Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet Asymmetric fates (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The haematopoietic system relies on the potential of haematopoietic stem cells (HSCs) to self-renew and differentiate into all lineages of mature blood cells, and is a reference model to study differentiation hierarchies. Cell fate determination results from different layers of regulation, including transcriptional, translational, epigenetic, metabolic, and cell biological changes. Degradation pathways, such as autophagy and the proteasome, play mechanistically relevant roles that in principle may impact on all these layers. Indeed, catabolic degradation results in the building blocks necessary for anabolic processes, while it also preserves stemness and regenerative potential. Asymmetric cell division (ACD) has been extensively reported to contribute to maintenance of stemness by the rise of daughters with divergent fates in stem cells, including HSCs. Taken together, I postulate that degradation pathways work synergistically to give rise to the asymmetric fates observed in HSCs differentiation and can be targeted for future therapeutic use in humans. I plan to test this by 1. establishing an efficient strategy to image asymmetric inheritance of cargo by long-term ex vivo HSCs expansion, 2. verifying whether autophagosomes and proteasomes are co-inherited in HSCs mitoses, and 3. assessing the impact of cargo segregation by ACD on HSC maintenance and differentiation. I will use state-of-the-art techniques and novel murine models to assess the molecular and cell biological mechanisms of ACD modulation on HSC maintenance, relying on imaging of known and potentially novel components that are asymmetrically inherited by HSCs and able to impact their fate determination. Finally, I will further evaluate the in vivo impact of cargo inheritance on haematopoiesis by using single-cell transplantation. The knowledge derived from this project will potentially boost the development of novel regenerative medicine therapeutic approaches.

Mots clés : autophagy, proteasomes, degradation, fate determination, stemness

Participants :
- University of Oxford (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €
Projet Forgery (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

The high-stakes game of forgery, from priceless art to counterfeit banknotes, has stimulated public and professional interest for centuries. This project adds to the body of relevant examples, and feeds back into the broader theoretical frameworks, by looking at a number of texts which appeared for the first time in 17th- and 18th-century Scandinavia and were revealed to be forgeries. The most famous (although still relatively unknown) are ‘Hjalmars och Hramers saga', ‘Krembre saga' and ‘Hafgeirs saga Flateyings'. Since their appearance very little research has been done on these works: as literary forgeries they are deemed to have little value in the intellectual and literary history of Scandinavia. This project will prove, on the contrary, that these texts play a central role in the development of literary and philological studies in the region. Moreover, their very existence problematises many of the basic concepts employed by researchers of Scandinavian texts: fiction, history, philology, textual unity, authorial intention and not least national identity. While the overall aim of the project is to bring the importance of these forgeries to light, this will be carried out through three subsidiary aims: 1) Studying the interconnectedness of philological developments with developments in forgery. As forgers develop new techniques, philologists do so too in order to expose fakes, but these dialectical movements are not just opposites, but may also involve a blurring of techniques and aims. 2) Looking into the ways in which international trends have fed into Scandinavian forgery, taking classical and renaissance cases of forgery and forgery exposure as well as enlightenment and romantic causes celebres. 3) Analysing forgery as national fantasy, by using the ideosyncrasies found in forgeries to glimpse the aspirations and interests of both producers and consumers, seen as representative of certain culture-specific desires.

Mots clés : forgery authenticity saga philology scandinavia 17th century 18th century

Participants :
- University of Gothenburg (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 173857.2 €
Projet PiezoSpin (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

The holy grail of magnetic storage research is the discovery of novel all-voltage controlled magnetic metamaterials that enable to develop a universal memory device that simultaneously meet high-power-efficiency and ultra-high storage capacity. Antiferromagnetic (AFM) materials could represent the future of spintronic applications as a result of the numerous interesting features they combine, e.g. they are robust against perturbation due to magnetic fields, produce no stray fields, display ultrafast dynamics and are capable of generating large magneto-transport effects. However, the truly distinctive feature posed by AFM materials when compared to ferromagnetic ones is its modulated magnetic order, which is marginally exploited in spintronics applications. The PiezoSpin project seeks to demonstrate a novel proof-of-concept for an innovative universal ultra-high power-efficient AFM-based spintronics memory device, which has the potential for transforming the ferromagnetic-dominated magnetic data storage technology. We will produce hybrid FeRh-based alloy/ferroelectric (FE) heterostructures, where the FeRh-based alloy overlayer will act as a resistive-switch driven by the FE underlayer acting as a voltage-controlled actuator. We will investigate the strain-dependent electrical resistivity of the FeRh-based alloy on the applied voltage. This piezo-magnetoresistivity effect will be optimized by chemical doping of the FeRh-based alloy to maximize that strain-dependent resistivity change at room temperature. This novel hybrid device concept exploits the strain-dependent giant magnetoresistance that appears in spin-orbit coupled (anisotropic) AFMs. Its origin resides in the superzones band-gap effect as a result of the onset of modulated magnetic order. Such piezo-magnetoresistivity effect is shared by numerous AFMs, opening up a new research field, i.e. AFM-based strain-electronics, where the material combinations and functionalities to explore are immense.

Mots clés : antiferromagnets, bulk like giant magnetoresistance, spintronics, nanomagnetism, straintronics, memory devices

Participants :
- University of Leeds (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet GallBiome (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The human gastrointestinal tract harbors a complex community of microorganisms that confer metabolic, immunological and neurological benefits to the host. This assemblage is known as the Gut Microbiome and has received increased attention over the last decade. Scientists have begun to uncover the importance of these bacterial inhabitants and expand investigations to consider how site-specific microbiomes affect host physiology. While more than one million cholecystectomies (gallbladder removal surgeries) are performed throughout Europe each year, the bacterial communities associated with the human gallbladder and its disease states remain unknown. Studies are lacking that characterize the effects of cholecystectomies on the gut microbiome. Without the ability to regulate bile entering the duodenum during food intake, it is expected that gallbladder removal will lead to downstream changes in the intestinal population. Here, the microbial composition of human bile, gallbladder mucosa, and biopsies of surgically removed healthy gallbladders (adherent and non-adherent microbiota) will be investigated using 16S rRNA metagenomics. The profiles will be compared to samples of a second cohort undergoing emergency cholecystectomies, in order to identify possible biomarkers for gallbladder disease. Once the gallbladder microbiome has been elucidated, the impact of its removal on the gut microbiome will be assessed. Using molecular and cultivation based techniques, on stool samples (collected during the recovery period) and analyzed for community composition, metabolomics, bile, fat and energy content. GallBiome will form the basis for establishing relationships between gallbladder microbiota, gut microbiota, and human health with a view to informing future development of diagnostics and therapeutics. Ultimately, characterization of the core gallbladder microbiome has important biological and medical implications with potential to lower the risk and incidence of cholelithiasis.

Mots clés : gallbladder, microbiome, biomarkers, health, disease

Participants :
- Teagasc - The Irish Agriculture and Food Development Authority (Irlande) — Coordinator, beneficiary, Recherche, subvention : 187866.0 €
Projet DIMEvAR (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The human gastrointestinal tract harbors trillions of microbes, known as the gut microbiota. This microbial community helps modulating developmental, immunological, and metabolic functions of the human host and it plays an important role in medicinal drug response. Several works showed the bidirectional relationship between the gut microbiota and drugs. Medication modifies microbiome composition both in vitro and in the human gut. Further, commonly used drugs influence the microbiome metabolic functions and increase the abundance of antimicrobial resistance (AMR) genes in human cohort studies, suggesting that non-antibiotic drugs could contribute to the emergence of AMR. At the same time, microbiome-encoded enzymes can metabolize a wide range of medical drugs, participating in both beneficial and adverse effects. Considering that many drugs are used over extended periods of time to treat chronic diseases, long-term exposure to drugs may likely drive microbiome evolution. This could influence and evolve metabolic properties of gut microbes and lead to the emergence of novel AMR. This project aims at better understanding the impact of long-term exposure to medical drugs on human gut microbiome evolution at the phenotypic and metabolic level, the underlying molecular mechanism, and their consequences in vivo. Based on previous data and in analogy to well-understood antibiotics, I hypothesize that non-antibiotic drugs might induce stress-triggered microbial evolution. The project follows three specific objectives: (i) Quantify the impact of drug-induced evolution on microbiome metabolism and antibiotic sensitivity; (ii) Determine the role of bacterial stress responses in microbiome evolution; (iii) Assess drug-induced microbiome evolution using gnotobiotic mouse models. If successful, this work will reveal the molecular mechanisms underlying microbiome-drug interactions and pave the way for their rational modulation to improve current and future drug therapies.

Mots clés : gut microbiome, microbiome evolution, antimicrobial resistance, bacterial mutagenesis, drug metabolism

Participants :
- European Molecular Biology Laboratory (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 262209.6 €
Projet TRISCPOL (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The human genome is composed of 3 billion base pairs of DNA that are replicated prior to every cell division with an astonishing accuracy. High-fidelity replication is necessary to maintain genome stability, and hence to avoid premature ageing and cancer. This project aims at understanding the role of the iron-sulphur (FeS) cluster in human DNA polymerase delta (Pol δ), one of the major replicases. FeS clusters are ancient and versatile co-factors that are commonly known for their function in electron transport in the mitochondrial respiratory chain. In recent years, a surprising number of proteins involved in DNA metabolism have been discovered to contain an FeS cluster including all replicative DNA polymerases in yeast. While the requirement of an FeS cluster for the function of replicases was demonstrated, the actual role of the FeS cluster in these enzymes has remained largely elusive. The TRISCPOL project aims to: 1) Confirm and characterise the FeS cluster in human Pol δ by using iron incorporation assays, UV-visible and electron paramagnetic resonance spectroscopy. 2) Determine the role of the FeS cluster in human Pol δ in vitro. Purified Pol δ will be subjected to oxidative stress conditions, and then changes in structural and functional features will be measured. A combination of techniques including deuterium-hydrogen exchange mass spectrometry, as well as DNA binding, DNA synthesis, processivity and fidelity assays, will be employed. 3) Define the role of the FeS cluster in human Pol δ in vivo. Mutants in the FeS cluster-binding region will be engineered and tested for their ability to functionally complement cells depleted of endogenous Pol δ. Unveiling the role of the FeS cluster in human Pol δ will shed new light on the principle of eukaryotic DNA replication. Moreover, this knowledge will contribute to our understanding of the molecular basis of cancer and may eventually allow the development of novel strategies of treatment.

Mots clés : dna polymerases, iron sulphur cluster, dna replication, genome stability

Participants :
- University of Zurich (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187419.6 €
Projet Gut-InflammAge (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The human gut hosts a large and diverse ecosystem of microbes termed the gut microbiome. Microbiome imbalances, often affecting the interplay of the microbes with the host immune system, have been linked to a variety of diseases. Being amenable for modulation, for example via diet and probiotics, the gut microbiome is a potential target of high interest for promoting human well-being. Since the proportion of Europeans above 65 is expected to double from 2010 to 2050, healthy aging is an important issue on the European policy agenda. Aging has been linked to an enhanced pro-inflammatory status, and many age-associated diseases involve inflammation. Changes in the taxonomic composition of the gut microbiome with age that associate with increased frailty among the elderly have been described. However, the evidence is still limited and possible interventions remain to be explored. Moreover, changes in the pro-inflammatory potential of gut microbes can occur without coinciding compositional changes of the microbiome. To address these issues, we propose an approach combining high-throughput sequencing, immunoglobulin A-based cell sorting, microscopy, and bioinformatics to explore differences in the composition and pro-inflammatory potential of the gut microbiome of young and older Danish individuals. Using mouse as model system, we will further explore whether a periodic fasting scheme with established metabolic health benefits when applied from middle to old age promotes gut microbiome modulations. The project will be supervised by associate professor Manimozhiyan Arumugam at the Center for Basic Metabolic Research (CBMR, University of Copenhagen). CBMR excels in research on the impact of the gut microbiome on metabolic and inflammatory disorders. This environment of expertise as well as access to human microbiome samples with associated information on health status will be a key asset to this project.

Mots clés : gut microbiome, inflammaging, healthy aging, inflammation, metabolic health, immunoglobulin a, dietary restriction, autophagy, metabolism

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 200194.8 €
Projet ACtIVAtE (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The human pathogen Acinetobacter baumannii represents a deadly threat to human health. Despite its established clinical relevance, the pathogenicity of this nosocomial superbug is poorly understood. The biphasic amoeba Acanthamoeba castellanii is a cellular infection model broadly used to decipher the virulence mechanisms of human pathogens, as bacterial resistance upon amoebal predation (grazing) are often correlated with their pathogenicity potential in human. However, high-throughput screening approaches to investigate the virulence mechanisms of A. baumannii using this amoeba in an infection context are still lacking. This project aims at applying original large-scale screening approaches to identify A. baumannii virulence factors using the amoeba A. castellanii as host-pathogen system. The proposed experimental set up allows monitoring the outcome of the bacteria-amoebae interactions in qualitative and quantitative manners, at both population and single cell levels. Virulence induction of A. baumannii, as well as the use of successful clinical isolates will be tested using several complementary grazing assays. Precise localization of A. baumannii reporter strains will be done on both trophozoite and cyst stages of A. castellanii, complemented with (i) real-time and live-cell fluorescence imaging as well as (ii) electron microscopy techniques. Viability assays for both bacteria and amoebae will be done to understand the symbiotic outcome of this interaction. The global resistance potential of A. baumannii will be assessed by (i) Tn-seq analysis and (ii) high-throughput screen of individual mutant strains, followed by in depth mechanistic studies on validated attenuated strains. This project will shed light on the yet unknown global virulence mechanisms of A. baumannii by generating original screening methods using A. castellanii as an infection cellular model.

Mots clés : host pathogen interactions, high throughput screening approach, human pathogen, virulence factors, pathogenicity, gram negative bacterium, amoeba, macrophages, epithelial cells

Participants :
- University of Namur (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 172800.0 €
Projet EPOFFSPRING (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The idea of transmitting paternal environmental impact across generations has been indicated and described in studies across species, but the mechanism is still unclear. The overall aim of the project is to test whether H3K27me3, a type of epigenetic modification on histone 3 [1], is involved in transmitting environmental impact across generation to influence the behavior of offspring. With a behavioral neuroscience background, the experienced research (ER) will apply his expertise in high throughput behavioral assay and combine techniques he will learn from the host lab, including epigenetic profiling, NGS, targeted epigenome editing and computational analysis to address specifically whether paternal drug experience influence offspring behavior via modifying H3K27me3 on dopamine-related genes that are involved in various behaviors [2]. Besides advancing our understanding of the importance and mechanism of paternal inheritance and the role of epigenetics in general, this project will also further extend zebrafish as a model in studying cross-generational transmission of environmental experience by combining multidisciplinary techniques. The trainings ER will be beneficial and essential for his future goal to study epigenetic mechanisms underlying physiology and pathology of brain.

Mots clés : epigenomics, zebra fish, trans generational epigenetic inheritance

Participants :
- University of Birmingham (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet MegaScapes (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

The idea that Europe’s Atlantic façade shares elements of a common culture rooted deep in prehistory has long fascinated geographers and archaeologists, and finds expression in modern political organisations such as the Atlantic Arc Commission. The MegaScapes project will use the latest statistical and quantitative methods to examine whether the explosion of megalithic construction across Europe’s Atlantic façade between 5000-2500 BC (and especially 4500-3500 BC) provides evidence of a shared understanding across distant regions of the Atlantic European seaboard as long ago as the Neolithic. It will undertake a comparative study of four important micro-regions of megalithic construction spanning the United Kingdom, Ireland, France and Spain, which will use advances in computational and spatial statistical modelling to analyse spatio-temporal patterns in the arrangement of megalithic monuments, and their possible meaning in a wider landscape context. The latter will be inferred by rigorously investigating regularities in the geographical placement of megaliths, trends in their visibility, their association with pathways and their relation with the lived environment such as settlement and land use. Ultimately the core aim of MegaScapes is to investigate whether the spatial meaning of Neolithic megalithic architecture was regionally variable, or whether it was indeed shared along the Atlantic European seaboard.

Mots clés : megalithic complex, spatial analysis, computational modelling, landscape archaeology, site, predictive modelling, point pattern analysis

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €