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

Visualizing protein-ligand interactions at atomic details is key to understand how ligands regulate macromolecular function. This knowledge could be leveraged to develop pharmaceutics utilizing the structure-based drug discovery platform. However, determining experimental structures of such complexes is often difficult using theVisualizing protein-ligand interactions at atomic details is key to understand how ligands regulate macromolecular function. This knowledge could be leveraged to develop pharmaceutics utilizing the structure-based drug discovery (SBDD) platform. However, determining experimental structures of such complexes is often difficult using the traditional time-consuming approach of hunting for suitable crystals for X-ray analysis. Recent breakthroughs in single-particle cryo-EM have overcome this limitation and enabled us to obtain atomic resolution structures of complex biomolecular systems. Though cryo-EM can now provide very high-resolution data of the overall system (less than 2 angstroms in many cases), unfortunately, resolutions of ligands are often significantly low to be useful for SBDD. Parallel to developments in cryo-EM, computational methods for modeling and refining structures into EM maps have been developed, but their main focus has been to build accurate protein structures. Here, I propose to exploit the increased computing power of molecular dynamics simulations offered by high-performance computing and algorithm development to develop a cryo-EM data-driven computational modeling approach to fit ligands into low-resolution EM maps. After testing in a large data set, this approach will be applied to identify ligand binding sites in new EM maps of a membrane protein and investigate how binding regulates the functional landscape of proteins. The findings of this proposal could open new avenues in the drug design platform by leveraging the power of cryo-EM and computational chemistry to accurately model ligand-protein complex structures.

Mots clés : cryo em, ligand protein interactions, md simulations

Participants :
- KTH Institut royal de technologie (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 222727.68 €
Projet SCARAB (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

My goal as a MSCA fellow is to obtain a clear picture of the extent, distribution, and enrichment of the circumgalactic medium (CGM) gas around galaxies, refine our understanding of how gas flows through it, and establish observational connections to the galaxies that host it in order to shed light on long-standing questions about the CGM's integral role in galaxy evolution. This research, based on an unprecedented new dataset from the 4MOST/ByCycle survey that increases available halo absorber sightlines by three orders of magnitude, has the potential to change our view of how galaxies work and will generate a legacy data set that astronomers will use long into the future. Working with Celine Peroux at the European Southern Observatory (ESO) in Germany, I will contribute my expertise in quasar absorption-line spectroscopy and the Milky Way CGM, and benefit by extending my existing knowledge about the CGM to higher redshifts while developing data science skills through management and statistical analysis of large data sets.

Mots clés : circumgalactic medium, baryon cycle, galaxy halos, quasar absorption line spectroscopy

Participants :
- European Southern Observatory (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 202125.12 €
Projet ModEMUS (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

Cancer is the second most important cause of death in Europe, with an estimated 2.27 million new cases and 1.3 million deaths in 2020. The prerequisite for a successful medicinal therapy is that the drug reaches its target and that toxicity towards healthy tissue is limited, however the systemic injection of drugs leads to less than 1 % of the drugs accumulating in solid tumours. Relying on the permeability of the blood vessel in cancer tumours, the encapsulation of drugs in nanoparticles (NPs) constitutes a promising approach for cancer treatment. However, the homogeneous distribution of NPs in the tumour tissue remains a challenge. To reach all cells in the tumour the NPs must cross the extracellular matrix (ECM), a major component of solid tumours consisting mainly of a network of collagen fibres embedded in a hydrophilic gel of proteoglycans. Together, they limit the diffusion of drugs across the tumour. Focused UltraSound (FUS) exposure has been reported to improve the delivery of NPs to tumour cells. FUS induces acoustic radiation force and cavitation that can lead to microstreaming or shock waves but the underlying mechanism(s) for the improved transport are not well understood. Successful delivery depends on many factors including the pathology, structure and composition of the diseased tissue, the characteristics of the NPs, and the exposure parameters of the FUS, making it a complex problem difficult to solve using an experimental approach. In this project, we will use molecular modelling to identify correlations between the molecular details of NPs and ECM, and FUS exposure parameters with NP transport across the ECM, creating a predictive model for FUS delivery of NPs and drugs to diseased tissue. The model, validated by experimental data, will contribute to the design of personalized medicine for improved NP-based drug delivery.

Mots clés : molecular modelling nanoparticle transport drug delivery ultrasound irradiation langevin dynamics

Participants :
- Université de Stuttgart (Allemagne) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Université norvégienne de sciences et de technologie (Norvège) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 210911.04 €
Projet ImmunoMet (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Stroke is one of the leading causes of death and disability worldwide. Despite recent improvements in stroke prevention and acute treatment, there is still a very urgent need for promoting stroke recovery to improve patients’ quality of life. Microglia are the predominant brain resident immune cells, in charge of brain homeostasis through immune surveillance. Emerging evidences suggest that post-stroke microglial reactivity remains incompletely resolved and persists chronically. ImmunoMet aims to study the impact of persistent inflammatory and dysfunctional traits of microglia during stroke recovery through metabolic reprograming, a set of essential processes key to satisfy the high energetic requirements of immune activation. To fulfill this goal, ImmunoMet will use novel and cutting-edge methodologies, including sophisticated imaging techniques, multiparametric flow cytometry, metabolomics and single-cell RNA sequencing, to investigate the time course evolution of microglia immunophenotype and the potential shifts in microglial metabolic pathways over the course of stroke. ImmunoMet will also evaluate the effects of an acute manipulation of microglia cellular metabolism on the stroke recovery, as an approach to tackle chronic neuroinflammation and improve brain functional recovery after stroke. To this end, ImmunoMet aims to assess microglia immunophenotype in two scenarios: (1) a transgenic mouse line with altered microglia type I IFN signaling, which may regulate energy metabolism, and (2) after administering an itaconate derivate, a modulator of immune cell polarization. ImmunoMet is expected to contribute novel and valuable insights into the immunometabolic adaptations to stroke. This research will be a crucial for future development of therapies aimed at enhancing the long-term recovery of stroke survivors, addressing a significant socio-healthcare challenge. ImmunoMet will be a major step in my academic career as an international independent researcher.

Mots clés : neuroimmunology, stroke, recovery, microglia, metabolism

Participants :
- Conseil supérieur de la recherche scientifique (Espagne) — Coordinator, beneficiary, Recherche, subvention : 165312.96 €
Projet RHEA-Tolerant (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

The urgent need to combat pollution necessitates a focused reduction in CO2 emissions, positioning nuclear energy as a promising alternative to fossil fuels. The demand for advanced materials in nuclear fission and fusion power plants arises from their challenging operating conditions. While current materials are in use, there is a compelling case for exploring new alternatives that offer improved efficiency, enhanced safety, reduced waste, extended operational lifespans, high-temperature durability, and resistance to high-energy neutron irradiation. High-Entropy Alloys (HEAs) have emerged as a promising solution due to their exceptional properties and untapped compositional possibilities. Their key advantage is sluggish diffusion, which limits the movement of point defects, leading to increased recombination and mitigating hardening and swelling effects. To meet the stringent requirements of reactor environments, HEAs must also exhibit low activation properties. To tackle this challenge, our research focuses on understanding ion-irradiated single-phase HEAs under high-temperature and high-fluence conditions. We aim to uncover the underlying physics of hardening and swelling using a comprehensive suite of experimental and simulation techniques, including TEM, HR-TKD, Astar strain mapping, ACOM, nano-indentation, SIMS, XRD, AFM, micropillar tests, APT, DBS-PALS, DFT, MD, and KMC. The ultimate goal is to develop a robust screening tool with high-throughput capabilities, enabling the efficient evaluation of numerous HEA compositions. This tool will provide a foundation for tailoring HEAs to specific applications. The designed HEAs will not only withstand extreme conditions but also retain balanced mechanical properties, striking an optimal trade-off between hardness and toughness. This progress will pave the way for innovative applications in next-generation nuclear reactors.

Mots clés : rhea, nuclear power plant, irradiation hardening, swelling, radiation tolerance, he irradiation, bubbles, tem, ebsd tkd, dft

Participants :
- Université de Southampton (Royaume-Uni) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Université technique de Prague (Rép. Tchèque) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 207758.16 €
Projet KpIspE (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

Due to the current antimicrobial resistance crisis, addressing underexplored targets to afford anti-infective compounds with novel modes of action is urgently needed. Antimicrobial resistance not only poses a threat to public health, but is a substantial cost burden on the healthcare system. This proposal focuses on the design and synthesis of novel inhibitors of the target 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase (IspE). IspE catalyzes the fourth step in the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway which is essential for medically relevant pathogens (e.g., Enterobacter coli, Klebsiella pneumoniae, Mycobacterium tuberculosis and Pseudomonas aeruginosa) but entirely absent in humans, making this enzyme a promising drug target. We will initially explore drug fragments through the screening of carefully constructed fragment libraries, followed by hit-to-lead optimization for promising compounds. Target confirmation will be performed using a biologically active small-molecule photo-crosslinking probe and a crystal structure of IspE obtained in complex with a promising inhibitor. The investigation of potential for therapeutic intervention via inhibition of IspE will result in several potent inhibitors, enhancing the knowledge of this underexplored enzyme target and opening up access for further exploration of potent inhibitors. This research will greatly contribute to the discovery of novel anti-infective agents, leading to decreased morbidity and mortality in patients, economical benefits for the health care system in the European Union as well as globally.

Mots clés : anti infective, ispe, hit to lead optimization, fragment growing, methyl erythritol phosphate pathway

Participants :
- Helmholtz-Gemeinschaft (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 173847.36 €
Projet LuxSoM (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Microbes live as members of a microbial consortium where they interact with neighboring organisms (including their host) via the secretion of signaling molecules and through other types of cell-cell interactions. The root microbiome is comparable to the ’gut microbiome’ of the plant, important for optimal root growth, nutrition and providing resistance to abiotic and biotic stresses. The major mechanisms of microbial plant-recruitment from the soil and formation of microbial communities are unknown. The practical exploitation of these mechanisms will lead to innovative solutions for a sustainable agriculture, in order to mitigate the upcoming challenge associated with climate change. Main members of the root microbiome are Proteobacteria, as they account for 50% of the bacterial population, and LUXOM project aims to generate critical insights on their assembly and cell-cell communication mechanisms via a well-defined and targeted approach. LuxR solos, which evolved from cell-cell signaling quorum sensing systems (QS), are very widespread and exclusively found in proteobacteria. They are a family of transcriptional regulators that respond to endogenous or exogenous (also of plant origin) signals. The LuxR solos will be studied by genomics, genetics, molecular biology, analytical and molecular chemistry, biochemistry, microbiome analysis and state-of -the-art mass spectrometry based technologies. The importance of bacterial LuxR solos in the plant (root)-microbiome network will be explored to unravel their influence on plant host physiology and microbial community dynamics. Understanding cell-cell signaling in the root microbiome will be used to design bacterial communities of interacting plant-beneficial strains that will serve as a probiotic for plants to enhance plant health and sustainable agricultural productivity. Thus, LUXOM will unravel the first major cell-cell signal players for plant (root)microbiome establishment.

Mots clés : quorum sensing, microbiome, plant associated bacteria, luxr solo, contact independent signaling, regulation, syncom

Participants :
- University of California System (Etats-Unis) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- International Centre for Genetic Engineering and Biotechnology (Italie) — Coordinator, beneficiary, Recherche, subvention : 190895.12 €
- Conseil national de la recherche (Italie) — Partner, associated partner, Recherche, subvention : 0.0 €
Projet PaCeInDH (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : SIGNED

Rapid escalation of building energy use has raised concerns all over the world, and existing predictions express that this increasing trend will aggravate energy crisis and serious environmental problem. The district heating (DH) system that incorporates renewables and the thermal energy storage component shows favorable prospects as a supplier to serve residential and commercial consumers for space heating and domestic hot water. The operation temperature of the DH system is becoming lower to achieve a more energy efficient, sustainable, and eco-efficient system. This trend results in the performance degradation of the thermal storage when integrating the water tank to the DH system, resulting in potential economic losses. Meanwhile, a large heat storage and released rate cannot be achieved for the water tank with the limited size under the low temperature operation conditions. Compared with sensible heat thermal energy storage, the latent heat thermal energy storage (LHTES) is advantaged by its use of phase-change materials (PCMs) with high energy storage density at a near-constant phase-change temperature. To enable an energy efficient low temperature DH system, an appropriate storage medium with great thermophysical properties and low cost will be selected. The technical viability and practical applicability of the entire heating system will be experimentally and numerically investigated. A hybrid agent-based model predictive control (MPC) framework will be further built as a promising solution to achieve an effective energy management for the low temperature DH combined LHTES system. It is projected that the energy and economic performance of the DH combined LHTES system could be guided by the agent-based MPC. The capability of the agent-based MPC for performance enhancement will be finally calibrated and evaluated, and high-quality experimental research will be conducted for the validation of this hybrid control method outputs.

Mots clés : district heating system, latent heat thermal energy storage, phase change material, agent based model predictive control, energy and economic benefits, experimental and numerical

Participants :
- Université norvégienne de sciences et de technologie (Norvège) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 210911.04 €
Projet CASSIS (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Soft tissue sarcomas (STS) are rare, aggressive cancers. About 50% of patients with high-risk STS die within 5 years after diagnosis, highlighting the need for novel treatment approaches. A major obstacle for novel treatment design is our limited understanding of STS as ecosystems, shaped by diverse tumor cells and their interactions with cells of the microenvironment. Emerging strategies that target cellular relationships in STS are promising, such as immune checkpoint inhibition. First clinical trials assessing immune checkpoint inhibition were promising, but success varied greatly among different STS subtypes and a rational selection of patients was not available. A comprehensive description of the complex cellular diversity and interactions in STS tumor ecosystems and links to disease progression are currently missing. Here we will combine simultaneous detection of single-cell transcriptomes and cell surface proteins with 32-plex immunofluorescence imaging to characterize STS tumor and immune cell diversity with single-cell spatial resolution in seven STS subtypes. The STS subtypes include dedifferentiated liposarcoma, Ewing sarcoma, myxoid/round cell liposarcoma, clear cell sarcoma, desmoplastic small round cell tumor, fibromyxoid sarcoma, and solitary fibrous tumor, present with poor prognosis and are promising candidates for immunotherapies. Objectives are (1) to characterize the cellular diversity and tumor-immune interactions in STS ecosystems using simultaneous single-cell transcriptomics and cell surface proteomics, (2) to profile the STS immunoenvironment with single-cell spatial resolution in situ, and (3) to functionally assess candidate tumor-immune interactions in vitro. This project will provide the first single-cell atlas for seven STS subtypes and will enable a better understanding of STS tumor ecosystems, pave the way for novel precision oncology approaches, and facilitate the identification of candidates for immunotherapy clinical trials.

Mots clés : sarcoma cancer, tumor ecosystem, immune profiling, tumor immune interactions, single cell transcriptomics and cell surface proteins, multiplexed immunofluorescence imaging, rare cancer

Participants :
- Helmholtz-Gemeinschaft (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 189687.36 €
Projet MASS2 (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry imaging (MSI) is increasingly used for clinical application. Based on untargeted, spatial chemical information, tissue samples can be analysed with superior density of information compared to conventional histology techniques. However, MALDI suffers from several significant limitations like strong ion suppression effects, inherently low ion yields limited to a few classes of polar to mid-polar analytes, and impeded detection of low-weight compounds. This crucially hampers a comprehensive analysis of complex biological samples. Strategies for post ionisation (PI) – most prominently MALDI-2 – significantly increase the ion yields for numerous mid-polar and polar compounds. Surface-assisted LDI (SALDI) uses photoactive surfaces, which feature specific ablation and ionisation that can majorly extend the range of detectable compounds and can be prepared in a superiorly homogeneous manner for SALDI-MSI. The proposed study aims to develop a novel means for extensive metabolome and lipidome analysis by SALDI-PI-MSI to overcome limitations of MALDI. Therefore, a new PI strategy coined Single-Photon Induced Chemical Ionisation (SPICI) will be combined with functionalised Au layers for comprehensive tissue characterisation of an extended polarity range with high mass resolution. The versatile software package rMSI will provides the computational means for the analysis of the complex measured data sets. We will apply our approach to human samples of bladder cancer tumour and achieve detailed monitoring of physiological processes in the cancerous tissue in unpreceded analytical depth. Newly identified biomarkers will help the urgent need for prognostic and diagnostic means for cancer. This comprehensive approach can be a massive generator of hypotheses for disease characterisation and foster the implementation of MSI into further fields of medical research and help to mature MSI in a multidisciplinary fashion.

Mots clés : instrumentation

Participants :
- Université Rovira i Virgili (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 165312.96 €
- Aliri France (France) — Partner, associated partner, Organismes privés (hors enseignement), subvention : 0.0 €