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

Recent breakthroughs in the field of quantum technologies combining academic and R&D efforts have demonstrated the potential of quantum networks for major applications such as long-distance secure communication or quantum cloud computing. One current challenge is to deploy quantum networks out of the lab for realizing their expected far-reaching societal and economic impact. A crucial requirement for reaching this goal is the realization of a quantum repeater that will be able to extend quantum links to continental distances. In this context, the use of integrated photonic platforms, allowing for low-footprint, alignment-free and mass-manufacturable quantum nodes, represents a significant resource for real-life applications of quantum networks. In this proposal, we provide a route for achieving this goal through the integration of rare-earth quantum memories on fiber-pigtailed glass photonic chips. This technology enables the storage of single photons in a platform that is compatible with integrated photonic circuits used to perform quantum gates and computations. We will demonstrate for the first time on-demand retrieval of photons in an all-fiber quantum memory then build the first elementary integrated quantum memory node with a multi-memory photonic chip that could readily be embedded in a DLCZ-like quantum repeater architecture. The goals set in this proposal are important milestones towards the achievement of robust application-ready quantum networks and the establishment of a European quantum internet.

Mots clés : quantum memories, quantum repeaters, quantum communications, entanglement

Participants :
- Conseil national de la recherche (Italie) — Partner, associated partner, Recherche, subvention : 0.0 €
- Institute of Photonic Sciences (Espagne) — Coordinator, beneficiary, Recherche, subvention : 181152.96 €
Projet CryoLipNano (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

RNA therapeutics are revolutionizing medicine, offering new treatment possibilities for diseases once considered undruggable. Central to the delivery of nucleic acids, especially mRNA, is the use of Lipid Nanoparticles (LNPs) – the most advanced and the only clinically approved gene delivery platform. LNPs protect mRNA from degradation, facilitate its transfer, and ensure delivery into the cell. Despite their potential, the therapeutic potency of RNA-LNPs remains limited due to suboptimal RNA delivery, with <10% of the administered RNA-LNP system reaching the cytoplasm. To this end, crucial gaps persist in our understanding of LNP structure, integrity and their impact on trafficking and RNA delivery. CryoLipNano aims to advance our knowledge on LNP ultrastructure and intracellular dynamics, by linking – for the first time – lipid composition, morphology, LNP integrity, mRNA localization and trafficking after endocytosis. By integrating physical chemistry with cutting-edge cryo-electron microscopy (cryoEM), advanced imaging techniques, and proteomic analysis, this study will address critical knowledge gaps, ultimately leading to the rational design of second-generation LNP platforms with enhanced efficiency and potency. Moreover, CryoLipNano will establish the first RNA-LNP research hub at the host institute and, alongside with the ERA Chair's launch of the country's first cryoEM facility, will create a new line of expertise in RNA-LNP characterization by cryoEM. This expertise will be valuable not only in Greece, but also for entities across Europe and globally. CryoLipNano will also focus on disseminating the lab’s presence, educating the scientific community and the public about RNA therapeutics and their structural analysis, and inspiring young scientists. Finally, the high-level science and training the fellow will receive, will significantly advance her expertise and enhance her future employability in the field of nanomedicine and RNA therapeutics.

Mots clés : lipid nanoparticles, mrna lnps, rna therapeutics, cryo electron microscopy, lnp morphology, lnp trafficking, nanostructure analysis, gene delivery

Participants :
- Fondation nationale de la recherche scientifique (Grèce) — Coordinator, beneficiary, Recherche, subvention : 197263.68 €
Projet WETNEURONS (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Perception depends on the representation of external information in the cortex. This information enters the nervous system thanks to receptor proteins in your sensory neurons. These receptors transform external energy into neural activity. It follows that, if you do not have receptors sensitive to an environmental property, you cannot perceive such property. For example, humans are not able to sense electric fields, whereas some fish can because they have electroreceptors.  A sense required for survival is wetness due to its role in thermoregulatory responses. Unlike insects, humans lack hygroreceptors sensitive to the level of moisture of the skin, yet we have clear sensations of wetness. So, how do we feel wetness? Researchers think that these sensations emerge from the integration of thermotactile signals in the cortex, but the location or cellular encoding of wetness in the cortex is unknown. Therefore, I propose to study the neural basis of wetness sensations in mice. The mouse is an ideal mammalian model for this because their thermotactile system is similar to ours and tools to measure neuronal activity can be combined with behaviour. Crucially, researchers have recently found a co-localised representation of thermotactile stimuli in the mouse cortex.  First, I will develop wet stimulators for use in mice based on designs from human studies. Second, I will measure wetness sensations in mice by developing a novel perceptual task. Third, I will use calcium imaging techniques to identify and study cortical neurons activated during wetness sensations. Finally, I will use optogenetics to provide a causal relationship between neural activity and wetness sensations. This project will advance our understanding of how wetness sensations emerge through cortical activity, even in the absence of a wetness receptor. The research output will advance our understanding of brain function, but also will be of interest to the clothing, cosmetic and virtual reality industries.

Mots clés : wetness perception thermotactile system somatosensation multisensory integration imaging cortical activity

Participants :
- Max Delbrück Center (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 173847.36 €
Projet sc-LAB2FATE (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Every time an egg is fertilised, the cellular diversity of an animal must be rebuilt from scratch. Therefore, a central question in developmental biology is how cells differentiate to acquire distinct fates. A combination of genetics, molecular biology, and microscopy approaches has led to fundamental discoveries. Recently, single-cell genomics has enabled the analysis of transcriptional differentiation trajectories at unprecedented scale and resolution. However, ordering single cells by transcriptome similarity only gives ensemble averages of differentiation trajectories and not the full spectrum of cell state transitions. It then remains unclear whether cells can commit to their fate at different stages of development or change differentiation trajectories. The sc-LAB2FATE project proposes to measure how single-cell transcriptomes change over time in living zebrafish embryos using a new RNA labelling methodology. This will reveal the full spectrum of differentiation trajectories during gastrulation, allowing to see not only the major routes of differentiation, but also rare alternative trajectories. Single-cell RNA labelling, biochemical nucleoside conversion and sequencing will be used to measure mRNA kinetics and transcriptome dynamics of zebrafish embryos at single-cell resolution. Spontaneous cell fate changes during normal development will be contrasted with induced cell fate changes upon cell transplantation from different cell types to decipher signalling interactions. This project will leverage single-cell genomics and traditional approaches in developmental biology to build a conceptual framework for analysing embryonic development as both a genetically programmed and a self-organised phenomenon, and to provide a general blueprint of how one can study perturbation response using metabolic labelling in living systems.

Mots clés : zebrafish development, cell fate decisions, single cell rna seq, rna labeling, cell cell interactions

Participants :
- Max Delbrück Center (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 189687.36 €
Projet MapGen (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Schizophrenia (SCZ) affects 20 million people worldwide and antipsychotics remain the only effective pharmacological intervention. However, one-third of people with SCZ do not respond to first-line antipsychotic drugs. In the absence of clinical biomarkers to stratify SCZ subtypes, all individuals receive the same initial intervention, and it takes >4 years on average before people with resistant forms of the condition receive suitable treatment.  My overall aim is to unravel the pre-symptomatic cell-type-specific genetic circuits contributing to differential treatment response in SCZ. To achieve my aim I will use an interdisciplinary approach that improves my technical and soft skills and further extends my international network through a two-year stay at Yale University, and three months secondment at Harvard Medical School. During the return phase, I will establish myself as an independent researcher and a suitable candidate for leadership of a to-be-established stem cell lab at the host institute.  Objectives are (O1) to identify cell-type-specific neuronal pathways associated with distinct neurotransmission imbalances in each SCZ subgroup using a human-based neurodevelopmental model. (O2) To determine the functional link between SCZ-associated risk variants and response to antipsychotics.  Method: I will couple advanced stem cell models (region-specific brain organoids) with single-cell RNA sequencing to generate cell-type-specific transcriptomic profiles of patient-derived brain organoids from treatment-responsive and treatment-resistant forms of SCZ. I will integrate the potential risk variants from SCZ-GWAS and use published functional genomics data to determine the genetic pathways and associated regulators implicated in the etiopathophysiology of differential response to antipsychotics.  Impact: identify distinct genetic makeup for each SCZ subgroup to serve as potential predictive biomarkers and points of therapeutic intervention.

Mots clés : schizophrenia, treatment resistance, organoids, hipsc, single cell rnaseq

Participants :
- Université Yale (Etats-Unis) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Hôpital universitaire Haukeland (Norvège) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 307939.68 €
Projet SUPPED (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Economic Sciences
Statut du projet : CLOSED

This project aims to develop tools and solutions that turn value-added tax (VAT) records into an information system that can support evidence-based policy making and the development of regions, industries and firms in general.

Mots clés : business transaction networks, networks, value added tax, geography, agglomeration

Participants :
- Institute of economics centre for economic and regional studies (Hongrie) — Partner, associated partner, Organismes privés (hors enseignement), subvention : 0.0 €
- Complexity Science Hub Vienna (Autriche) — Coordinator, beneficiary, Recherche, subvention : 199440.96 €
Projet SOCIALPLAST (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The ability to learn and adapt in response to diverse social experiences is fundamental for animal survival. While key defensive actions against social threats such as flight or fight are innate, previous social experience can guide the selection of the appropriate response to minimize future harm, such as the development of social avoidance following social defeat. The ventromedial hypothalamus is a key brain structure in the innate defensive system, and activity in its ventrolateral part (VMHvl) can mediate both social aggression and escape, yet how previous experience influences hypothalamic social threat processing is not understood. Recent evidence has shown that social defeat can promote functional reorganization of neural activity in this structure, but the mechanisms of such plasticity have not been studied. In this project proposal, I plan to systematically investigate experience-dependent synaptic and neuronal plasticity in the VMHvl. First, I will use state-of-the-art in vitro electrophysiological techniques in mice to comprehensively explore changes in synaptic transmission in this region following social defeat. Second, I will leverage a recently developed calcium imaging method combined with optogenetics to follow and manipulate synaptic plasticity in the freely behaving mouse. Together with ethological behavior quantification techniques, this approach will allow me to identify and causally test the in vivo functional consequences of defeat-induced plasticity in the VMHvl. If successful, this project will provide novel insights into the synaptic and circuit basis of hypothalamic adaptations to social defeat. Gaining a mechanistic and physiological understanding of neuroadaptations following social experiences will offer new targets for therapeutic manipulation of maladaptive responses to social adversity that underlie many psychiatric disorders and pose a significant public health challenge.

Mots clés : social behavior, synaptic plasticity, hypothalamus, electrophysiology, calcium imaging

Participants :
- Laboratoire européen de biologie moléculaire (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 188590.08 €
Projet Minor tri-snRNP (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Minor spliceosome is responsible for the removal of a rare class of introns that are present in many essential genes. Despite its fundamental importance, much information remains elusive for a comprehensive understanding of minor spliceosome assembly and the molecular basis of the diseases associated with its malfunctions in human. In this proposal, I will investigate the assembly process of U4atac/U6atac•U5 tri-snRNP (minor tri-snRNP) by isolating relevant complexes from human cells and determining their structures using cryo-electron microscopy (cryo-EM). The U4atac/U6atac•U5 tri-snRNP is the largest pre-assembled building block of the minor spliceosome. By applying cryo-EM and proteomics, we will reveal the spatial organization and composition of the minor tri-snRNP, while the structures of its assembly intermediates will shed light on the role of assembly chaperones in the tri-snRNP maturation. Consequently, these findings will provide clues as to how minor spliceosome assembles to achieve its complex function.  Recent advances in the field of cryo-EM have opened up the possibility to study large and dynamic spliceosomal complexes at a molecular level. With our lab’s expertise in pre-mRNA splicing, cryo-EM and mammalian cell culture, we are perfectly positioned to exploit these new technologies to gain mechanistic insights into the assembly of the minor spliceosome.

Mots clés : minor spliceosome u4atac u6atac u5 tri snrnp cryo electron microscopy assembly

Participants :
- Laboratoire européen de biologie moléculaire (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 195914.88 €
Projet BIFCOLC-QS (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Colorectal cancer (CRC) development and progression have been linked to the presence of pro-oncogenic bacterial strains in the intestine, such as Fusobacterium nucleatum, pks+ Escherichia coli and enterotoxigenic Bacteroides fragilis. These pathogenic bacteria produce toxins that can disrupt gut epithelial integrity resulting in heightened pro-inflammatory response, enhanced DNA mutations, and increased cell proliferation, which can eventually lead to adenoma formation. In addition, these bacterial pathogens show increased genotoxicity by forming invasive polymicrobial biofilms, thereby resulting in CRC development. Recently it has been reported that anatomical location plays a crucial role in CRC development, progression, microbial colonization, response to therapies and disease outcome. Indeed, right-sided CRC is generally associated with pro-oncogenic bacterial biofilms and is known to have an overall worse prognosis compared to left-sided CRC. Pathogenic bacteria use quorum sensing (QS) machinery in the gut for their communication, which is essential for biofilm formation. We aim to develop an intervention strategy employing QS machinery to engineer a probiotic bacterial strain with sensing and killing properties to detect and target these pro-oncogenic polymicrobial biofilms. The sensor device will detect autoinducers produced by pathogenic bacteria on encountering their biofilms, activating the killing device. The killing device expresses a biofilm degrading enzyme, Dispersin B, which will disrupt these biofilms and eventually kill the pathogenic bacteria residing in these biofilms by the type VI secretion system. These polymicrobial biofilms can act as a marker of CRC and help to understand the role of CRC-associated pathogenic bacteria in CRC development, which can eventually serve as a basis for developing future strategies for the diagnosis and treatment of CRC and other intestinal disorders associated with biofilms formed by pathogenic bacteria.

Mots clés : colorectal cancer, gut microbiome, synthetic biology, quorum sensing and biofilms

Participants :
- Laboratoire européen de biologie moléculaire (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 173847.36 €
Projet MAChro (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Chromatin modifications are essential for the transcriptional programmes underpinning development and cellular identity. However, an understanding of the causal function(s) of chromatin marks in gene regulation has lagged behind. Particularly, whether chromatin modifications linked with active transcription (active marks) have a causal function remains intensely debated, while the underlying mechanisms are poorly understood. This is due to technical limitations in the ability to precisely perturb chromatin marks in a locus-targeted manner. In this project, I will leverage cutting-edge (epi)genomic tools to systematically dissect the causal roles of key active chromatin marks—H3K4me3, H3/H4ac, and H3K79me2—, at a mechanistic and quantitative level. To directly link locus-specific active mark deposition to transcriptional responses, I will employ a novel epigenome editing technology that allows precise and targeted deposition of chromatin marks. By combining this advanced tool with unbiased genome-wide CRISPR screens using the orthogonal enCas12a system, I will systematically uncover the molecular mechanisms that decode the function of active marks. Additionally, I will dissect the quantitative effects of these marks on transcription at the single-cell level using a tunable epigenetic editing platform. If successful, this proposal will provide unprecedented mechanistic insights into the role of active chromatin marks, paving the way to new therapeutic strategies that harness precise epigenetic control of gene expression.

Mots clés : epigenetic editing, crispr, orthogonal crispr screens, chromatin marks, active marks, epigenetic mechanisms of gene activation, degrons, conditional destabilization domains, tunable epigenetic editing

Participants :
- Laboratoire européen de biologie moléculaire (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 209483.28 €
Projet MebaGINO (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Recent breakthroughs found that mechanical features of gene promoters influence nucleosome positioning through ATP-dependent chromatin remodeling enzymes. This finding challenges classical models of DNA-sequence-dependent histone recruitment. While mechanisms for the translation of DNA’s physical parameters to nucleosome positions are debated, their experimental validation is still pending. MebaGINO aims to address this fundamental gap in knowledge. Taking advantage of recent advances in time-resolved CryoEM, I will answer the following research question:  What is the biophysical mechanism underlying the influence of DNA mechanics on nucleosome positioning by INO80?  I will use the INO80 chromatin remodeler as a model system to understand how nucleosomes are positioned adjacent to gene promoters featuring specific mechanical patterns. Firstly, I will interrogate how the nucleosome translocation process will be stalled through substitution of ATP with ATP-analogues on DNA with varying stiffness. From these experiments, I will obtain molecular structures via single-particle CryoEM. Next, I will obtain molecular structures from short-lived states using time-resolved CryoEM. For this, I will contribute to the development of an automated platform for CryoEM sample freezing which will be made available to the scientific community via EMBL's Electron Microscopy facility. Finally, I will build a biophysical model explaining the influence of DNA mechanics on INO80’s translocation process. Thus, I will provide novel views onto the mechanical basis of gene regulation which are relevant beyond fundamental research as for example during cancer development.  During this project, I will receive extensive training on cutting-edge structural biology instrumentation while contributing with my nanotechnology skills. Combined with my biophysics background, this fellowship will enable me to establish an interdisciplinary research group focused on structural biophysics.

Mots clés : method development

Participants :
- Laboratoire européen de biologie moléculaire (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 217965.12 €