Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet CMEndoMod (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The integrity of the endothelial barrier is vital for maintaining healthy brain function and is especially compromised in pathological conditions such as cerebral malaria. Despite its significance, the current understanding of the mechano-chemical mechanisms operating at sub-cellular, inter-cellular, and tissue scales within endothelial barriers during cerebral malaria remains limited. This project aims to close this knowledge gap by integrating advanced in vitro experimental methods with multi-scale mathematical models. Through a multi-tiered methodology—including single-cell assays, 2D endothelial monolayer cultures, and 3D brain microfluidic devices—we plan to assemble a comprehensive dataset that captures the complex mechano-chemical processes underlying endothelial function and dysfunction. This rich dataset will facilitate the data-driven development, calibration, and validation of a new multi-scale mathematical model, along with a high-performance computational framework for its solution. The validated models will subsequently be used to design targeted experiments aimed at dissecting the molecular mechanisms regulating endothelial integrity. Our interdisciplinary approach is uniquely poised to cultivate a dynamic interplay between experimental data and mathematical modelling, leading to a more holistic understanding of the mechanisms responsible for endothelial integrity in healthy states and how they are compromised in the cerebral malaria condition. Ultimately, this strategy aims to provide an in-depth understanding of the endothelium, which could, in the long term, aid in the development of therapeutic interventions for cerebral malaria.

Mots clés : endothelial cell, parasite, cerebral malaria, microfluids, mathematical modelling, finite element

Participants :
- Laboratoire européen de biologie moléculaire (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 181152.96 €
Projet QDGPUS (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

Quantum Darwinism describes how quantum systems lose their quantum properties and become classical and objective due to interactions with the environment. The standard Copenhagen interpretation simplifies this process as an instant wave function collapse. Understanding the details of this quantum to classical transition is an essential scientific as well as a philosophical question. Practically, it could lead to better isolation of quantum systems, resulting in more efficient experiments, and reduced errors in quantum computers. This project will utilize Graphics-Processing-Unit(GPU)-accelerated numerical simulations to model the environment and its interaction with the system of interest in detail. The simulation software will be developed from pre-existing software created by the Researcher, resulting in a fast and efficient process. Recent advances in GPU technology will enable the study of around 30 qubits (or equivalent for other systems). These simulations will be used as a tool and a testbed to study the dynamics of the Quantum Darwinist quantum to classical transition process, and to explore the impact of the initial state and internal dynamics of the environment. Firstly, we will study different measures of nonclassicality, particularly one based on the Kirkwood-Dirac quasiprobability distribution, and compare and correlate them with quantum discord, usually used in the context of Quantum Darwinism. We will also model weak measurement and its impact. Secondly, we will find the mathematical conditions for the emergence of a Spectrum Broadcast Structure (a condition stronger than Quantum Darwinism), with respect to the environment's initial state and dynamics. Thirdly, we will study in detail the compatibility of objectivity and thermal states, and intermediate phases that might emerge during the transition. The software developed will be made open-source, and published with an instruction manual for the benefit of the scientific community.

Mots clés : quantum darwinism, quantum foundations, quantum information, numerical simulations, gpu accelerated simulations, 

Participants :
- Université de Gdańsk (Pologne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 163166.16 €
Projet NanoMag organoids (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

*Neuromuscular disorders, whose incidence and prevalence have increased over time have currently no cure, and understanding their pathological mechanisms remains challenging due to the lack of reliable human in vitro models. A groundbreaking approach involves human 3D trunk neuromuscular organoids (NMOs) that replicate the cellular diversity and the functional dynamics of the neuromuscular system. However, the absence of in vivo-like external stimulations leads to reduced contractions and prevent terminal maturation, restraining their applicability for studying long-term neuromuscular diseases. The primary goal of this project is to design innovative multi-disciplinary approaches to mimic in vivo mechanical and brain inputs and provide new paradigms for organoid generation. A new method will be developed to apply spatiotemporally controlled nano-forces within NMOs, with the aim of enhancing the maturation of both the neural and muscle tissue. Additionally, magnetically induced nano-forces will be exploited to guide the reconstruction of the corticospinal tract within newly generated cerebral-NMOs and integrate brain inputs. Cutting-edge imaging, optogenetics, and single-nucleus RNA sequencing will be used for in-depth characterization of the outcomes. The hypothesis is that these stimuli will significantly promote NMOs maturation, resulting in a more sophisticated model for neuromuscular disease research. As case-study, the enhanced NMOs will be applied to model and explore the complex pathological mechanisms of X-linked spinal and bulbar muscular atrophy (SBMA). Patient-derived nano-forced cerebral-NMOs will be generated to investigate the impact of SBMA on neuromuscular system and corticospinal tract. Supporting this project will enable the implementation of innovative methodologies for the optimization of a relevant human in vitro system, with the potential to revolutionize research and treatment approaches for neuromuscular diseases.

Mots clés : organoids, neuromuscular system, mechanical forces, magnetic nanoparticles, tissue maturation, disease modelling

Participants :
- Max Delbrück Center (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 202125.12 €
Projet HD-BRECA (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Precision Oncology has revolutionized cancer therapeutics, mostly by matching genomic alterations with molecularly targeted agents. Yet, current predictive capacity is imperfect even in best-case scenarios (tumors driven by oncogene addiction against which a targeted agent exists). To push the field forward, we propose to exploit recent technological advances to analyze longitudinal profiles of cancer patients that encompass dimensions beyond the genetic profile: physiological monitoring, e-health records, patient-reported outcomes, medical imaging, and multi-omics. The integration of this multi-dimensional data with personalized genomics will allow an unprecedented level of understanding of cancer processes, identifying the features that drive patient disease trajectories, eliciting truly precision interventions. The goal of this project is to use this approach to improve the current predictive ability and break current efficacy plateaus in advanced breast cancers. I will integrate longitudinal data of a cohort of 100 hormone receptor-positive metastatic breast cancer patients in first line of treatment with CDK4/6 inhibitors and hormone inhibitors, monitored until disease progression or treatment failure. This constitutes the largest high-definition medicine study in advanced breast cancer patients to date. I will use data across 10 different modalities to establish disease trajectories, relate molecular features to clinical outcomes and build predictive models for prognosis. This integrative project combines translational and clinical oncology, engineering, and data science, to transition from the current genomics-centered precision oncology approach to high-definition oncology, a model in which deep longitudinal patient monitoring achieves a comprehensive personalized oncology.

Mots clés : breast cancer, longitudinal multi omics

Participants :
- Centre National de Recherches Oncologiques (Espagne) — Coordinator, beneficiary, Recherche, subvention : 165312.96 €
Projet Filcellstress (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Antimicrobial resistance is on the rise and it is predicted to become the first cause of death by 2050. One of the characteristic bacteria phenotypes of antibiotic resistance (and more generally of a stress response) is filamentation, which has been linked to survival strategies and virulence and is present in the most common form of bacteria in nature: biofilms. Thus, characterizing the filamentation phenotype opens the door to understanding the physiology and adaptation of bacterial cells under stress and during colonization processes. Filamentation results from a coordination of growth and division which are driven by the assembly machinery of the Fts system, the Min oscillatory system, and the nuclear occlusion system. In particular, Fts participates in the septum assembly, a ring-forming cell wall that will separate the daughter cells, whereas the Min oscillatory system restricts the assembly of the division machinery at specific locations to avoid nucleoid cleavage. When bacteria grow regularly, a single septum forms by the middle (symmetric division) to separate the nucleoids of daughter cells. However, when bacteria grow anomalously longer (filamentation), multiple nucleoids continue to segregate along the cell at regular intervals and several putative septa are created. Yet, filamentous bacteria do not grow indefinitely, and division events occur “randomly” (in terms of their timing and the selected septum). This raises the unexplored question of how size is regulated during filamentation processes. In this context, we hypothesize that the interplay between mechanical cues (e.g., filament bending) and changes in the bacteria membrane potential play a key role to regulate bacterial filamentation. Thus, the main objective of this project is determining how mechanosensitive and electrical properties of the division/growth machinery in E. coli regulate its filamentation.

Mots clés : biological physics, mechanobiology, bioelectricity, filamentation, size regulation, bacteria fision

Participants :
- Conseil supérieur de la recherche scientifique (Espagne) — Coordinator, beneficiary, Recherche, subvention : 165312.96 €
Projet MI-CORE (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Notwithstanding the ongoing race to develop new efficient energy storage and conversion technologies and reduce greenhouse gases in the atmosphere, the global emission of carbon dioxide (CO2) due to anthropogenic activities is reaching critic levels, posing a serious threat to a sustainable development. The major objective of this project is to open new avenues toward the capture and conversion of CO2 through the development of novel transition metal-based intermetallic compounds as catalysts for the electrochemical CO2 reduction reaction (eCO2RR). Identifying the active sites of a catalyst and the species involved in the CO2RR electrochemical process is a precondition for the rational design of top-performing catalysts exhibiting both high activity and high selectivity toward valuable products. For this reason, this project aim to understand the dynamic evolution of the catalysts by detecting the intermediate states of the reaction process in real time using state-of-the-art synchrotron scattering techniques, such as operando X-ray powder diffraction and X-ray absorption spectroscopy, to ultimately disclose the mechanisms of reaction. Reaching this goal is the key toward the successful design of technologically relevant catalytic systems able to effectively subtract CO2 from the atmosphere and convert it to useful and economically relevant chemicals.

Mots clés : catalysis, electrochemistry, green energy conversion, synchrotron radiation, operando investigation

Participants :
- AREA Science Park (Italie) — Coordinator, beneficiary, Recherche, subvention : 172750.08 €
Projet CryoCLEMAV (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Adenoviruses (AdVs) are very contagious viruses widespread in vertebrated. Human AdVs infections mainly affect children and immune-supressed people. On the other hand, AdV-derived vectors, nanocarriers and vaccines have turn out to be efficient therapeutic tools. Understanding AdVs disassembly mechanisms is vital to advance research in antiviral drugs, gene therapies, nanocarriers and vaccines. AdV particles’ metastability is key for surviving environmental conditions and cell defences, but at the same time, these particles should disassemble at the appropriate time and place during virus entry. The particle size and the speed of the process challenges the visualization of these events inside the cell. CryoCLEMAV aims at providing unprecedented structural insight on the process of virus entry and disassembly by combining virology with the cutting-edge microscopy techniques: correlative light and electron microscopy (cryo-CLEM), cryo-electron tomography (cryo-ET), FIB-milling and subtomogram averaging. This approach will allow to recapitulate the process with a previously unreachable resolution and specificity in a near native context of the host cell. CryoCLEMAV is an ambitious project whose success will be firmly supported by merging my expertise in virology and super resolution microscopy with the host lab knowledge and resources in cryo-EM techniques and adenovirus biology. Outcomes of this project will contribute to the development of several cryo-electron microscopy techniques and to the field of adenovirus biology, also impacting in the expanding field of adenovirus-derived therapeutic tools. All together will advance the research work of my host group, benefit the host organization (CNB-CSIC), and boost my professional career.

Mots clés : cryo electron microscopy, adenovirus, disassembly, cryo clem, cryo et, tomogram, 3d reconstruction

Participants :
- Conseil supérieur de la recherche scientifique (Espagne) — Coordinator, beneficiary, Recherche, subvention : 165312.96 €
Projet MAMllingIR (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The high calory intake and the sedentary behaviours represent one of the most common stress to which humanity is subjected. This is leading to an increased incidence of obesity that can be aggravated by dysfunctional metabolism, among which insulin resistance (IR) is the most common scenario. Two crucial processes know to lead to IR are Endoplasmic Reticulum (ER) stress and mitochondrial dysfunction. Mitochondria and ER are in tight physical contact through the mitochondria-associated ER membranes (MAMs), which are emerging as an important hub for glucose homeostasis. MAMs are involved in a plethora of cell functions, such as lipid synthesis, ROS and Ca2+ signalling, autophagy and inflammation, all processes tightly linked with cellular insulin sensitivity. In support to this notion, MAMs miscommunication was shown to occur in the presence of IR. Nevertheless, no conclusive molecular mechanisms can explain MAMs adaptation during IR. Furthermore, how MAMs remodelling affects the signalling between ER and mitochondria (Ca2+, ROS, lipid exchange) during IR progression and how this affects ER and mitochondria functions are still open questions. The overarching aim of this proposal is to characterize the alterations of intracellular signalling in mouse models of hepatic IR at the level of MAMs and to develop a standardized methodological approach to assess inter-organelles signalling changes during pathophysiological cues. To this goal, I will implement innovative approaches in vivo to quantify these contacts and to identify the MAMs molecular composition during IR. Furthermore, I will characterize the consequence of IR on MAMs signalling pathways by combining ‘omics approaches and imaging technics, to identify the molecular and functional signature of the MAMs during the IR in vivo and characterize new molecular pathways involved in the onset of IR in the liver.

Mots clés : mitochondria, endoplasmic reticulum, inter organelles contacts, intracellular signalling

Participants :
- Helmholtz Zentrum München (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 173847.36 €
Projet inviXTus-BAM (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Border-associated macrophages (BAMs) are macrophages that reside in specific anatomical interfaces between the brain and the blood circulation. Due to limited access to fresh human tissues from those anatomical sites, our understanding of human BAM development and function remains poor. It was previously observed that human hematopoietic stem cells from umbilical cord blood take up residence and differentiate into BAM-like macrophages when injected into the brains of neonatal mice expressing human colony-stimulating factor 1 (hCSF1). Single-cell RNA-sequencing confirmed strikingly similar transcriptomic signatures of those human macrophages to BAMs. The resulting chimeric mouse model represents an innovative platform in which the development and function of human BAMs could be investigated. In the current study, brain-xenotransplanted human cord blood-derived macrophages will be further characterized to assess whether they show location-specific molecular signatures, as do human BAMs. Then, an in vivo CRISPR knockout screen will be performed on those cells in order to decipher the genetic regulators of human BAM identities. I, the applicant, have extensive experience in brain immunology and in working with macrophages. I will work on developing and applying an in vivo CRISPR screen workflow in the chimeric mouse model developed by the laboratory of Dr. Movahedi (VUB, Belgium) who has established himself as a leader in brain macrophage research. This project will offer me the invaluable opportunity to learn genome editing techniques, design and execution of mouse experiments, as well as single-cell -omic experiments using state-of-the-art instrument. By bridging my existing knowledge with the cutting-edge techniques offered at the host laboratory, I aim to lay the foundations for an innovative system to study human BAMs.

Mots clés : macrophage, brain, neuroimmunology, crispr, neuroscience, inflammation

Participants :
- Vrije Universiteit Brussel (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 200400.0 €
Projet EMC-FLU (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Influenza virus infects the airway epithelium. The connective tissue underneath the epithelium consists of extracellular matrix (ECM) produced mainly by fibroblasts. Small airway fibrosis, characterized by fibroblast activation and excessive deposition of ECM, is emerging as the key driver of the progression of chronic obstructive pulmonary disease (COPD), a very common and life-threatening lung disease for which no cure exists. Irreversible progression of COPD is often triggered by influenza virus infection. However, causative mechanisms between influenza virus infection and small airway fibrosis have not been explored. In this project, the fellow will infect an advanced co-culture model of patient-derived airway epithelial cells and fibroblasts from the human lung to mimic the microenvironment of the airway. Cellular and molecular profiling of the fibroblasts will be performed by an unbiased approach using integrated and interdisciplinary methods. Especially, a unique mass spectrometry and bioinformatics workflow for deep molecular profiling of the ECM will be combined with state-of-the art single cell RNA-sequence analysis to discover profibrotic readouts. Then, she will use cells from COPD patients to translate the findings to the clinic. Finally, she will establish a host-gene specific knockdown co-culture model to elucidate the role of a specific protein that interacts with the ECM and assess the druggability of this potential target. The fellow is a pathologist from Japan with extensive experience in infection with animal models. Her expertise and knowledge in disease pathology will be integrated with the host's prestigious scientific environment. Establishment of international connections will facilitate her to become an academic leader with a unique and multidisciplinary profile to combat infectious diseases of the lung.

Mots clés : epithelial mesenchymal crosstalk, influenza virus, extracellular matrix, fibrosis, fibroblast, chronic obstructive pulmonary disease, airway, co culture, organoid, systems biology

Participants :
- Helmholtz Zentrum München (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 189687.36 €