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

Chemotherapy resistance remains a major challenge in cancer treatment, often leading to poor patient outcomes. NatK aims to (1) identify predictive signature of chemoresistance and (2) develop innovative therapeutic strategies to overcome it, using triple negative breast cancer (TNBC) as a model. The focus is on natural killer (NK) cells, hypothesising that reactivating these cells could enhance their cytotoxicity against chemoresistant tumours. State-of-the-art 10X Visium spatial transcriptomics will be employed to analyse primary TNBC samples from chemotherapy responders and non-responders, mapping NK cell infiltration and activity within the tumour microenvironment (TME). Advanced bioinformatics will identify immune-related signatures of chemoresistance, validated in independent patient cohorts to develop a robust NK cell-related biomarker for patient stratification. To translate these findings into therapeutic strategies, specific genes upregulated in chemoresistant tumours will be targeted to enhance NK cell-mediated cytotoxicity. Co-culture systems with NK cells and patient-derived organoids will be used to evaluate the impact of gene modulation, followed by the development of small molecule inhibitors targeting promising candidates. The efficacy of combining NK cell activation with chemotherapy will then be assessed both in vitro and in vivo, aiming to establish a novel combination therapy to combat chemoresistance. NatK integrates state-of-the-art spatial transcriptomics, functional immune profiling and patient-derived organoid models to elucidate chemoresistance mechanisms. The insights gained may have broader implications, potentially extending to other cancer types and guiding targeted immunotherapy development. In line with the MSCA Postdoctoral Fellowship objectives, this interdisciplinary research will advance expertise in cutting-edge biomedical technologies, foster international collaboration, and contribute to advancing oncology in Europe.

Mots clés : nk cells, tumour immunology, chemoresistance, dna damaging agents, cancer treatment, preclinical models, patient derived organoids, co culture systems

Participants :
- Université de Bristol (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 276187.92 €
Projet AROMASWITCH (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

Aromaticity, a fundamental concept in the field of chemistry, is conventionally associated with planar, conjugated two-dimensional (2D) systems. Despite its theoretical description and potential application in optoelectronic materials, 3D aromaticity induced by strong through space frontier orbital interactions remains so far little explored. AROMASWITCH aims to exploit the complementary expertise and know-how of the host institute and the fellow to delineate the concept of Controlling Spatial Conjugation by the mechanical motion of switchable molecular tweezers. Our hypothesis is that using Ni(II)-porphyrin and/or norcorrole to place persistent, enriched π-electron at both ends of a tweezer will (a) generate three-dimensional through space conjugation in an optimized distance between two “face-to-face” oriented macrocycles and (b) influence the resultant (anti)aromatic character of the whole system. This approach is innovative as such through space π conjugation has not yet been explored in the molecular tweezer. We will develop macrocycles-terminated switchable molecular tweezers (i) to tweak the through space electronic conjugation in an “on” and “off” mode and (ii) to investigate the impact of 3D conjugation on aromatic property-driven photophysical and electrochemical properties. In addition, we will (iii) inspect the three-component tweezer systems in the context of the guest binding study, intercalation of aromatic or antiaromatic motifs and optoelectronics applications. The project will thus enhance our understanding of stimuli-responsive and conformation-dependent 3D communication between (anti)aromatic rings and holds great potential for the development of smart materials with an optoelectronic response.

Mots clés : aromaticity, molecular switches, molecular machines

Participants :
- Sorbonne Université (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 211754.88 €
Projet SIMPLIFLY (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

We are constantly learning new motor skills throughout our life. Whether riding a bicycle or playing an instrument, motor learning relies on a calibration between sensory signals and internal motor information. Saccadic adaptation, the recalibration of fast eye rotations induced by visual error signals, has helped develop key insights into the identity of circuits, and the theoretical models underlying motor learning. However, how visual signals interact with internal movement representations during motor learning remains at present underdetermined. Taking advantage of the compact brain of the fly with well characterized visual pathways, and a plethora of anatomical, physiological, and genetic tools, here we propose to study motor learning in the context of goal-directed body saccades in D. melanogaster. We will monitor changes in body saccades consistent with repetitive visual perturbations by quantitative analysis of head-fixed flight behavior in an adapted version of the classical eye saccadic adaptation paradigm. In simultaneous, we will first record and then manipulate the activity of population of neurons known to contribute to body saccades, including visual descending neurons (VDNs) and their upstream synaptic partners, which as a network integrate visual signals and self-motion information with motor commands. Together, these experiments will establish unprecedented causal relationships among neural activity, learning, and the formation of a flexible internal representation for locomotor control. The functional principles identified in this project will establish a framework that can be tested in other species and behavioral contexts, and ultimately improve our understanding of motor learning with important implications both in health and disease.

Mots clés : sensorimotor integration vision motor learning drosophila calcium imaging virtual reality

Participants :
- Champalimaud Foundation (Portugal) — Coordinator, beneficiary, Recherche, subvention : 172618.56 €
Projet CryoFusion (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

With progress and development of society, the necessity of a more affordable, reliable and sustainable energy is crucial to stability and prosperity of ever-growing population. For this reason, fusion power is being researched and developed to obtain high amounts of stable and greener energy compared to conventionally fossil fuel-based and fission processes. Materials, which are being tested as possible candidates for fusion reactor components, are mainly based on the previous selections designated for fission nuclear power. However, their implementation is not easily transmittable and has been proven to be considerably challenging. Consequently, there is a high interest towards research of new development and processing (such as heat treatment) of selected materials applicable for fusion as well as materials that were not previously considered. The proposal suggests to conduct fundamental research on selected material (proposed alternative AISI 431) and its treatment, which has the potential to be used as material for fusion reactor components. The project tends to provide base understanding on how deep cryogenic treatment (DCT) improves materials’ properties for fusion applications through their microstructural tailoring. Focus is placed on the role of modified microstructure as well as nano-chemistry on the corrosion resistance, which is up to now only superficially explored. Due to the unique influence of DCT on microstructure, the process can provide a novel greener way of material treatment that is both highly effective as well as economically feasible. The proposal challenges promising alternative material for fusion and aims to show how DCT can effectively improve microstructure, corrosion and surface resistance of selected material. Furthermore, the project will also develop new fundamental knowledge of DCT effect on metallic materials in order to provide future possibilities and treatment combinations for materials used in fusion.

Mots clés : fusion, corrosion, surface engineering, magnetism, advanced synhotron and neutron measurments, material engineering, cryogenic treatment

Participants :
- Société Max-Planck pour le développement des sciences (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 189687.36 €
Projet QECANM (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

In recent years, the idea of building quantum technologies has quickly moved from being an intellectual curiosity to a practical reality and quantum metrology and quantum sensors are prominent ones, already in use in scientific and commercial applications. The underlying idea is to exploit genuinely quantum effects to perform extremely accurate measurements, with a precision not achievable by classical means. While many important theoretical and experimental milestones have already been reached, there are still many open theoretical questions left on the path to understanding the ultimate capabilities of quantum metrology, especially in realistic operating conditions. We have identified three main pillars that are currently subject to very active research: i) understanding the ultimate limits of the quantum estimation of multiple parameters simultaneously, either because all of them are of practical interest, or because a full prior characterization of additional system's parameters is not possible; ii) assessing the impact of environmental noise on the quantum probe, in particular beyond the standard assumption of uncorrelated noise; iii) understanding the limits of metrological schemes based on time-continuous measurements, nowadays feasible in many physical systems (e.g. superconducting qubits, optomechanics), which open the possibility to perform measurement-based feedback control on the system. The overarching goal of this action is to advance the state of the art in these three areas and to connect these three pillars, by devising new theoretical tools to assess the ultimate precision limits in novel and physically relevant scenarios. These tools will be rooted in quantum estimation theory and quantum control theory and they will provide fundamental benchmarks for the next generation of quantum sensors.

Mots clés : quantum metrology, quantum sensing, multiparameter quantum estimation, time continuous measurements, quantum trajectories

Participants :
- École normale supérieure de Pise (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 172750.08 €
Projet NOROXYSYN (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

Opiates, derived from the poppy plant and exemplified by morphine, are important medicines for pain and other disorders because of their agonistic action on the opioid receptors. However, many opiates have bad side effects such as respiratory depression, sedation, and constipation. They can be highly addictive, which leads to abuse and overdose deaths. To address these issues, “nal-compounds” have been developed, which attenuate the effects of opioid receptor agonists, making them useful for treating opioid overdose and abuse; examples include the World Health Organization essential medicines naloxone and naltrexone, which are µ-opioid receptor antagonists. Other nal-compounds include nalbuphine, nalmefene, and nalfurafine, which have a range of clinical uses. Noroxymorphone is a common late-stage intermediate in the synthesis of nal-compounds, which makes its synthesis a critical task. Noroxymorphone is manufactured semisynthetically from the poppy-derived compounds oripavine and thebaine. However, the quantity of oripavine and thebaine in poppies is low compared to the most abundant compound morphine. In addition, poppy cultivation is problematic; it is highly space- and resource-intensive, and could be affected by floods, droughts, disease, and geopolitics. Illegal poppy diversion also fuels the illicit narcotic trade (e.g., heroin), resulting in huge societal problems. Therefore, breaking human reliance on the poppy by developing an industrially viable total synthesis of noroxymorphone from inexpensive feedstocks would be game-changing.  Dozens of total syntheses of morphine and related compounds are already known, including one synthesis of noroxymorphone. However, none are remotely competitive with semisynthesis from poppy raw materials because of their step-count. In this MSCA Fellowship, we will use modern synthetic methods to develop a short (7/8 steps) lab-scale synthesis of noroxymorphone that is suitable for optimization for industrial manufacture.

Mots clés : target compound synthesis, natural product like synthesis, morphinan opioids

Participants :
- Université de Nottingham (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 276187.92 €
Projet PFDT-CSSE (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : SIGNED

This project is devoted to developing a rapid adaptive Digital Twin-based phase field fracture modelling technique, which will provide accurate prediction of damage initiation and propagation for advanced composite materials and structures servicing in extreme, multi-physics environments. This proposed rapid adaptive digital twin-based fracture computational framework will establish a direct connection and mapping between virtual simulations and real-world composite structural behaviours under multiphysics environments. A virtual modelling aided stochastic interval method will be applied for the quantification of system and multiphysical uncertainties. A computationally efficient fracture simulation technique, based on the Phase Field Cohesive Zone Model (PFCZM) and Broyden–Fletcher–Goldfarb–Shanno (BFGS) monolithic algorithm, will be developed to accurately predict the complex crack behaviours (nucleation, propagation, merging and branching, etc.) for advanced composite materials and structures (3D printed, lattice, FGM, FRP etc.). This action will, for the first time, overcome a series of technique challenges in the modelling and analysis of non-deterministic multi-physics fracture problems encountered in composite structures include: the damage diagnosis by fussing multi-physical sources of data; the high-fidelity computational complexity of composite crack simulation methods; identification, quantification and validation of uncertainty factors in damaged system under thermo-mechanical, chemo-mechanical, and electromechanical coupling conditions. Finally, the accurate fracture prediction methods developed in this project will enable rapid safety and reliability evaluation for advanced composite structures. Through this fellowship, the applicant, in conjunction with the team at Cardiff University (CU) will deliver internationally recognized research outcomes and techniques for advanced composite structures safety analysis and evaluation.

Mots clés : digital twin, phase field, composite material, non deterministic fracture, reliability assessment, safety evaluation

Participants :
- Université de Cardiff (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 276187.92 €
Projet DrugMOF (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : SIGNED

Drug delivery systems are often needed for delivering drugs in a targeted organ or tissue at a desired concentration range and without toxic side effects. Metal-organic frameworks (MOFs) have emerged as promising drug delivery systems due to their high loading capacity, but currently this is also their main limitation as it results in too rapid drug release in the human body, causing an excessive response and potentially toxic side effects. Slowing down the drug release rate, while maintaining high loading capacity and biocompatibility, would enable applications within especially cancer therapy.  Disordered MOFs (i.e., MOFs without an ordered crystalline structure) have smaller pores and more torturous pathways for drug release. The project’s proposed strategy is to load anti-cancer drugs in the crystalline MOF with high surface area and thus high loading capacity and then subsequently subject this material to an order-to-disorder transition, giving rise to slower drug release. This transition can be induced by either mechanical ball milling or thermal melt-quenching. Molecular dynamics and classification-based machine learning will be used to identify which local atomic structures are best correlated with drug release rate in disordered MOFs. Experimental validation will be performed to establish design principles for MOF structures with a tailored drug release profile.  The project builds on complementary expertise of the fellow applicant (disordered biomaterials, in vitro studies) and supervisor (MOFs, simulations, machine learning). Combined with the research and training environment offered by the host organization (Aalborg University, Denmark), this will ensure the achievement of this novel project as well as the dissemination and exploitation of the results. The goal is to develop principles for designing disordered MOFs for drug delivery. The fellow applicant will emerge from the project with new skills, and the capability to launch his own research group.

Mots clés : drug delivery, metal organic frameworks, glasses, molecular dynamics, machine learning, structure property relations

Participants :
- Université d'Aalborg (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 230774.4 €
Projet SHIMAERA (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

Precision spectroscopy is a rapidly advancing field, where advanced experimental and theoretical methods converge to measure fundamental constants and test the laws of nature with remarkable accuracy. In this MSCA project, I propose innovative laser spectroscopy experiments in molecular hydrogen ions (MHI) to improve the determination of the proton-to-electron mass ratio, a very important fundamental constant of nature. My current group at LaserLaB Amsterdam and the host research group at the Kastler Brossel Laboratory (LKB) in Paris are both key players in the field. The MHI spectroscopy experiments performed in Amsterdam, combined with the quantum electrodynamics (QED) calculation methods developed at LKB, have enabled an improved determination of the proton-to-electron mass ratio and the electron relative atomic mass. Thanks to these exceptional results, as of 2022 MHI spectroscopy contributes to the definition of the CODATA internationally recommended values of the fundamental physics constants. To improve this further, I will implement Doppler-free laser excitation of an MHI quadrupole and/or two-photon vibrational transition, perform precision laser spectroscopy of the excited transition, and extract an even improved determination of the proton-to-electron mass ratio by comparing the measured transition frequency to the theoretically predicted value. This MSCA fellowship will give me the opportunity to do outstanding research by combining my hands-on expertise in precision spectroscopy with the expertise of the host research group in frequency metrology and QED calculations. It will also give me the perfect platform to foster international collaborations within my personal scientific network and to lay out my longer-term research plans, including developing the first MHI-based optical molecular clock to advance novel applications across science and industry.

Mots clés : fundamental constants

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

RNA metabolism is regulated by multiple post-transcriptional layers, primarily orchestrated by RNA-binding proteins (RBPs). When disrupted these processes can lead to diseases like myotonic dystrophy type 1 (DM1), a rare inherited disorder affecting skeletal muscle. DM1 is caused by an expansion of trinucleotides in the DMPK gene, leading to accumulation of RNA foci and deregulation of RNA metabolism. The mutation was identified in 1992 but aspects of its pathophysiology are not understood and there is no cure.  A promising area of research is the potential alteration of the m6A epitranscriptome in DM1. A major discovery in gene regulation is the presence of modified nucleotides like N6-methyladenosine (m6A), which affect RNA fate. Defects in m6A have been linked to various diseases but its role in muscular dystrophies including DM1 remains unexplored. m6A is regulated by writers that add and erasers that remove the modification. In DM1, the erasers FTO and ALKBH5 are deregulated. Once added m6A marks are recognised by readers which mediate their cellular effects. m6A readers are crucial to skeletal muscle physiology but their involvement in DM1 is unknown.  EpiDM project hypothesises that altered m6A demethylases activity leads to hypermethylation, impacting RNA function and muscle physiology. Its objectives are to 1) map and characterize m6a’s role in DM1, 2) identify m6A readers involved in the disease and 3) explore the therapeutic potential of targeting m6A methylation to restore muscle function.  My expertise will be combined with the host lab’s by leveraging DM1 models and next-generation sequencing techniques to study m6A and RBPs, and developing innovative therapies. By pioneering this research EpiDM will uncover the regulation of novel RNA pathways in skeletal muscle, advancing understanding of DM1 and identifying new therapeutic targets for muscular dystrophies. Finally it aligns with European initiatives focused on rare diseases and epitranscriptomics.

Mots clés : myotonic dystrophy, epitranscriptomics, m6a methylation, rna, rna binding proteins, omics, trinucleotide repeat expansions, toxic rna, skeletal muscle, innovative therapies

Participants :
- Institut national de la santé et de la recherche médicale (France) — Coordinator, beneficiary, Recherche, subvention : 242260.56 €
- Sorbonne Université (France) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €