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

Neurodevelopmental disorders (NDDs), including Fragile X Syndrome (FXS), are a heterogeneous group of conditions leading to difficulties with speech, learning and other neurological functions greatly affecting patients and healthcare, societal, and educational systems. The rising prevalence of NDDs highlights the urgent need to understand their origins, often rooted in early cortical development. In humans, the cerebral cortex, responsible for cognitive functions like language and learning, is susceptible to disruptions during early brain development, a process tightly regulated by neuronal growth and protein synthesis. The coordination of biochemical events in eukaryotic cells, including protein synthesis, is facilitated by compartmentalizing key molecules either into organelles or as membraneless condensates via liquid-liquid phase separation (LLPS). LLPS is crucial for neurotransmission, memory, and synaptic plasticity. The fragile X messenger ribonucleoprotein 1 (FMRP) has been shown to undergo LLPS with the translation factor 4E-BP2 (eukaryotic initiation factor 4E binding protein 2), a key regulator in the mechanistic target of rapamycin (mTOR) signaling pathway implicated in both autism and FXS and the development of cortical outer radial glia. The Neuro-Phase project will investigate the role of LLPS and the molecular and cellular mechanisms involved in NDDs and more specifically the role of 4E-BP2-FMRP LLPS interaction in translational control and early human brain development which has yet to be explored. To test this hypothesis, the Neuro-Phase project will use innovative biological models, including human induced pluripotent stem cell-derived brain organoids and organotypic cultures of post-mortem human embryonic cortical explants. This project will provide critical insights into the pathogenesis of NDDs by identifying potential therapeutic targets, that leverage cellular intrinsic mechanisms like LLPS, to mitigate or prevent these conditions.

Mots clés : neurodevelopmental disorders, neurobiology, early human brain development, translational control, corticogenesis, fragile x syndrome, asd, liquid liquid phase separation

Participants :
- Foundation for Research and Technology Hellas (Grèce) — Coordinator, beneficiary, Recherche, subvention : 181423.68 €
- Université de Liège (Belgique) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet DARETOTIP (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : SIGNED

Society is currently struggling to manage a complex set of socio-ecological challenges related to climate change. Solutions range from reducing our consumption to novel technology used to decouple the economy from its impacts. Regardless of the strategy, materialising the green transition into a low carbon society means crossing a social tipping point (STP).  An STP occurs when the collective action of a population reaches leads to wide-ranging systemic change. STPs can be triggered by bottom-up approaches like consumer boycotts, or top-down interventions like policies, tax disincentives, and trade agreements. The problem is that, so far, STP have only been described qualitatively and the mechanisms beyond their emergence remain poorly understood.  The overall project goal is to provide a deeper understanding of which types of change allow society to move towards a more sustainable status, specifically by unveiling the role of social tipping points in reaching sustainability.  I intend to use system dynamics (SD) to study social tipping points quantitatively. SD is a modelling approach to simulate feedback loops between variables in a system. SD is a perfect fit to the quantitative study of STPs for two reasons. First, it is a flexible tool to model coupled human and natural systems (CHANS), whereby ecological processes exhibit changes over time under the influence of human drivers. Second, it allows one to determine when changes in elements of the system lead to the crossing of a tipping point and to a different system configuration.  My combined expertise in CHANS and SD, supported by my supervisor’s background in sustainability assessment make us an ideal team to conduct this research. Not only that, this fellowship will improve my research profile providing a steppingstone towards my career goals.

Mots clés : system dynamics, sustainability, climate change, life cycle assessment

Participants :
- Université d'Aalborg (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 214934.4 €
- Leibniz-Gemeinschaft (Allemagne) — Partner, associated partner, Recherche, subvention : 0.0 €
Projet sleepyTau (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Dysfunction of protein Tau is the main cause of dementia. Dementia associates with synaptic failure and sleep disturbances, but their connection remains elusive. In dementia, Tau becomes hyperphosphorylated (p-Tau) causing synaptic loss. Temperature fluctuations also associate with Tau phosphorylation, for example in hibernating animals. Intriguingly, my work demonstrates that brain temperature decreases during sleep, and further evidence suggests there are Tau-sites phosphorylated during sleep. My hypothesis is that sleep (and temperature)-induced Tau phosphorylation drives synaptic plasticity changes during sleep. To investigate this, I will map the dynamic changes in p-Tau during sleep and then delve into the mechanisms by mimicking brain temperature changes that naturally occur during sleep in human-induced neurons and mouse primary neurons. Employing genome engineering, I will interfere with p-Tau during sleep in mice in vivo and evaluate its impact on sleep, sleep-dependent synaptic plasticity and hippocampal long-term potentiation. This research challenges the notion that p-Tau solely drives disease progression, exploring a physiological function for p-Tau in regulating synaptic plasticity during sleep. The result of this project can challenge our understanding of Tau's function and open a new therapeutic avenue: the development of sleep-wake mechanisms to reverse the pathological p-Tau state observed in dementia. With my host lab's prior track record of uncovering critical insights into Tau-induced synaptic dysfunction, it stands as the perfect platform to tackle these questions. Additionally, I find myself in an ideal position, armed with exciting preliminary data that bolsters the validity of this proposal, and a robust technical and scientific background that empowers me to embark on this ambitious research journey. The plan I propose brings us closer to breakthroughs in effective dementia treatments.

Mots clés : temperature, sleep, tau, phosphorylation

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 175920.0 €
Projet SemiLIOM (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

The detailed understanding of quantum many-body effects is a highly relevant task in modern condensed matter physics. It is assumed that quantum many-body systems generically exhibit a notion of ergodicity, captured by the eigenstate thermalization hypothesis. However, it is numerically observed that there exist various ergodicity-breaking effects, which violate this assumption of fundamental thermodynamics. The most prominent example of such ergodicity-breaking is many-body localization (MBL), which arises from an emergent integrability induced by local integrals of motion. Despite the conceptual analytic intuition, most investigations on many-body localization are confined to small-sized numerical studies, only. The project goes beyond this state in devising an analytical view on ergodicity-breaking by combining concepts from many-body physics with modern classical and semiclassical techniques. The aim of this project is to rigorously transfer the notion of classical integrability by means of the Kolmogorov-Arnold-Moser (KAM) theory towards the emergent integrability of MBL in the semiclassical regime. To this end, the study provides a detailed understanding of the transition from MBL to ergodicity, and thereby lays out the foundations for a many-body KAM theory in terms of symplectic geometry. Furthermore, as entanglement is the central observable of ergodicity-breaking, the project is complemented with an analytical investigation of entanglement in the semiclassical regime. The current advances in the experimental realization of quantum simulators and quantum computers render this project to be highly relevant and timely. The completion of the project will provide the missing link between classical KAM theory and quantum mechanics and establishes a firm foundation for future investigations of the quantum-classical correspondence in many-body systems.

Mots clés : semiclassical physics, many body localization, ergodicity breaking

Participants :
- Université de Liège (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 200400.0 €
Projet DETECTIVE (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Despite significant medical advancements, cancer remains a major cause of mortality worldwide, and several cancer types still lack efficient therapy, in part due to resistance to traditional immunotherapy (IT). Endothelial cells (ECs) present an important yet overlooked modulator of tumor immunity, possessing an immunosuppressive nature, and proposed to contribute to IT resistance. Studies of the host lab indeed identified immunomodulatory features in EC subsets (coined IMECs). My central hypothesis is that targeting immunosuppressive (IMMUSUP) genes in tumor ECs may promote anti-tumor immune reaction to overcome resistance and improve the efficacy of traditional IT. The aim of this work is to identify novel, IMMUSUP genes expressed by tumor ECs and assess the potential of targeting these genes in vivo to promote anti-tumor immune response. I will explore in particular “mystery genes” (with poor functional annotation, ca 1/3 of the mammalian coding genome and an unexplored resource of potential targets) to maximize the identification of novel IMMUSUP genes beyond the currently used targets in traditional IT. Thus, I will (i) identify and prioritize EC IMMUSUP genes using artificial intelligence/machine learning approaches and (ii) in silico bioinformatics coupled to a mystery-genome wide siRNA screen to reveal IMMUSUP activity; (iii) confirm IMMUSUP targets via lipid nanoparticle-based siRNA delivery to generate EC-specific knockdown mice in models of lung, esophageal, and liver cancer; and (iv) determine the Mode of Action of the most promising targets using multidisciplinary approaches. My work will yield insights about previously unknown drug targets in tumor ECs, potentially paving the way for development of alternative IT with enhanced efficacy. My prior experience in immunology and bioinformatics combined with the host lab's expertise in EC (dys)function and single cell -'omics' technologies will ensure high quality execution of this project.

Mots clés : alternative immunotherapy immunology tumor microenvironment immunomodulatory endothelial cells artificial intelligence machine learning single cell rna sequencing

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 191760.0 €
Projet GreenNP (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

A fundamental area of solid state physics is the study of electrons, nuclei vibrations (phonons), and their interactions in crystals, known as electron-phonon interactions (EPIs). EPIs determine the temperature dependence of the bandgap, and lead to conventional superconductivity, among many other important phenomena. EPIs are usually studied using lowest order perturbation theory, which is only valid when the coupling is weak. However, strong EPIs have been reported in many key materials. For example, there is a huge gap renormalization of about 3 eV in high-pressure hydrogen that makes it metallic, and understanding metallic hydrogen is considered a substantial step towards understanding high-temperature superconductivity in hydrides. Research on the gap renormalization and temperature dependence of the gap of diamond is also very active, with exciting possibilities in the development of LEDs for use in extreme environments like high temperatures. However, existing calculations are not well justified, or perturbative approaches do not match experimental data. In GreenNP, we will study these and other effects due to EPIs using a rigorous nonperturbative adiabatic Green's function approach that the experienced researcher (ER) Dr. Jean Paul Nery has recently developed. Strong assets of the project will be the use of first-principles as opposed to models, and the inclusion of anharmonicities. First-principle calculations will be implemented into one of the prime open-source packages of the community, in collaboration with its renowned leading group at a nearby university; and a secondment will be carried out with a specialist in anharmonicities. By the end of the project, through the study of elemental semiconductors and insulators, there will be a clear understanding of the effects of strong EPIs in electronic properties. The ER will be taken to a leadership position in the field of EPIs and higher-order effects, with excellent future career prospects.

Mots clés : electron phonon interaction, electronic spectral function, first principles, bandgap, temperature dependence, forbidden reflection, semiconductors, insulators, diamond, high pressure hydrogen

Participants :
- École polytechnique fédérale de Lausanne (Suisse) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Université de Liège (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 191760.0 €
Projet SLYDIV (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Many bacteria possess a paracrystaline protein coat named the S-layer. S-layers cover the entire cell surface and are involved in protection, virulence, cell-shape maintenance and communication. Lattice integrity is essential for S-layer function, meaning that its assembly must be intimately coordinated with cell growth and division. Some studies have reported that S-layer biogenesis co-localizes with peptidoglycan (PG) synthesis, however, the underlying molecular mechanisms remain unknown. Here, I will investigate the molecular regulatory network that orchestrates S-layer assembly, cell division and PG synthesis in the human pathogen Bacillus anthracis, where S-layer defects render the bacterium avirulent, making this ultrastructure an attractive therapeutic target.  In the SLYDIV project I will 1) structurally and functionally compare Sap and EA1, the exponential and stationary phase S-layer proteins of B. anthracis 2) follow their in vivo assembly using time-resolved labelling and fluorescent microscopy and 3) uncovering the molecular interactions that couple S-layer assembly with the PG and/or cell division machinery. I will make use of chemicals that selectively target the cell cycle or cell division and monitor localization of S-layer assembly, will use nanobodies that disturb S-layer integrity and monitor the localization of cell wall synthesis, and use my interactomics experience to discover contact partners of S-layer and PG synthesis. Thus, SLYDIV is a multidisciplinary and integrative project that combines structural biology, biophysics, cell imaging, and microbiology. In addition, SLYDIV meets my solid knowledge on bacterial cell division with the host labs’ expertise on S-layer structure and function. The SLYDIV project aims to lead to a major breakthrough in the basic understanding of the regulation of the bacterial cell envelope, while it will pave the way for specific novel molecular therapies against B. Anthracis, a Category A bioterrorist agent.

Mots clés : s layer cell division nanobodies cell envelope peptidoglycan

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 175920.0 €
Projet HEROCO2 (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

Carbon capture, utilization and storage (CCUS) technologies are considered crucial for reaching carbon neutrality. Biocatalysis could offer sustainable alternatives to utilize emitted CO2 as building block for green industrial processes. However, CO2 low solubility in aqueous media and high stability result in low substrate availability for the enzymes and in thermodynamic limitations. In this project we propose to address two challenging CO2 biotransformations: i) the reduction to methanol; ii) the carboxylation of methional to 4-methylthio-2-oxobutanoate (MOTB), that can be further aminated to give the L-methionine amino acid. However, only high CO2 concentration can lead to high product yield and overcoming thermodynamic limitations. The purpose of the HEROCO2 project is to overcome these limitations through the design of hierarchical porous heterogeneous biocatalysts. The final material will be obtained by the assembly of microporous nanostructured sorbents, deputed to generate reservoirs of CO2 surrounding a macroporous material acting as carrier for the enzyme cascades. CO2 controlled desorption from the micropores is expected to keep high local CO2 concentrations within the macropores where the enzymes are immobilised, allowing out-of-equilibrium reactions under atmospheric pressure conditions. The selected cascades will be immobilized together with the corresponding cofactors, resulting in self-sufficient biocatalysts. Deep eutectic solvents (DESs) will be selected as green solvents since they combine high CO2 solubility with the preservation of enzyme activity. The two biocatalytic pathways will be finally tested in continuous flow reactors. This project could inaugurate new sustainable technological routes for carbon capture and utilization, addressing significant environmental challenges and advancing the field of biocatalysis towards carbon-negative processes by introducing innovative approaches never explored before.

Mots clés : enzyme immobilization carbon capture and bio utilization hierarchical materials deep eutectic solvents continuous flow reactors self sufficient biocatalyst biocatalysis

Participants :
- Université d'Aveiro (Portugal) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Centre for Cooperative Research in Biomaterials (Espagne) — Coordinator, beneficiary, Recherche, subvention : 194074.56 €
Projet LAROSSE (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

To conquer land, vascular plants evolved a sophisticated root system, which consists of primary and lateral roots (LRs). The de novo LR organogenesis represents a major evolutionary innovation, which has provided sessile organisms like plants with the capacity to forage for water and nutrients. The host lab is a pioneer in demonstrating that LR formation requires de novo specification of stem cells inside the primary root. They also discovered that the early stages of LR initiation are regulated by an oscillatory mechanism where the phytohormone auxin plays a major role. Despite these advances, the exact molecular mechanisms underlying lateral root stem cell (LRSC) specification remain largely elusive and it is not known how these mechanisms emerged during plant evolution. To address these fundamental questions, I will use an emerging model system Ceratopteris richardii (C-fern), which is an evolutionary pivotal, yet underexplored model plant. Based on fossil records, ferns and seed plants diverged during the middle Devonian period from a common ancestor suggesting that several key regulators might be conserved among them, despite some differences in their root ontogeny. In C-fern, the formation of LRSCs is clearly visible at the anatomic level. C-fern has ancestral and possibly simpler mechanisms underlying LRSC specification. In this project, I aim to identify key transcription factors controlling LRSC specification in C-fern. To achieve this goal, I will combine my expertise in molecular and developmental biology with multidisciplinary approaches including single cell RNA sequencing, CRISPR/Cas9-based genome editing and top-notch confocal imaging. This project has a strong potential to introduce novel concepts in the field of plant stem cells and their evolution. It will also open new perspectives for me to become an independent researcher in the field of evo-devo of plant stem cells.

Mots clés : lateral root development stem cell specification root development plant organogenesis root evolution fern ceratopteris richardii evo devo

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 191760.0 €
Projet ReKUPFFERate (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Liver fibrosis is the build-up of scar tissue resulting in impaired liver function. It can have different causes including alcohol abuse, obesity and viral hepatitis. For reasons that we do not fully understand, patients with fibrosis (termed cirrhosis) are more susceptible to infections. In fact, 50% of hospitalized patients with liver cirrhosis and infection die, highlighting the scale of this problem. Macrophages (MFs) are immune cells present in every tissue of the body that function to eliminate pathogens. In the liver, one subset of MFs, the Kupffer cells (KCs) are perfectly equipped with scavenger and pathogen recognition receptors to do this. Moreover, they are positioned in the bloodstream meaning they are one of the first cells to sense and respond to circulating pathogens although their precise roles have not yet been elucidated. In cirrhosis, KCs are reduced in number, being replaced by distinct MF subtypes, including a population termed lipid-associated MFs (LAMs). Preliminary data from the host lab demonstrate that both KCs and LAMs from the cirrhotic liver respond less efficiently to infection when compared with their healthy counterparts. Thus, I hypothesize that the altered MF landscape in cirrhosis and fibrosis is one mechanism driving the increased susceptibility and exacerbated responses to infection in these patients. Here, I aim to test this hypothesis by examining how the different MFs respond to infection in the presence and absence of fibrosis. Using novel mouse models specifically targeting the distinct MF populations, coupled with ex vivo cultures of human hepatic MFs, I will tease apart the mechanisms through which MFs exert their effects and attempt to manipulate these to recuperate normal MF numbers and functions potentially uncovering novel therapeutic approaches to limit infection and improve cirrhotic patient health.

Mots clés : macrophages fibrosis cirrhosis infection macrophage niche liver kupffer cells lipid associated macrophages lps

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 175920.0 €