Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet G4-KuRE (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a widespread oncogenic virus, whose infection can cause Kaposi’s sarcoma, an incurable cancer frequent in immunocompromised individuals. Similar to other herpesviruses, KSHV establishes a latent infection in the host, characterized by lifelong persistence of the viral genome. Necessary and sufficient for latent infection are the virally expressed latency-associated nuclear antigen (LANA) and highly repetitive GC-rich sequences on the viral genome, named terminal repeats (TRs). While several studies have uncovered the importance of LANA in promoting KSHV DNA replication and segregation during latency, the essential role of the TRs remains poorly understood. In particular, the GC-rich regions contained in the TRs have been speculated to fold into G-quadruplexes (G4), secondary DNA structures that can function as replication barriers, but their roles remain elusive. A deep mechanistic understanding of the ways KSHV maintains itself in latency would be crucial to uncover a way to eradicate the virus from the infected cells, before the onset of Kaposi’s sarcoma, but this knowledge is missing, mainly due to the methodological limitations of investigating KSHV latent replication solely in cells. With this proposal, in aim to take advantage of the Xenopus laevis egg extract in vitro system to go beyond such limitations and to gain mechanistic insight in the role of G4s in the latency of KSHV. By combining my extensive expertise in the field of DNA replication with the deep knowledge of Prof. Sara Richter at the University of Padua in secondary DNA structures in viral genomes, I aim at mechanistically defining the strategies adopted by KSHV to maintain itself in latency and at identifying approaches to prevent viral maintenance in KSHV infected cells. The proposed project will have great societal impact on cancer prevention, and it will be pivotal for my scientific and personal growth into an independent junior group leader.

Mots clés : g quadruplexes, xenopus egg extracts, oncogenic herpesviruses, mass spectrometry

Participants :
- Université de Padoue (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 188590.08 €
Projet CRISIS (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : SIGNED

This project aims to expand understanding of workable governance models in times of crisis through an ethnographic study of the role of Bhutan’s Central Monk Body (CMB) in ongoing management of the impacts of the COVID-19 pandemic. The pandemic markedly increased global inequalities, and its socio-economic effects are still being felt in Bhutan. Within this crisis situation, structures of state power are being renegotiated. Bhutan’s historical Buddhist governance model was based on a seamless union between religion and state. The 2008 constitution created a separation between the two, removing the monk body from government. Yet monks seem to be playing a prominent, but little understood, role in Bhutan’s ongoing ‘whole-of-society’ crisis response. This project explores the questions this raises about the workability of Bhutan’s secularist governance model, derived primarily from the Christian West. It also brings this case into dialogue with decolonial research in religious studies, anthropology and governance studies to address the broader question of how governance can be (re)imagined to mitigate crises in resource-poor nations. Bhutan’s acclaimed success in pandemic management and its status as the only sovereign state in the Tibetan and Himalayan region makes it an important case. Yet it is one of the world’s least ethnographically studied places. Drawing on my experience, knowledge and networks as a former government researcher in Bhutan and native anthropologist trained in the West, I will: a) conduct fieldwork to document the CMB’s role in crisis management; b) analyse what this reveals about governance in practice through the lens of Bhutan’s historical Buddhist governance model; c) assess the broader implications for workable governance in times of crisis; and d) apply the findings in policy recommendations. Skills and experience gained through this timely project will facilitate my transition into practice-oriented research as the next stage in my career.

Mots clés : ethnography, himalaya and south asia, religion and politics, crisis management, governance

Participants :
- Université de Copenhague (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 263393.28 €
Projet HETLEWY (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Parkinson’s Disease (PD) is the second most common neurodegenerative disease affecting millions world-wide. PD pathophysiology is associated with protein aggregates called Lewy Bodies (LBs), and aggregation is impacted by cellular environment, post-translational modifications and genetic predispositions. Heterogeneity in the composition of LBs across the brain has consequences for neuronal cytotoxicity and although LBs are a main focus in PD research, only a limited number of projects have explored their heterogeneity. I will investigate LB heterogeneity at the single cell level for the first time -- enabled by technological developments of my host lab, the Mann group, namely Deep Visual Proteomics (DVP). DVP combines high-resolution microscopy, AI-aided image analysis and ultra-sensitive MS-based proteomics to analyse the proteome in a spatially-resolved manner. I aim to identify proteins whose levels correlate with LB heterogeneity, thereby classifying different LB phenotypes and finding ‘tipping points’ in LB maturation that drive cell death. I will first apply DVP to cell culture models overexpressing alpha-synuclein, a main component of LBs, to investigate the composition of LBs and determine candidates promoting various types of LB phenotypes. Such candidates, e.g., the already known tubulin polymerisation promoting protein (TPPP/p25), will be expressed in cells to confirm effects on the LB phenotype. In parallel, I will apply DVP to human brain tissue to identify differences in aggregates across stages of the disease and to distinguish between healthy and sick cells within the same tissue. This analysis will provide unique insights into the progression of the disease and may yield new therapeutic candidates.

Mots clés : lewy body protein aggregation alpha synuclein parkinson s disease single cell proteomics

Participants :
- Société Max-Planck pour le développement des sciences (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 173847.36 €
Projet LF13CMRI (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

Magnetic resonance imaging (MRI) is an excellent technique for medical diagnosis. Nonetheless, people from rural areas and low-income countries cannot access MRI due to its high associated cost. In recent years, low-field MRI has emerged as a potential solution to increase access to MRI, but at the cost of reduced signal sensitivity. This is a limiting factor in terms of resolution, traceable quantities of metabolites, and early detection of tumor tissue. In this context, hyperpolarization (HP) has emerged as the most promising technique to compensate for the sensitivity losses at low magnetic fields. HP can enhance signal intensity by >10,000 times, providing enough signal to image even species at low concentrations, such as metabolites internalized by cancer cells. Here, the first in vivo metabolic imaging methodology with hyperpolarization at low magnetic fields is proposed. The project involves the development of 1H and HP 13C MRI at low field, the study of enzymatic conversion from HP pyruvate to other metabolites, and in vivo metabolic tumor imaging in mice. Para-hydrogen-induced polarization (PHIP) will be used to generate the HP contrast agent. PHIP offers several advantages, including low costs, low instrumentation demands, rapid high-throughput, and scalable production of HP agents in the liquid state. The combination of low-field MRI with PHIP 13C has the potential to provide a method for early cancer detection in a low-cost scanner.

Mots clés : mri, nmr, hyperpolarization, 13c

Participants :
- Société Max-Planck pour le développement des sciences (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 189687.36 €
Projet GETQuantum (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

Understanding the dynamics of typical many-body quantum systems and the emergence of their universal thermodynamic description is both challenging and of paramount importance in various areas of physics, including condensed-matter and quantum-information theory, as well as statistical and high-energy physics. Combining methods of those fields into novel interdisciplinary approaches, GETQuantum - General Eigenstate Thermalization in Quantum Circuits - aims for establishing a General Eigenstate Thermalization Hypothesis (General ETH) and its connection to the mathematical field of Free Probability through the lens of Multi-Point Correlation Functions. The project focuses on Local Quantum Circuits, which, while native to quantum computing applications, have emerged as minimal models for many-body quantum dynamics and have let to unique analytical insights in recent years. Within this setting, the first scientific objective of this project is to identify universal properties of Multi-Point Correlation Functions and their dynamics. This includes deriving exact results obtained via novel analytical tools as well as by numerical investigations based on new efficient numerical algorithms. The second objective of GETQuantum is to establish the recently introduced General ETH, formulated in the language of Free Probability, and its consequences in interacting many-body quantum systems, modeled by Local Quantum Circuits, beyond the current paradigm of standard ETH. It aims at pinpointing correlations between matrix elements of physical observables and at confirming predictions of Free Probability by relating Free Cumulants, a central concept of Free Probability, with the dynamics of Multi-Point Correlation Functions. Hence, General ETH provides an intricate link between dynamical and statistical properties of many-body quantum systems. GETQuantum will deepen our understanding of universal aspects of their dynamics and vastly impact the fields mentioned above.

Mots clés : quantum chaos, eigenstate thermalization, quantum circuits, many body quantum dynamics

Participants :
- Société Max-Planck pour le développement des sciences (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 173847.36 €
Projet LNPscape (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Lipid nanoparticles (LNPs) are promising for RNA delivery, yet their effectiveness is hindered by endosomal entrapment post cellular uptake, limiting their therapeutic potential. The challenge lies in the inadequate understanding of the endosomal escape mechanism. This project aims to comprehensively replicate endosomal escape in vitro, employing three objectives to explore LNP interactions with membranes and RNA translocation. Objective 1 focuses on understanding the impact of pH and LNP formulation on LNP/membrane interactions. Employing supported lipid bilayers (SLBs) mimicking endosomal membranes, the binding and fusion rates of distinct LNP formulations will be examined using total internal reflection fluorescence microscopy. This will highlight key factors influencing these interactions, which constitute the initial step of endosomal escape. Objective 2 aims to reconstitute RNA translocation across endosomal membranes using giant unilamellar vesicles (GUVs). These vesicles simulate endosomal conditions, enabling the visualisation of LNP-loaded RNA translocation across vesicle membranes via spinning disk microscopy and fluorescence correlation spectroscopy. This will offer direct evidence of the success of the second step of endosomal escape and insights into how various LNP formulations react to diverse pH conditions. Objective 3 introduces novel bifunctional phospholipids (BPs) into LNP formulations to facilitate visualising LNP fusion with endosomes in live cells through confocal microscopy. This technique also permits the visualisation of RNA release and subsequent protein expression. By addressing the endosomal escape challenge through innovative in vitro and cellular models, this project aims to unravel the complexities of LNP interactions with cellular barriers. The findings have the potential to enhance LNP design, optimising endosomal escape mechanisms and ultimately improving their efficacy in gene delivery applications.

Mots clés : lipid nanoparticles, rna delivery, endosomal escape

Participants :
- Société Max-Planck pour le développement des sciences (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 173847.36 €
Projet ePSM (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Phosphorus (P) is one of the major essential macronutrients required for plant growth and food production. Crop yield on 40%~60% of the world's arable land is limited by P availability. However, due to the high fixation capacity of soil and inactivation of the applied phosphorus in soil, immobilization and precipitation results in scarcity of available phosphorus to plants. Using phosphate solubilizing microorganisms (PSM) to promote plant growth can be a promising strategy for sustainable food production in the future. However, many studies have indicated that the mechanisms seen in vitro do not translate into improved crop P nutrition in complex soil-plant systems. There are still some challenging questions needed to be answered before using PSMs as effective biofertilizers in soil conditions. State-of-the-art approaches like the high-throughput screening method and metagenomic analysis should be encouraged to facilitate the PSM’s application. This project aims at identifying and engineering phosphate solubilizing microorganisms and deciphering the mechanism of phosphate solubilization during plant-microbe interactions. For example, 1) use a high-throughput method to identify PSMs; 2) screen more than 3000 bacterial strains and 400 fungal strains to decipher their taxonomy evolutionary relationships and investigate the specificity of PSMs in solubilizing different insoluble phosphates; 3) use mutant libraries screen and metagenomic analysis to explore the phosphate solubilizing mechanisms. 4) investigate how plant root exudates influence microbiome assembly in P-limiting conditions; 5) optimize synthetic phosphate-solubilizing communities to promote plant growth (Arabidopsis thaliana, Lotus japonicas) and food production (Glycine max) in P-limiting soil. The outcome of this project will provide new insight into nutrient-mediated regulation of plant-microbe interactions and facilitates the development of biofertilizers in the field of nutrient supply.

Mots clés : microbiota, phosphate solubilizing microorganisms, metagenomic analysis, sustainable agriculture, food production

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

Fatty acids are essential metabolites used in biological cell wall formation, energy storage, and signal transduction. Fatty acid synthesis is carried out in an iterative sequence of reactions, conserved across all species. Yet different organisms have developed different solutions, the most impressive is the fungal fatty acid synthase (FAS). The 2.6 MDa molecular complex integrates all enzymatic functions required for the stepwise assembly of fatty acids. Its architecture is reminiscent of a chemical nanofactory: The enzymatic domains face the lumen of the barrel-shaped complex, where nascent fatty acids are transferred between active sites by an integral acyl carrier protein (ACP). The function of the fungal FAS has long been in focus of research, not only due to its elaborate architecture but also because it is ideally suited as a platform for synthetic biology. Fatty acid derivatives are ideal precursors to produce biofuels or fine chemicals; and fungi are well adapted for industrial applications. Advances in experimental structural biology have established a framework for the progression of the synthesis cycle. However, the driving element is the transport of reaction intermediates by the ACP which is inherently dynamics. Thus, structures alone are insufficient for a mechanistic understanding of the fungal FAS function. TRISAFA aims to close this knowledge gap by integrating advances in structural biology with molecular dynamics simulations to resolve the pace and regulation of the transport process in atomistic detail. This approach will address three hitherto unanswered questions: First, how are the transport dynamics coupled to the conformational dynamics of the FAS? Second, how is the pace of the transport regulated? And finally, what factors determine termination of the fatty acid synthesis cycle. Ultimately, this project will yield a complete model for the progression of fatty acid synthesis, pivotal to their exploitation for biotechnological applications

Mots clés : computational biophysics

Participants :
- Société Max-Planck pour le développement des sciences (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 173847.36 €
Projet SpongeMetabOxygen (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : SIGNED

Sponges are considered to be one of the most ancient lineages of metazoans and are believed to have emerged amongst these early branching animal lineages at a time before the oceans became fully oxic around the middle to late Neoproterozoic Era (850-542 Mya). Sponges appear to retain some sort of ancestral memory of the hypoxic milieu from which they evolved and can still tolerate harsh hypoxic or anoxic conditions for relatively long periods. They express specialized anaerobic pathways that have been mostly lost in higher order animals such as fish and mammals, and yet remnants of these pathways persist primarily in the way they use the endogenously generated gases hydrogen sulfide and nitric oxide (NO) as signaling molecules for cellular homeostasis or as key players in cytoprotection during periods of hypoxic stress. Extensive sequencing of sponge microbiomes has primarily demonstrated the ubiquitous presence and expression of sponge symbiome pathways involved in NO generation via ammonia-oxidation and denitrification as well as the oxidation of reduced sulfur compounds, hinting at an active anaerobic lifestyle within sponges. Experimental demonstrations of these processes are rare in sponge holobionts and lacking in sponges sensu stricto who also express the relevant anerobic energy metabolisms. I will thus aim to demonstrate, disentangle, and integrate sponge holobiont metabolisms along the oxic-anoxic continuum by combining my expertise in sponge holobiont biogeochemistry and metabolic pathways with the expertise of the host in sponge physiology, nano-oxic O2 measurements at multiple spatial scales and dimensions, and advanced bioimaging techniques. The proposed multimethod and interdisciplinary study will thus provide an unprecedented view of sponge holobiont metabolism at the thermodynamic limit of animal life thereby providing further insights into higher animal responses to hypoxia and the future of animal life on a planet experiencing ocean deoxygenation.

Mots clés : sponges anaerobic energy metabolism hypoxia anoxia oxygen host symbiont interactions hydrogen sulfide sulfur oxidation nitrite reduction nitric oxide ammonia oxidation denitrification

Participants :
- Université du Danemark du Sud (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 247553.28 €
Projet VegArch (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Amid today’s environmental challenges, the long-standing Western divide between nature and culture is increasingly being called into question. Roman Antiquity, a significant period in our past, helps us reconsider such opposition. For the Romans, maintaining a harmonious relationship with ‘nature’ was essential to sustaining order and prosperity, as it was not a mere physical environment, but a subversive force, a realm intertwining the sensory with the divine. The use of real and iconographic vegetation in the living spaces was a central concern. The VegArch project aims to explore this vegetalisation within the specific context of Gallo-Roman sanctuaries of the 1st-3rd c. AD. From the penetration of Italic traditions to an unprecedented ‘hypervegetalisation’ of architecture, this greening has long been explained by a presumed persistence of Celtic naturalism or a mere decorative trend. Its role in shaping the experience of nature, the cosmos, and the divine can now be addressed with the expanding archaeological data and ecofacts and through an interdisciplinary approach. The vegetal forms will be gathered and compared in a trans-medial analysis, considering real and artificial forms as one and the same vegetal art and the sanctuary as a unitary system. This formal step will highlight the specificities of Gallo-Roman contexts in a global/local perspective. Through comprehensive and contextualised case studies, the vegetal forms will then be analysed in their spatial, temporal and sensory dimensions to reveal their polysemic value and how they engage the senses and shape the experience of the sacred. The resulting synthesis will contribute to the cultural history of vegetalisation of Western architecture, helping to unveil the relationship with nature in ancient societies, questioning our own practices and beliefs. The VegArch project, for which ENS is the ideal institution, will open numerous new perspectives and foster long-term European collaborations.

Mots clés : gaul, sanctuaries, roman gardens, architecture, vegetalisation, d cor, vegetal ornament, iconography, ecofacts, relationship with nature, architectural sculpture, mosaic, painting, stucco, plant

Participants :
- École normale supérieure PSL (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 226420.56 €