circulation of modified seawater with realistically slow flow will be maintained to derive MSiA rates through continuous fluid composition monitoring. Together with the rates estimated from field observations, I will evaluate the dependency of MSiA on environmental factors, such as the type/quality of silicates and organic matter. The project will be transformative in our understanding of the coupling between Si and C cycles, and thus provide fundamental knowledge for predicting Earth responses to a likely hotter and wetter future.

Mots-clés : silicate diagenesis,sediment incubation,co2 fixation,weathering,reverse weathering
Projet ERC : MAGHEAT (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
Entité participante : Université de Stockholm — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1994937.5 €

The mechanisms that heat the solar chromosphere and corona, and that drive the solar dynamo, arguably remain some of the foremost questions in solar and stellar physics. Here, we focus on the question of how energy is transported and released in the solar chromosphere. During the past 20 years, numerical simulations of the chromosphere have been used, with increasing degree of sophistication, to validate various proposed heating mechanisms. These studies have gradually come to recognise that the mechanisms that are likely dominant may be different in different parts of chromospheric fine structures. To make progress, we therefore need constraints from highly resolved observational data.  Recently, I implemented an inversion code that allows estimates of the overall chromospheric heating from spatially and spectrally resolved observational maps. Our results have unveiled very finely structured heating distributions with much larger amplitudes than the hitherto assumed canonical values. But a limitation is that this implementation cannot directly discriminate between the different heating mechanisms that have been proposed.  The goal of MAGHEAT is to identify what mechanisms are heating the chromosphere, characterize the energy flux that is being released into the chromosphere and separate the contribution from each mechanism in active regions and flares. This goal is achievable with the combination of the proposed development of novel non-LTE inversion methods, new hybrid rMHD/particle simulations, and the availability of datasets with unprecedented high spatial resolution, large field-of-view, and high S/N ratio from DKIST, the Sunrise III mission, NASA’s IRIS satellite and updated instrumentation at the Swedish 1-m Solar Telescope. We will use observational data from these facilities to reconstruct new 3D empirical models of the photosphere and chromosphere, which will allow us to identify the mechanisms that are responsible for the energy deposition.

Mots-clés : nlte radiative transfer,chromospheres,nlte inversion methods
Projet ERC : NanoCat (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Materials Engineering
Entité participante : Société Max-Planck pour le développement des sciences — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : Société Max Planck
Type d'entité : Recherche
Financement ERC de l'entité : 83750.0 €

All life is dependent on enzymatic reactions and functional enzyme cascades have been evolutionary optimized. Yet, introducing “foreign” enzymes into other organisms through genetic engineering often results in reduced or no enzymatic activity. In nature enzymatic activity and efficiency are often enhanced by encapsulation of enzymes in microcompartments resulting in protection and rate enhancement through high local concentrations of enzymes, co-factors and substrates. In NanoCat I will engineer artificial microcompartments hosting highly efficient enzyme cascades that are operational in organisms where they do not naturally occur. The approach is based on my recently developed method to controllably template silica nanostructures by DNA origami. These inorganic materials retain the attractive features of DNA origami like precise localization and number placement of proteins of interest. Combining the power of DNA nanotechnology with the sturdiness and biocompatibility of silica as artificial enzyme-hosting microcompartments, I now have a highly disruptive tool at hand that has the power to outperform standard biological methods and be a true game changer. NanoCat is a novel approach to assemble complex enzymes outside of their natural environments to address health issues, global carbon emissions and plant fertilizers, something that current biological methods struggle to do. The immense demand in today’s agricultural, climate and health needs urgently calls for engineered systems with full control over size, shape and functionalizability to enhance enzymatic activity and endow organisms with new and improved properties. NanoCat aims to provide a solution to these issues through the assembly of artificial enzyme-hosting microcompartments from silicified DNA origami with universal applicability, which I will exemplify through the formation of “carboxy-, nitrogy- and galactysomes” for CO2/nitrogen fixation and the cellular delivery of essential lysosomal enzymes.

Mots-clés : dna origami,enzyme cascades,silica
Projet ERC : FLEXBRAIN (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : Société Max-Planck pour le développement des sciences — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : Société Max Planck
Type d'entité : Recherche
Financement ERC de l'entité : 1409437.5 €

The human brain is flexible. Neural networks adapt to cognitive demands by flexibly recruiting different regions and connections. Flexible network adaptation enables cognitive functions such as semantic cognition: the ability to use, manipulate, and generalize knowledge. When key nodes suffer damage, networks can adapt to recover function. Yet, brain lesions often severely impair semantic cognition. How the semantic network adapts to lesions is poorly understood. My hypothesis is that disruption of the semantic network can be compensated for by recruitment of domain-general networks. This notion is based on findings that disruption of semantic nodes inhibits semantic activity but increases activity in domain-general nodes. Yet, the behavioral relevance of domain-general recruitment is unclear. Compensation means that behavior can be preserved as other nodes work harder. Can domain-general networks effectively compensate for disruption of specialized nodes? Is this a common principle of flexible adaptation in the healthy young, aging, and lesioned brain? Unprecedented inhibitory and facilitatory neurostimulation will be used to unbalance and rebalance network adaptation in semantic cognition. Importantly, a novel network stimulation approach will target multiple nodes simultaneously. I ask three questions. (i) Can domain-general networks compensate for semantic network disruption? (ii) Is domain-general recruitment in the aging brain adaptive? (iii) Do domain-general networks drive flexible adaptation to lesions? Perturbing young brains will elucidate the relevance of network adaptation. Perturbing aging brains will probe compensatory reorganization. Facilitating lesioned brains will reshape flexible adaptation. Benefitting from my strong neurostimulation experience, we will elucidate the way the brain compensates for disruption. The potential impact of the project on current conceptions of brain plasticity, and for rehabilitative medicine in particular, is immense.

Mots-clés : semantic cognition,neurostimulation,functional neuroimaging,compensation
Projet ERC : ORGANise-T (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Leibniz-Gemeinschaft — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : WLG
Type d'entité : Recherche
Financement ERC de l'entité : 1997943.0 €

T helper cells represent a heterogeneous population of immune cells that are critical for host defense and, if dysregulated, for pathologies such as autoimmunity and allergy. T cell responses take place in peripheral tissues. Yet, insights into their identity and regulation stem almost exclusively from investigations of circulating blood, which comprises only 2% of the total human T cell population. Accordingly, current immunomodulatory drugs act systemically, but lack tissue specificity. Despite progress in the temporary suppression of chronic inflammatory diseases, they still fail to be curative. This project aims to address this unmet medical need by generating fundamental insights into the dynamic compartmentalisation of human tissue resident T helper cells across space and time. I have established a surgical patient cohort for the collection of multi-organ tissue samples and a cohort of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) that enables tracking T cell tissue entry and exit over time in matched organs by single-cell chimerism analysis. Using multimodal state-of-the-art technologies and specialised high-throughput cell culture methodologies in these two unique patient cohorts, the project will dissect 1) the phenotypic, functional and transcriptional identity and molecular regulation of human resident T helper cells across tissues, 2) the compartmentalisation of their antigen specificities across tissues, 3) the dynamics of tissue entry, persistence and exit for distinct T helper cell types in space and time, and will then 4) exploit chimeric host/donor T cell-tracking to gain novel insights into the cellular and molecular pathways underlying graft-versus-host disease. Overall, ORGANise-T will establish first-of-its-kind insights into the spatio-temporal dynamic organisation of human T cell immunity in tissues. This will bring the next generation of immunotherapies to the level of tissue specificity.

Mots-clés : t helper cells,tissue resident t cells
Projet ERC : DREAM-SWIM (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
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 : 2130686.0 €

Electron microscopy (EM) has played a key role in the discovery of many new materials, as well as the elucidation of the role of defect structures and interfaces on material properties and behaviour. Current electron microscopes are capable of maintaining the relevant hydrated state of samples by means of cryofixation techniques or by using dedicated liquid cells. This opens up the possibility of investigating crucial interfaces, such as those in complex aqueous systems that, despite their significance, remain poorly understood. The study of water-solid interfaces in the EM is currently limited by the sensitivity of aqueous samples and interfaces to the action of the electron beam. Knowledge of the fundamental chemical processes induced by interaction with the electron beam is needed for the interpretation of results, prediction and design of experiments and to potentially mitigate electron-beam effects. Here, I propose to develop novel instrumentation and approaches to allow for the direct determination of the yields of radicals and molecules produced as well as reaction kinetics in the EM and at the interface between materials and aqueous solutions. This new concept will permit us to precisely assess the effect of important factors in the radiolysis of aqueous solutions inside the EM such as the very high electron dose rates, the supports, liquid volume, temperature or the effect of nanomaterials’ interfaces. This newly accessible knowledge will lead to the interpretation of numerous EM experiments and will be used to develop novel data-informed adaptive scanning approaches specifically designed for in situ dynamic acquisition with minimal chemical effects in the samples. An important goal of this project is to conceive new predictive models for the radiolytic chemistry produced during EM experiments, which will open the door to the future design of mitigation procedures for radiolysis damage in EM.

Mots-clés : radiation damage,liquid cell electron microscopy,liquid phase electron microscopy,cryo eels
Projet ERC : ROGALLO (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
Entité participante : Université Charles de Prague — Pays : Rép. Tchèque — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2310044.0 €

This project aims to conduct previously unachievable (magneto)hydrodynamical simulations of binary systems involving stars, planets, neutron stars, and black holes. The phenomena occurring in these systems lie at the heart of some of the most important unsolved astrophysical problems, such as the evolutionary origin of gravitational wave sources, the acceleration sites of high-energy particles, and the coevolution of galaxies with their supermassive black holes. Advancements in the theoretical understanding of these phenomena are urgently needed to interpret observations from a wide range of current and future ground- and space-based facilities. Traditionally, numerical simulations of fluid dynamics in binary systems have relied on general-purpose codes that either discretize matter into particles or divide space into finite volume elements organized in an unstructured or logically-Cartesian mesh, such as spherical or cylindrical coordinates. However, these approaches lose accuracy or yield unphysical results when applied to the complicated, yet largely predictable, structure of binary systems. To achieve a dramatically higher level of realism in fluid dynamics simulations of binary systems, I will develop a new 3D parallel multiphysics code, ROGALLO. This code will be based on the discontinuous Galerkin method coupled with complex meshes specifically adapted to structures arising in binary systems. Leveraging the most recent developments in numerical mathematics, I will use ROGALLO to substantially advance the theory of fundamental processes such as pulsations, turbulence, mixing, mass transfer and mass loss, accretion, and explosions for a wide variety of binary systems. These systems include tidally-deformed or mass-transferring stars, chemically-homogeneous gravitational wave progenitors, classical novae, Type Ia supernovae, circumbinary disks around supermassive black holes, or gaseous bodies moving through fluid.

Mots-clés : binary stars,binary black holes,mass transfer and loss,pulsations,explosions,circumbinary disks,classical novae,magneto hydrodynamics,numerical methods
Projet ERC : LIFE-19 (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : Université Charles de Prague — Pays : Rép. Tchèque — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2498875.0 €

This proposal aims to construct a bacterial strain LIFE-19 which relies solely on 19 amino acids to build all its proteins. While all living cells known to human beings produce proteins from the same 20 coded amino acids, the study of origins of life imply that earlier cells may have functioned with a smaller alphabet. This is thought-provoking in the present biological context, wherein each of the 20 serves a distinct and vital role. Although many scientists have engaged in theoretical exercises involving the reduction of this amino acid “alphabet”, the inherent biological intricacy and a lack of suitable tools have impeded experiments on an organismal level. This project seeks to mutate all the tryptophan (Trp) protein sites in a minimal Mycoplasma genome template. Trp stands out as both one of the scarcest and one of the evolutionary youngest members of the protein alphabet. Here, we will engineer Trp out of a minimal genome in a 2-stage process. Initially, semi-automated gene editing will target all individual Mycoplasma Trp-sites concurrently, using broad randomization schemes (capitalizing on the PI’s expertise). This will allow us to compare Trp dispensability across the proteome and select the most viable Trp-substituted protein variants. Second, the selected mutations will be combined to “write” a new LIFE-19 genome using a bottom-up synthesis. LIFE-19 will lay the next steppingstone to our understanding of life’s limits. We will be able to get a glimpse into what cells probably went through billions of years ago, when they teetered on the border between life and nonlife. With the reduced number of building blocks, LIFE-19 will also generate an important step towards a cellular chassis with minimal energetic demands and therefore key inventory in Synthetic Biology research. Overall, this project will challenge the textbook knowledge that life depends on the 20 canonical amino acids, by effectively UNalphabeting the Central Dogma of biology.

Mots-clés : minimal cell,laboratory evolution,genome editing,genetic code evolution,origins of life
Projet ERC : SENTINEL (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
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 : 2000000.0 €

Metabolic and immune pathways form an intricate network that maintains homeostasis. We recently unveiled that the Stimulator of Interferon Genes (STING), central to triggering cytosolic dsDNA-dependent type I Interferon (IFN) responses, inhibits the desaturation of essential dietary polyunsaturated fatty acids (PUFAs). STING thereby controls the generation of long-chain PUFAs (LC-PUFAs) that in turn inhibit STING activation. This double negative regulatory feedback loop operates as a key rheostat of homeostasis. Interestingly, we found that metabolic tissues, such adipose tissues, express low levels of STING, and that in vitro adipocyte differentiation leads to STING downregulation, although they retain their ability to produce type I IFNs in respond to nucleic acid challenge. This suggests that alleviating the STING-dependent inhibition of PUFA metabolism may result from, or be required for, adipocyte differentiation or functionality. Further, this also suggests that adipocytes may possess specific STING-independent cytosolic nucleic acid detection pathways. Thus, nucleic acid detection pathways and PUFA metabolism should be interrogated concertedly, at the cellular levels, within metabolic tissues, to uncover how they define tissue-specific immune responses and regulate tissue homeostasis, in particular in pathologies presenting with chronic STING activation. Within SENTINEL, we will combine state-of-the art biochemistry and molecular biology approaches, and cutting-edge omics tools, in vitro and in vivo to identify nucleic acid detection machineries and question the role of STING downregulation in metabolic cells. Finally, we will explore the impact of STING-dependent metabolic alterations in pathologies presenting with chronic STING activation. SENTINEL will thus chart an unexplored area of nucleic acid immunity (metabolic cell immunity), and reveal its impact on homeostasis and pathologies.

Mots-clés : inflammation nucleic acid immunity polyunsaturated fatty acids oxylipins type i interferonopathies adipose tissue adipocytes sting fads2 type i interferons
Projet ERC : Dynamyelo (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
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 : 1249839.0 €

Although changes in immune blood cell number is commonly used as a sign of infection or inflammation in the clinics, the cell dynamics parameters controlling cell numbers during an immune response (division, differentiation, and death) are not well understood. As myeloid cells are short lived, changes in myeloid cell numbers comes from cell production by myelopoiesis. Given the importance of cell dynamics in immune response, we propose to unravel the cell dynamics of myelopoiesis during inflammation. However, few methods allow to measure in vivo the cell dynamics parameters. Methods to study division in vivo can trace up 10 divisions, apart for the telomere measures that have no maximum but is restricted to cell types without telomerase activity, unlike our cells of interest. As we estimate a minimum of 14 divisions from hematopoietic stem cells to myeloid cells, a new method to follow over 10 divisions is required. This proposal will overcome this methodological barrier by developing the DivCounter a new method, to count division in vivo in mice. Our innovation is: 1/ to implement a quantitative counter of division combining wet and dry lab. 2/ compatible with single cell transcriptomics to measure cell differentiation status with the required granularity. 3/ creating a new mouse model. Using the DivCounter, we will quantify for the first time the number of divisions in homeostatic myelopoiesis. We will also infer division, differentiation and death rate, uncovering the understudied role of death in myelopoiesis. We will also unravel how division and death change during emergency myelopoiesis and when and how myelopoiesis returns to homeostasis after inflammatory stimulations. This knowledge will shed light on which of the cell dynamics parameters to intervene to change myeloid cell numbers, opening therapeutic perspective for the design of vaccines and immunotherapies. The DivCounter will serve other fields in which cell dynamics is key (cancer, development).

Mots-clés : division,emergency myelopoiesis,mathematical model,cell dynamics