Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet SCRIBE (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Although multiple regulatory layers have been reported to control stem cell differentiation, including epigenetics, cell signaling and metabolism, we still lack sufficient knowledge on how differentiation processes are connected and coordinated. The Hentze laboratory recently discovered that RNA modulates (riboregulates) the activity of the glycolytic enzyme Enolase 1 (ENO1) and that this interaction is essential for in vitro murine embryonic stem cell differentiation. Additionally, unpublished data from the laboratory show that the glycolytic enzyme pyruvate kinase (PKM) is also riboregulated. However, the role of riboregulation during primary stem cell differentiation remains elusive. Previously, RNA-bound proteomes have either been identified in cultured cells or ex vivo in whole organs. I aim to investigate enzyme-RNA interactions in primary stem cells and differentiated progeny, using the hematopoietic system as a model. First, I will analyze the RNA-binding activity of previously in cellulo profiled enzymes ENO1 and PKM in vivo and ex vivo during hematopoietic stem cell (HSC) differentiation by RNA-proximity ligation assays, profiling of stem cell activity and transcriptome analysis (aim 1). Secondly, I will analyze, identify and comparatively quantify global RNA-protein interactions in HSCs, progenitors and mature blood cells by developing a method to profile in vivo RNA-protein interactions (aim 2). In an interdisciplinary approach, I will pair fluorescence-activated cell sorting with state-of-the-art RNA-protein cross-linking approaches and ultra-low input proteomics analysis. The generated data will help, for the first time, to understand at the analytical and functional level whether and to what degree riboregulation of enzymes represents a regulatory paradigm operational in mammalian cells, with a focus on hematopoietic stem cell differentiation.

Mots clés : rna biology, rna protein interaction, riboregulation, metabolism, glycolysis, stem cell, differentiation, cancer

Participants :
- Laboratoire européen de biologie moléculaire (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 189687.36 €
Projet BiPMeM (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The human gut microbiota, the trillions of microbes inhabiting our gastrointestinal tract, encodes an enormous number of metabolic enzymes, responsible for diverse biochemical reactions that determine metabolic microbiota-host interactions. Bacterial biotransformation reactions, the chemical modification of compounds by bacteria, seem to play a central role in such metabolic interplay between the gut microbiota and its human host. A number of gut microbial biotransformations such as reductive and hydrolytic reactions, as well as their metabolic enzymes, have been recently described. The natural roles of these biotransformation pathways in bacterial metabolism and their influence on host physiology have been associated with gut bacterial fitness, nutrition uptake, immune signaling, as well as personal drug response and toxicity. Despite these important functions, our mechanistic and physiological understanding remains still limited for many gut microbial biotransformation reactions, such as chemical conjugation. To fill this knowledge gap, I present a multidisciplinary plan to systematically investigate conjugative biotransformation reactions of gut bacteria. I will develop mass spectrometry-based methods to identify gut bacterial species and strains that perform conjugative biotransformations, employ high-throughput gut bacterial genetics to identify the responsible genes, determine their role in bacterial metabolism, and eventually assess selected examples for their impact on microbiota-host interactions in gnotobiotic mouse models. If successful, this project will provide novel insights into gut microbial metabolism, and pave new ways to develop strategies for the rational manipulation of gut microbial community functions for better health outcomes. Furthermore, this project will expand my professional network, transferrable skills, and scientific competencies, thus providing me the greatest opportunity to mature towards an independent scientist and investigator.

Mots clés : human gut microbiota microbial biotransformation mass spectrometry metabolomics anaerobic microbiology gnotobiotic mouse models

Participants :
- Laboratoire européen de biologie moléculaire (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 173847.36 €
Projet S-FOX (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

The main goal of this project is the development of new polymeric catalysts and new catalytic membranes, designed to carry out high-end chemical oxidation in aqueous streams. Catalytic membranes are means to perform chemical transformation at the solid/ fluid interface and they are ideal interfacial reactors and contactors, simultaneously catalyzing and directing the heterogeneous phase reaction between substrates and oxidant agents. These systems have a key role in the future process industry and in water treatment since they enable oxidation reactions whilst reducing reagents and waste. Current systems employ inorganic and often high-value catalysts, which are generally of high cost, and prone to leaching causing loss of performance in time. I propose the first fully polymeric catalytic membrane made exclusively of bio-inspired iron coordination polymers. This research will lead to key scientific breakthroughs by: i) creating new non-heme catalytic polymers that mimic the activity of biological enzymes and that can be efficiently deployed to cast membranes for heterogeneous reaction; ii) designing and fabricating polymeric membranes consisting of the catalytic macromolecules and with suitable surface and morphological properties to precisely guide and enhance the contact among the reagents and with the catalyst; iii) successfully applying these systems maintaining high catalytic rate and yield and to understand the mechanisms and pathways of transformation of compounds, especially water micropollutants. These innovations will enable membrane robustness, long-term efficiency, and low cost. In particular, the potential of the new catalysts, membranes, and membrane reactors will be exemplified in the purification of contaminated streams to produce safe water. Thus, this new system represents a platform for a plethora of further advances in the field of oxidation processes applied to chemistry, engineering, and the environment.

Mots clés : catalytic membrane, advanced oxidation process, contaminants of emerging concern, polymeric non heme catalysts

Participants :
- Université de Montpellier (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195914.88 €
Projet VEAT-ChiP (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Obesity-associated metabolic and cardiovascular diseases (CVDs) are serious public health concerns. A fat depot surrounding the heart, known as epicardial adipose tissue (EAT), is likely contributing to the pathologic conditions leading to CVDs. But it might also play a protective role during ischaemic events highlighting a complex role of EAT in heart homeostasis and disease. Some studies report post-menopausal women having an increased EAT suggesting that changes in levels of of sex hormones affect EAT and may cause sex-specific contributions to metabolic diseases. Though EAT covers nearly 80% of a human heart, it is virtually absent in rodents. Given the underexplored role of EAT in the pathology of CVDs, and the lack of animal models, human in vitro cardiovascular EAT model is necessary. VEAT-chip proposes to develop the first human induced pluripotent stem cells (hiPSCs) derived, fully autologous, vascularized EAT-on-chip model. The project will start with establishing a novel protocol to obtain epicardial adipocytes. Then, those cells will be integrated into hiPSCs derived cardiac-specific vessels-on-chip to generate a vascularized EAT-on-chip. Given an undetermined role of sex hormones for EAT function and an unclear balance of protective and toxic effects of EAT in pathological settings, vEAT-chip will explore hormone- induced changes in function of EAT during homeostasis and stressed conditions. In a final aim of the project, addition of cardiomyocytes (CMs) to the system will result in a model resembling a portion of the heart wall. By combining novel hiPSCs differentiation protocols, organ-on-a-chip technologies, advanced microscopy techniques, and global transcriptome and secretome analysis, the VEAT-chip project will reveal EAT-associated factors affecting healthy function of cardiac-specific vessels and CMs. Ultimately, VEAT-chip will provide a novel means to study cellular crosstalk and unravel mechanisms associated with cardiometabolic diseases.

Mots clés : organ on a chip, epicardial adipose tissue, human induced pluripotent stem cells, vascularised in vitro tissues, sex hormones

Participants :
- Laboratoire européen de biologie moléculaire (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 194074.56 €
Projet SpliceTomo (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The spliceosome is a dynamic, multicomponent macromolecular complex essential for the precise removal of introns from pre-mRNA. While extensive genetical, biochemical, and structural studies have provided insights into the splicing cycle, the structural dynamics and distribution of spliceosomes within human cells remain only partially understood. In this project, I aim to study the in situ structures of the spliceosome by cryo-electron tomography (cryo-ET) and sub-tomogram averaging, alongside other advanced techniques, to elucidate the dynamic assembly and spatiotemporal distribution of spliceosome, as well as its crosstalks with other nuclear machinery. This research aims to visualize macromolecular complexes in their native environments at near-atomic resolution in the nucleus, providing new insights into the mechanisms of pre-mRNA splicing in human cells.

Mots clés : spliceosome cryo electron tomography in situ structural analysis dynamic assembly

Participants :
- Laboratoire européen de biologie moléculaire (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 242260.56 €
Projet SPiN (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The "Splicing Processes in Nucleomorphs" (SPiN) project leverages the unique properties of nucleomorphs to explore in situ the nuclear architecture and gene expression at an unprecedented level. Using cutting-edge cryogenic electron microscopy (cryo-EM) techniques such as tomography, subtomogram averaging and single particle analysis, I want to provide novel understanding of how pre-mRNA splicing happens in the context of genome reduction. I will overcome the limitations of current cryo-ET studies of the nucleus that struggle with the large size and dense environment of typical eukaryotic nuclei. Nucleomorphs, with their small size, enable a more accessible and efficient approach to in situ studies, bypassing the need for complex sample preparation steps.  The SPiN project is structured around three specific aims: (1) isolating intact nucleomorphs for comprehensive proteomics and transcriptomics and structural analysis, (2) purifying and structurally characterizing spliceosome complexes unique to nucleomorphs, and (3) visualizing the structural landscape of nucleomorphs to understand the spatial organization of gene expression targeting spliceosome structures for in situ structural determination. By establishing nucleomorphs as a powerful model for in situ studies, this project promises to uncover new insights into pre-mRNA splicing mechanisms and nuclear organization, with far-reaching implications across evolutionary biology, cell biology, and biotechnology. The potential for groundbreaking discoveries positions nucleomorphs as a transformative tool to advance our understanding of eukaryotic genome evolution and the mechanisms underlying nuclear processes.

Mots clés : pre mrna splicing, spliceosome, nucleomorph, in situ, gene expression, cryo electron tomography, proteome

Participants :
- Laboratoire européen de biologie moléculaire (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 242260.56 €
Projet RESTORE (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Nosocomial pneumonia is the second most common and most frequently fatal hospital-acquired infection worldwide. Previous understanding of lung health depicted a dichotomous view of microbial status (sterile vs. infected), leading to "one-size-fits-all" treatments that primarily target pathogens but neglect the complex host-microbiome interaction. The RESTORE hypothesis is that re-establishing the healthy respiratory microbiome core using a probiotic composed of lung-specific commensal bacteria and/or their derived metabolites can mitigate pneumonia severity by modulating pathogens and mucosal immunity. My main objectives are: 1) define lung-specific bacterial consortium and their derived metabolites/peptides, whose elimination is associated with pneumonia severity; 2) test their effects in vitro on commensal bacteria and pathogens; and 3) evaluate their impact on pathogens multiplication, microbiome composition, and lung mucosal immunity. I will use data from existing cohorts to identify bacterial consortia with pneumonia severity and integrate multi-omics data to characterize these consortia and their metabolic products. Then, I will assess the interactions within the bacterial consortium and their effects on pathogens by analyzing the growth and transcriptional responses. Finally, I will investigate their therapeutic potential in pneumonia mice models, focusing on pathogen burden, microbiome composition, transcriptomic activity, and immune modulation using single-cell RNA sequencing and flow cytometry. RESTORE represents a pioneering approach by leveraging the lung microbiome to develop non-antibiotic, lung-specific strategies, addressing the complexity of pneumonia pathophysiology beyond pathogen eradication. By employing a multi-disciplinary integration of cutting-edge methodologies, this project could revolutionize pneumonia treatment and potentially extend to other infectious diseases.

Mots clés : microbiome, nosocomial pneumonia, bacterial pathogens, probiotics, metabolites peptides, mucosal immunity, mice pneumonia models, immune modulation, multi omics data, host microbiome interaction

Participants :
- Université du Michigan (Etats-Unis) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Nantes Université (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 242260.56 €
Projet UNIT-FIX (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : SIGNED

Marine microbes, while only representing 1% of the photosynthetic biomass on Earth, contribute nearly half of global net primary production. Nitrogen (N) is one of the most limiting nutrients in the ocean, controlling marine phytoplanktonic growth and carbon storage. The primary source of nitrogen in the ocean is nitrogen fixation, a process achieved by diazotrophs using the nitrogenase enzyme. Over the last 20 years, the biological knowledge on nitrogen fixation has significantly evolved with the advent of meta-omics data (i.e., high-throughput sequencing of full communities). It is now clear that diazotrophs are a diverse group with various lifestyles, growth strategies and metabolisms, allowing them to occupy a wide range of ecological niches. Yet, climate models models fail to capture diazotroph diversity, leading to uncertainty in predictions of future marine primary production. The advent of marine big data, including large scale environmental meta-omics datasets, offers a chance to bridge biological diversity observations with biogeochemical modelling to enhance marine ecosystem future predictions in a changing climate. In UNIT-FIX, I aim to take advantage of the wealth of public meta-omics data to achieve three overarching goals: (1) develop a holistic and data-driven description of diazotroph diversity, (2) implement diazotroph diversity into data-driven modelling frameworks, and (3) improve predictions of the future states of diazotrophs and associated impacts on marine productions in a changing climate. These goals will be reached by bridging genome-level omics data and state-of-the-art modelling methods, including niche modelling, metabolic modelling and biogeochemical modelling. Highlighting key actors from marine microbial ecosystems and paving the way for their integration in climate models, UNIT-FIX will contribute to Sustainable Development Goals 13 and 14 of the United Nations: Climate Action and Life Below Water.

Mots clés : biogeochemical modelling meta omics diazotrophy nitrogen

Participants :
- Université de Bristol (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 276187.92 €
- Nantes Université (France) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet EvoZyme (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The ongoing climate change requires immediate actions to reduce the CO2 concentration in the atmosphere. One such action is the transition from a fossil-based to a bio-based economy that builds on CO2-derived one-carbon (C1) feedstocks like formate. To this end, synthetic C1 assimilation routes are being engineered into biotechnological relevant microbes. Among them, the reductive glycine pathway (rGlyP) bears enormous potential for biotechnological applications as it is short, energy efficient, and easy to engineer. So far, optimization of growth on formate via the rGlyP was achieved by adaptive laboratory evolution, a time-consuming process that leads to incorporation of undesired mutations and does not allow targeted pathway optimization (debottlenecking). In EvoZyme, I aim to develop a Synthetic Biology platform for targeted evolution of pathway enzymes. This platform consists of specialized Escherichia coli strains that are equipped with state-of-the-art diversification machineries allowing tunable hyperdiversification/evolution of target enzymes. Furthermore, the platform is capable of transferring the diversified enzyme libraries to various bacterial hosts. To benchmark the platform, I aim to debottleneck the rGlyP by targeting its core enzyme, the glycine cleavage system (GCS) which catalyzes the rate-limiting step of glycine synthesis. Diversification and optimization of the GCS will be tested in dedicated selection strains from different bacterial hosts that can only grow if a functional GCS is expressed. Ultimately, optimized GCS variants will be expressed in a formatotrophic E. coli strain lacking a GCS. Improved formatotrophic growth will be analyzed in lab-scale bioreactors to determine techno-economic parameters required for the establishment of a formate bioeconomy. The platform developed in this project will enable debottlenecking of rate-limiting enzymes in virtually any pathway and presents a valuable tool for Synthetic Biology.

Mots clés : synthetic biology, directed evolution, metabolic engineering, c1 metabolism, biosensors, bioeconomy

Participants :
- Conseil supérieur de la recherche scientifique (Espagne) — Coordinator, beneficiary, Recherche, subvention : 165312.96 €
Projet SolProDet (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

Self-powered near-infrared (NIR: 0.7–2.5 μm) deteSelf-powered near-infrared (NIR: 0.7–2.5 μm) detection technologies attract immense interest both from scientists and industry experts due to their vital applications in environmental monitoring, night vision, and imaging in remote locations. However, available conventional NIR photodetectors (PDs) are based on costly fabricated inorganic semiconductor materials or toxic heavy metal-containing quantum dots (QDs), which restrict their use in electronics and biomedical applications. Silver chalcogenide-based (Ag2E, E= S, Se, Te) QDs have recently joined as new promising toxic heavy metal-free materials for NIR detection, making them appealing from health and environmental safety perspectives. Nevertheless, the development of Ag2E-based NIR PDs is in its initial stage and far behind the commercially available devices due to the lack of protocols for device-relevant thin film fabrication with favourable device architecture. In this project, we propose a novel approach to solve this issue, which consists of two strategies: (i) chemical synthesis of small Ag2E and MAgE alloyed QDs followed by thin film preparation with favourable legend and thickness, (ii) PD architecture with proper electrode and electrode distance. To achieve this, the first strategy will develop synthesis protocols to control the size of Ag2E QDs and optimize their absorption and electronic properties by ligand exchange for NIR PDs application with different metal electrodes and electrode distances. In the next stage, the potential metal alloy will be introduced into Ag2E QDs by cation exchange, followed by studying the optical and electrical properties to optimize the synthesis and thin film quality for self-powered NIR PDs. In the last stage, the work will concentrate on the optimization of photodiodes using the best-suited Ag2E and MAgE QDs and demonstrate the application potential and related extensive characterization of these devices for upscaling.

Mots clés : nir photodetector, qds metal alloy, metal exchange, self powered photodetectors, qds photodiode, 

Participants :
- Leibniz-Gemeinschaft (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 87993.86 €