Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet IntegrAMR (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The IntegrAMR project aims at unravelling a widespread DNA integration process that plays a critical role in the propagation of antimicrobial resistance (AMR). In alignment with the societal needs, the project will focus on a pathogen ranked as a high priority by the CDC and WHO, Acinetobacter baumannii. This pathogen is capable of natural transformation, a process allowing bacteria to take up exogeneous DNA for incorporation in their own genome. By unravelling the molecular mechanisms of DNA integration during natural transformation, this study will address how this conserved recombination process can alternatively favor or counteract the spread of AMR islands. This knowledge is crucial to understand how bacterial populations evolve and adapt rapidly to clinical treatments. The research will use a multiscale approach, from structural molecular biology to single-cell and multicellular systems. It will use customized next-generation sequencing, genetics, microscopy and mathematical modeling. To complement the scientific work, the project includes training and communication activities. Open access practices implemented in the dissemination of the results will maximize impact. This work will contribute to the global fight against AMR, advancing molecular microbiology, and fostering responsible research practices. The outcomes will not only enhance scientific understanding but also support the development of new strategies for AMR surveillance, benefiting both the scientific community and public health. Overall, the project will allow the candidate to pursue their desired career perspectives and apply to teaching or R&D positions, where microbiology and genomics expertise are in demand.

Mots clés : homologous recombination, natural transformation, multidrug resistance, horizontal gene transfer, helicase nuclease systems

Participants :
- Lyon-I université (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 226420.56 €
Projet GRIPP (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Intercellular communication between epithelial intestinal stem cells (ISCs) and their niche Paneth cells is essential for intestinal homeostasis. It deteriorates with age promoting disease onset such as inflammation and cancer. Thus, understanding age-associated alterations in stem-niche cell communication is crucial for developing interventions to optimize tissue function in later years.  To communicate, Paneth cells secrete ligands instructing proliferation and differentiation of ISCs. ISCs receive these ligands via the respective receptors on their plasma membrane. While the signaling pathways of their communication are comprehensively described, the secretory membrane transport from the inside of the cell towards the cell surface of the ligands and receptors are only poorly understood. This project will identify how ISCs and their niche cells direct the secretory transport of receptor and ligand proteins for efficient intercellular communication at the cell surface and how directed secretion functions as an intestinal homeostasis regulator. First, I will establish a novel optogenetic tool in intestinal organoids enabling spatiotemporal resolved tracing of synchronized signal secretion in ISCs and niche Paneth cells using live imaging. Second, I will reroute directed secretory transport by addition of GPI-anchors, targeted signaling motif and gene removal. In combination with transcriptomics, I will study the effects of disturbed secretion on intestinal homeostasis. Third, I will unveil alterations in directed secretory transport with age and age-related dysfunctions.  The proposed project will elucidate how directed secretory transport between ISCs and their neighboring niche cells determines stem cell function for tissue homeostasis. Overall, it holds the potential to uncover age-related changes in directed signal secretion, opening new avenues for treatments improving age-associated intestinal dysfunction.

Mots clés : tissue homeostasis, ageing, stem cell niche, organoids, cell cell communication, secretory membrane transport, optogenetics

Participants :
- Société Max-Planck pour le développement des sciences (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 202125.12 €
Projet MetaMOF (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The risk of prenatal onset of metabolic disorders is influenced by the maternal environment, which is inherited by the offspring through epigenetic modifications. Epigenetic modifications utilize metabolic substrates, highlighting the connection between epigenetics and metabolism. In Drosophila, one key epigenetic modification is the MOF-mediated acetylation of histone H4 at lysine 16 (H4K16ac), which is known to be intergenerationally transmitted from mother to embryo. This makes Drosophila an ideal model to study how maternally contributed epigenetic modifications and metabolites shape embryonic development.  MOF operates in two modes: maternal pools establish chromatin accessibility, while zygotic pools facilitate future gene activation. Given that embryonic metabolism is temporally coordinated during development, the role of epigenetic regulation in embryonic metabolism remains unexplored. To address this, I plan to investigate the temporal contributions of MOF in metabolic regulation during Drosophila embryogenesis. Specifically, the following aims will be undertaken: Aim 1: Understand the maternal contributions of MOF-mediated metabolic regulation. Aim 2: Investigate the zygotic contributions of MOF in metabolic regulation. Aim 3: Uncover the association of MOF with the MSL or NSL complex to provide a mechanistic basis for metabolic regulation.  These aims will be achieved through a combination of cutting-edge techniques involving metabolomics, RNA-sequencing, and epigenomics. This research will provide insights into metabolic regulation during early development and its implications for maternal impacts on offspring metabolism. The findings will enhance our understanding of the fundamental mechanisms underlying the epigenetic basis of metabolic regulation, with broader implications for developmental biology and disease.

Mots clés : mof, h4k16ac, zygotic genome activation, embryogenesis, metabolism, transcription

Participants :
- Société Max-Planck pour le développement des sciences (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 217965.12 €
Projet Barley-SymBioNet (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The rapid population increase and high demand for food production raise immense concerns about an upcoming global food crisis. Low soil nutrient levels are a key factor limiting crop yields, and farmers currently rely on extensive application of chemical fertilisers, which have severe negative environmental effects. The implementation of beneficial soil microbes with nutrient-sequestering functions has therefore become a mainstream interest, aimed at increasing crop productivity while reducing the ecological footprint of current agricultural systems. The Common Symbiosis Signalling Pathway (CSSP) plays a pivotal role in orchestrating symbiotic relationships between plants and arbuscular mycorrhiza fungi, as well as leguminous plants and nitrogen-fixing bacteria. These symbioses are vital for optimal plant nutrient acquisition, particularly nitrogen and phosphorus. While the functions of CSSP genes in arbuscular mycorrhizal symbiosis in cereals are well-documented, their impact on other beneficial microbiota, such as nitrogen-fixing bacteria, remains unknown. Unraveling these interactions is crucial for addressing contemporary environmental challenges related to crop nutrient limitations and organic fertiliser development. In the proposed project, we employ barley CSSP mutants and perform microbiome profiling, transcriptomics, and metabolomics approaches to elucidate the influence of CSSP genes on bacterial assembly, uncover genes involved in the interaction with beneficial bacteria, and identify CSSP-dependent root metabolites that govern plant-microbe signalling. Preliminary data showed that barley CSSP mutations significantly alter bacterial assembly, particularly reducing the colonisation by bacterial orders known for hosting plant growth-promoting isolates. A comprehensive assessment of cereal interactions with beneficial soil bacteria will provide the groundwork for future engineering endeavours aimed at addressing current environmental challenges.

Mots clés : plant microbe interactions, microbe microbe interactions, symbiosis signalling, nitrogen fixation, arbuscular mycorrhizal symbiosis, root exudates, sustainable agriculture, organic fertilisers

Participants :
- Société Max-Planck pour le développement des sciences (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 202125.12 €
Projet ReTraCol (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

One of the sources of genome instability is the occurrence of transcription-replication collisions (TRCs). These collisions occur when the replication machinery collides with the transcription complex due to the presence of obstacles in the DNA template, such as DNA-bound proteins or structures known as R-loops, which are three-stranded nucleic acid structures that inhibit the normal progression of both systems. These R-loops are often formed during transcription, but their assembly is regulated by several cellular mechanisms that prevent the accumulation of TRCs. TRCs can potentially cause deletions, chromosomal rearrangements, and loss of genetic information due to DNA double-strand breaks generated by the collision. High levels of TRCs have been found in several types of cancer, which is a growing global health concern. Although many studies have investigated the role of TRCs in normal and cancer cells, the detailed molecular mechanism behind TRCs remains to be elucidated. The ReTraCol project aims to bring together the fields of transcription and replication to gain a deeper molecular and structural understanding of R-loop-dependent TRCs using biochemical and cryo-EM techniques. The expected results will reveal how the replication and transcription systems behave during a collision and describe the stepwise formation of TRCs. This project could lead to an understanding of the impact of TRCs in both normal and cancer cells, and potentially open new future investigations to use TRCs as a cancer target.

Mots clés : replication, transcription, rnapii, r loops, cryo em

Participants :
- Société Max-Planck pour le développement des sciences (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 202125.12 €
Projet FGNRs (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

Graphene nanoribbons (GNRs) are the class of next-generation carbon materials that have emerged as promising candidates in future nanoelectronic devices. Their unique electronic, thermal, and magnetic properties heavily depend on their widths and edge topologies. Thus, the precise design and synthesis of GNRs is highly desirable with control over the structural factors with atomic precision. In this regard, the bottom-up synthesis approach plays a significant effort in constructing a wide variety of well-defined widths and edge structures. Moreover, the planer GNRs (zigzag, armchair, and gulf edges) were extensively explored, whereas curved GNRs (cGNRs) (cove and fjord edges) were scarcely reported. Although cGNRs exhibit novel edge topologies, narrow band gap, and high carrier transport mobility provide further opportunities in nonlinear optics and asymmetric catalysis. Thus, efficient synthetic strategies and precise molecular designs are highly desirable for the synthesis of curved GNRs. To address this gap, we propose the Rh-catalyzed stitching polymerization strategy for the construction of fjord-edged graphene nanoribbons (FGNRs). The proposal will systematically investigate the stitching efficiency through NMR analysis and examine the influence of alkyl chains on the synthesis and solubility of cGNRs. Additionally, the methodology will be extended to the synthesis of heteroarenes containing cGNRs, with a focus on their solubility in organic solvents for further optical and electronic property studies. Furthermore, a comparison will be made with the living chain growth polymerization strategy applied to the same substrate. Overall, this proposal will systematically address the challenges associated with the synthesis, characterization, and structure-property relationship of fjord-edged graphene nanoribbons to pave the way for advancements in the field of nanoelectronics.

Mots clés : fjord curved graphene nanoribbons cgnrs , rh catalyzed stitching polymerization, living chain growth polymerization, charge carrier dynamic, and thz spectroscopy

Participants :
- Société Max-Planck pour le développement des sciences (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 217965.12 €
Projet PorMatDesign (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : SIGNED

Through continuous interaction between computational fluid dynamics, mechanics of solids, material engineering, and machine learning, with my host, I will develop a novel and computationally efficient method, implemented in open-source software, for the multi-scale design of engineered porous materials (EPMs) that meet user-specified hydro-mechanical functional requirements. This computer-aided approach will accelerate the discovery of EPMs and shorten the time for technology development, and is aimed at EPM design for additive Manufacturing (i.e. 3D-printing). The basic notion of the proposed approach is: (1) to employ a dimensionality reduction techniques to obtain a low-dimensional proxy for the high-dimensional problem of characterizing a porous micro-structure, (2) to develop physics-informed neural networks (PINNs) for scale-specific hydro-mechanical simulation of porous media at the micro (pore) scale, the meso (pore-network) scale, and the macro (Darcy) scale, (3) to employ a physics-based coupling mechanism for scale-specific PINNs, allowing them to form a chain of neural networks for hydro-mechanical structure-property-performance (S-P-P) linkage, and (4) to incorporate a topology optimization algorithm for the multi-scale design of porous media. The focus is on fluid-saturated, poroelastic materials, with special emphasis on biomedical applications that require a defined porous structure, such as meniscus implants and bone scaffolds. I will work on the project at the University of Luxembourg (host institute), in collaboration with the University of Strasbourg (secondment institute).

Mots clés : porous materials additive manufacturing hydromechanical simulation multi scale physics informed neural networks optimization

Participants :
- Université du Luxembourg (Luxembourg) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 191760.0 €
- Université de Strasbourg (France) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet TRIFLUORO-BUNDLE (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

Organofluorine compounds are scarce in natural products, but they are central to therapeutic science, agrochemical development and materials research. Incorporation of fluorine atoms within an organic molecule can have profound effects on pharmacokinetic and pharmacodynamic properties. Enantiomerically enriched fluoro amino acids possess physiochemical and biological properties that distinguish them from canonical amino acids and are key to advances in biological sciences, including peptide and protein engineering. On another front, many azasugars that have high pharmacological potential suffer from weak binding affinities and inferior pharmacokinetic properties; this problem may be addressed through glycomimetics. A promising strategy in glycomimetics entails H-to-F and OH-to-CF2H exchange. A compelling objective in modern chemistry, therefore, is the development of efficient, and practical strategies for diastereo- and enantioselective synthesis of readily modifiable organofluorine fragments that have a CF2H moiety. However, while enantioselective methods that can be used to form a C(sp3)–CF2H stereocenter are available, none apply to the formation of products bearing a fully substituted carbon stereogenic center that has a CF2H and a F substituent. To address this problem, we will develop a robust, practical, and scalable catalytic strategy for practical, efficient, diastereo- and enantioselective conversion of nitriles to homoallylic amines with a CF2H- and F-substituted allylic carbon. Our investigations will focus on an important but severely underdeveloped class of transformations, namely, catalytic diastereo- and enanantioselective addition of a carbon-based nucleophile to nitriles. We plan to utilize the new catalytic approach as the key design element in highly efficient diastereo- and enantioselective syntheses of polyfluoro α-amino acids, and aza-sugars, bearing a fully substituted carbon stereogenic center that has a CF2H and a F substituent.

Mots clés : organofluorine compounds, homoallylic amines, diastereo and enantioselective synthesis, difluoromethyl and fluoro substituted stereogenic carbon, polyfluoro amino acids, polyfluoro aza sugars

Participants :
- Université de Strasbourg (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 211754.88 €
Projet FLUORMET (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

Practical strategies that provide facile access to tetrasubstituted olefins bearing a fluorine atom and/or a polyfluoroalkyl moiety are crucial to drug discovery and development and are therefore in high demand. Equally important and sought-after are reliable and stereocontrolled methods for modifying such alkenes. Nonetheless, such methods are scarce, and those available are severely limited in scope. In this context, catalytic olefin metathesis offers a unique disconnection to access modifiable tetrasubstituted alkenes in either stereoisomeric form. Still, there are no more than a handful of such reactions, with all ring-closing metathesis (RCM) processes affording a cyclic alkene bearing two methyl groups. There is only a single reported example of a cross-metathesis (CM) reaction that affords a tetrasubstituted olefin as a stereoisomeric mixture. Inspired by recent progress by the host group, we will develop new cyclic alkylidene catalysts that are designed to promote formation of stereodefined tetrasubstituted fluoro-alkenes by stereoretentive CM. The substrates will be readily available trisubstituted olefins and commercially available F/F3C-substituted alkenes. The products will be value-added tetrasubstituted olefins bearing a F/F3C moiety as well as a modifiable C–Cl or C–Br bond. The method will be applied to the synthesis of fluorinated analogues of natural products such as fluoro-pateamine A. Another key aspect will be application to the modification of important drugs. Our goal will be to utilize the new catalytic chemistry to generate analogues that might exhibit superior bioactivity, or be active in a different disease area. We will transform entecavir or barmumycin to their polyhalogenated analogues, which will be tested for in vitro bioactivity through collaboration with experts. The conversion of readily accessible olefins into their polyfluorinated, tetrasubstituted analogs holds considerable and as-of-yet untapped promise for drug discovery.

Mots clés : stereodefined tetrasubstituted olefins, organofluorine chemistry, olefin metathesis, cyclic alkylidene, late stage modification

Participants :
- Université de Strasbourg (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195914.88 €
Projet EduMoney (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Social Sciences and Humanities
Statut du projet : SIGNED

Financial literacy is necessary to spend our money wisely and understand how financial instruments work. In an increasingly complex financial landscape, today only half of the EU adult population has an adequate understanding of basic financial concepts. EduMoney tackles this issue from a historical perspective to offer the first systematic, comprehensive, and digital analysis of the skills and knowledge underpinning financial literacy during another period of increasing financial complexity: the medieval ‘Commercial Revolution’. The focus is on money ‘itself’, and how this was deployed and represented in Tuscan abacus manuals and merchants’ notebooks, the pedagogical tools of the time. The project analyses the period between 1202, when Fibonacci completed his Liber Abaci, and 1478, when the first printed abacus manual known as Aritmetica di Treviso was published. By adopting an interdisciplinary approach that combines methods from economic history, medieval literature, and the history of economic thought, with the support of the latest digital platforms for text analysis, I will digitise, transcribe, and translate a selected corpus of abacus manuals and merchants’ notebooks. This will allow a comparative and digital study of these sources to identify (cross-)references to money that will be grouped into ‘typological families’. The resulting categorisation will form the basis for an in-depth analysis leading to an innovative treatment of money as a heuristic and pedagogical instrument, and to a more holistic understanding of how people lived, learnt, and conceptualised their lives as economic actors. The enhancement of financial literacy among different age groups through a series of didactic and outreach activities will empower people by endowing them with the right tools to make informed decisions to improve their economic wellbeing, thus tackling social and gender inequalities for the development of a more inclusive Europe.

Mots clés : money, financial literacy, abacus manuals, merchants notebooks, tuscany, digital humanities, monetary history, financial history, history of the economic thought, history of education

Participants :
- Université de Fordham (Etats-Unis) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Université de Milan (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 265099.2 €