Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet ProphARG (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

In the European Union, 25,000 deaths per year are caused by multidrug resistant bacteria. This trend is predicted to increase with ever increasing misuse and overuse of antibiotics, which accelerates the evolution of antibiotic resistance (AR). An important mechanism of transferring antibiotic resistance genes (ARGs) among bacteria are temperate bacteriophages (prophages), viruses that can incorporate their own genetic material into the bacterial chromosome, thereby providing their bacterial host (which is now called a ‘lysogen’) with additional genes, such as ARGs. Despite their vast abundance in nature, our understanding of the evolution of ARG-carrying prophages is still incomplete. Therefore I will study the evolution of ARG-carrying prophages and their host bacteria. Specifically, using constructed lysogens (carrying prophage lambda+ARG) of E. coli bacteria, I will (1) use competitive fitness assays to determine the costs/benefits for bacteria of carrying prophages that encode AR and how these costs depend on environmental antibiotic concentrations and the frequency with which the prophage enters the lytic cycle (i.e. the prophage becomes active, replicates and lyses the host cell). (2) I will follow the evolution of these lysogens that carry AR-encoding prophages using a serial transfer experiment in the presence/absence of antibiotics and compounds that induce phage lysis. (3) I will sequence the evolved lysogens including their prophage genomes to detect underlying genomic changes associated with bacterial adaptation to prophage carriage. I predict that the net effect of a prophage that encodes an ARG on the growth and evolution of its host bacterium will strongly depend on both the frequency with which the phage enters the lytic cycle and the costs/benefits of the ARG. By using a novel approach that has been neglected so far (evolution of ARG-carrying prophages) this project will improve our understanding of AR evolution.

Mots clés : experimental evolution, temperate phages, antibiotic resistance

Participants :
- Board of the Swiss Federal Institutes of Technology (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187419.6 €
Projet FBXW7-InReg (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Inflammatory bowel disease (IBD) is a severe disorder affecting millions of people in Europe, characterised by chronic flares of intestinal inflammation and causing tissue loss or malfunction. Currently, the available treatments can only reduce symptoms. New regenerative therapies promoting epithelial functionality are highly needed. Several studies report how upon damage, progenitors or more committed cells re-acquire stemness properties and foetal-like signatures to restore intestinal homeostasis. However, it is still unclear how such regenerative response is modulated and how cells revert to their adult state. Preliminary data from the host lab indicate that loss of expression of FBXW7 protein, member of a E3 ubiquitin ligase complex, reinforces cells in the foetal-like state. Interestingly, FBXW7 mutations are under positive selection in IBD patients. Thus, I propose that upon injury, cells lacking FBXW7 maintain a foetal-like state, where they are refractory to terminal differentiation, increasing the risk of aberrant tissue restoration. To test my hypothesis, I will exploit state-of-the-art in vivo and in vitro models of intestinal regeneration and make use of forefront technologies, such as CRISPR, high-content imaging, mass spectrometry and single cell RNA sequencing. This will allow me to 1. characterise FBXW7 impact on intestinal regeneration, 2. define FBXW7 mode of action in human intestinal cells, and 3. identify FBXW7 substrates as potential targets to restore tissue homeostasis. By addressing these points, it will be possible to obtain key insights into the mechanism of intestinal regeneration and identify ways to efficiently induce and control tissue repair in IBD patients, avoiding the expansion of unrestrained proliferating foetal-like cells. Importantly, leading this action, I will acquire a new set of technical and transferrable skills and reach a deep scientific maturity that will grant me a successful career as future group leader.

Mots clés : intestinal epithelium, regeneration

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 207312.0 €
Projet PARPinhibit (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Inhibition of PARP1 in cancer therapy is a recently adopted strategy to treat cancers where DNA repair is defective, such as breast and ovarian cancer caused by mutations in BRCA1 or BRCA2. In addition, PARP1 inhibitors (PARPi) can be useful even in the absence of BRCA mutations, likely due to pathogenic variants or epigenetic inactivation of other DNA repair related genes. However, development of resistance to PARPi is a significant challenge. To address this challenge, I propose to identify proteins that modulate PARP1 activity that could be used as additional therapeutic targets. The strength of this project is based on a systems biology overall strategy exploiting multiple independent datasets to identify candidates protein interactors, followed by a rigorous biochemical and genetic approach to characterize this interaction. Analysis of identified proteins and their role in PARPi resistance will be achieved at three main levels: a) in-silico and molecular studies of the interaction; b) influence on PARP1 activity and role in PARPi resistance after CRISPR-cas9 editing; c) expression levels in breast and ovarian cancer tissues. Results from this project will illuminate mechanisms of PARPi resistance and generate potential targets for therapy in breast and ovarian cancer. These results will contribute to the reduction in mortality due to breast and ovarian cancer and they will give an answer to this world-wide diffuse challenge.

Mots clés : drug response and, or resistance, breast and ovarian cancer, parp1

Participants :
- Moffitt Cancer Center (Etats-Unis) — Partner, organization partner, Recherche, subvention : 0.0 €
- National Research Council (Italie) — Coordinator, beneficiary, Recherche, subvention : 251002.56 €
Projet TRIAGE (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Inland waters are an integral component of the carbon cycle as they process, store, transport, and emit significant amounts of carbon. Freshwaters emit carbon in the form of carbon dioxide (CO2) and methane (CH4), both important greenhouse gases (GHG). Lakes subject to a high nutrient load in a process called eutrophication are typically characterized by enhanced primary production and depleted oxygen, variables directly related to GHG production. Therefore, with increasing nutrient load (i.e., trophic state), lakes have the potential to substantially impact GHG emission, but the relationship is poorly constrained. Climate change-induced variations in variables such as temperature and precipitation could alter nutrient loading, primary production and oxygen, which in turn could change the GHG balance of a system. Evidence suggests that lake eutrophication and climate change impacts interact and alter the lake GHG budget in non-linear ways. Moreover, eutrophication may shift the balance toward higher emissions of CH4, a more potent GHG. To date, very few studies have used a systematic approach to understanding the interaction between GHG emissions and eutrophication, which is essential for efficient management of inland waters, particularly in the face of global change. The overall goal of the project is determine how the GHG balance of aquatic systems shift along a trophic gradient and what some of the drivers of these shifts may be. The project will consist of a multi-lake survey throughout central Europe across a large trophic gradient, followed by modeling of the full GHG balance of those lakes and testing of the strength of relevant drivers. Constraining the variables that dictate the GHG balance will help to inform better management practices for mitigating climatic impacts on aquatic systems as well as allow for the development of models capable of predicting the response of aquatic systems to global environmental changes.

Mots clés : limnology, aquatic systems, carbon cycle, methane, eutrophication

Participants :
- University of Geneva (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187419.6 €
Projet InnoMarket (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Economic Sciences
Statut du projet : CLOSED

InnoMarket is opening the black box of the international road freight transport market, which is organized as a bazaar. The project will investigate this 'institutional order' of road freight transportation that leads to unintended inefficiencies such as less than full truck loads. The objective is firstly to identify innovative potentials for lowering cost and increasing sustainability by analyzing practices of overlapping markets and built-in controversies in the transport chains. Secondly, the project aims at closing a gap in transport research by explaining the low implementation rate of (existing) innovations. Theoretically, the project builds on market making literature and the socio-technical view of innovation processes. An ethnographic action net study is applied to investigate the overlapping markets and international inter-sectoral transport chain actors; the industrial shipper, customer, intermediaries, transporter and drivers. The study involves 50 interviews in Poland, Denmark and Sweden and “shadowing” actors. The results of the study is a novel perspective on how road transport markets work, contributing to knowledge of transport-chain efficiency, sustainability and innovation that is needed in EU as well as in other parts of the world. CBS research expertise in transportation, constructivist market theory and ethnography advances the fellow in research, methodology and publication. CBS Business-in-Society activities advance the fellow in dissemination; public podcasts; practitioner workshops, and publications. Host professor supervises in transport and logistics research, in workshop method, publication and editorship skill. Secondment at ITD/International Transport Denmark´s innovation center offers training-in-innovation projects. Fellow research profile is broadened, including organizing, transportation expertise, ethnographic action net methods, publishing, outreach experience, and an international network of academics and non-academics.

Mots clés : organizing, action net, road freight transportation network, market making, innovation, low costs, sustainability, ethnographic methods

Participants :
- Copenhagen Business School (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212194.8 €
Projet SSAR (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Insect pests are very damaging to worldwide food production, and there is a great demand for new environmentally-friendly bio-pesticides. Saponins are a structurally diverse class of naturally occurring plant defense compounds that are a promising resource for novel and more sustainable pesticides. Due to their detergent-like properties, saponins can disrupt the cell membranes of herbivory pests, cause cell death, and ultimately kill them. Despite the promising potential of saponins as bio-pesticides, little is yet known about which saponin chemical structures are toxic to which specific pest. The SSAR project aims to elucidate the relationship between saponin chemical structures and their biological activities and evolution. First, the genes involved in the biosynthetic pathway of saponins will be identified. Then desired or novel saponins will be produced in plant tissues through metabolic engineering with the identified genes. Finally, purified saponins will be used in bioassays with a range of pest species, to unlock the code of exactly which saponin chemical structures have a given specific biological activity. The new knowledge gained will have great industrial application potential as a generic platform for the production of bioactive compounds from plants and their use for bio-pesticides as an alternative to chemically produced pesticides. The new bio-pesticides will both help to meet society’s need for more sustainable food production and to contribute to the development of the knowledge based bio-economy. Identification of genes involved in saponin biosynthetic pathway will also open the possibility to engineer and breed crop with tailored saponin-based pest resistance capabilities. The SSAR will allow me to develop as an independent and mature researcher, and extend my expertise in both academic and non-academic sectors through the training in the host institution and the collaboration with a bio-pesticide and generic agrochemicals innovative company.

Mots clés : metabolic engineering, plant defense, evolution, structure activity relationships, triterpenes

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212194.8 €
Projet MADMpancreas (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Insulin producing beta cells are derived from bipotent pancreatic progenitors (bi-PPs) that constitute the primitive ductal epithelium. While we now know a great deal about the transcriptional networks required for endocrinogenesis and commitment to the beta lineage, considerably less is understood about the cellular events that initiate delamination and activate differentiation networks. The host group recently found that ligand-specific Egfr signaling is essential for these processes. Signaling by the highly potent Egfr ligand betacellulin diminishes apicobasal polarity leading to upregulation of Ngn3, delamination, and beta cell differentiation. The overall aim of this proposal is to elucidate the role of Egfr signaling in the beta cell differentiation process. I will ask: Is the seemingly stochastic differentiation of bi-PPs regulated by inherent differential Egfr signaling? Do quantitative differences in this single pathway lead to different cellular outcomes? How does the targeted loss of Egfr in Ngn3-expressing endocrine precursors affect their differentiation? What are the genes regulated by Egfr pathway activation that putatively commit Ngn3+ progenitors to a beta cell fate? And how does the disruption of endocrine differentiation affect ductal morphogenesis? Answers to these questions have remained elusive because of the difficulty of observing individual cell behaviors in situ in the developing pancreas. To meet this challenge, I will adapt the cutting edge mouse genetic tool Mosaic Analysis with Double Markers (MADM) to quantitatively manipulate Egfr levels in bi-PPs and to concomitantly label altered cells. The successful implementation of MADMouse will deliver findings of immediate interest to investigators seeking to improve the directed differentiation of therapeutic grade beta cells from hPSCs. I will augment my expertise in precision mouse genetics with training in hESC culture enhancing my career goal of establishing my own research group.

Mots clés : beta cells, egfr, pancreas, morphogenesis, tubulogenesis, directed differentiation, diabetes, madm

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 207312.0 €
Projet Forests and CO (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Intact forests harbor large amounts of carbon and unique biodiversity, suggesting that protecting forests may benefit climate change mitigation and biodiversity conservation alike. Yet, forests also provide other essential services, from timber to energy to recreation. Balancing these multiple, sometimes conflicting objectives requires understanding trade-offs and synergies among them. A key question in this context is whether schemes to maintain or increase carbon stocks through forest management actually co-benefit biodiversity. Although frequently promoted, assumptions about such co-benefits have not been rigorously assessed. Forest and CO will test whether policies designed to protect either biodiversity or carbon in Europe’s temperate forests are synergistic or conflicting. Three work packages (WP) will focus on both unmanaged, old-growth forests, representing a baseline for key ecosystem functions, and managed forest, constituting the majority of Europe’s forests. WP1 will build a network of forest researchers to gather existing data on old-growth forests in Europe, and create the first map of their distribution. WP2 will use plot-level data to model the relationship between forest biodiversity and carbon storage, and assess whether this relationship differs between old-growth and managed forests. WP3 will test whether carbon/biodiversity co-benefits vary, when scaled up to broader extents, using satellite products and vegetation-plot databases. This action will provide new insight into the synergies and trade-offs between carbon and biodiversity in temperate forests and develop methods to map these trade-offs. Scientifically, this will contribute substantially to the fields of forest ecology, conservation science, and sustainability science. From a policy perspective, Forest and CO will help to tailor forest management options to jointly foster carbon and biodiversity, thereby contributing to key policy goals on curbing climate change and biodiversity loss.

Mots clés : biodiversity conservation, carbon sequestration, diversity patterns, ecosystem services, european vegetation archive, meta analysis, old growth forest, sustainable forest management

Participants :
- Humboldt-Universität zu Berlin (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 159460.8 €
Projet INTEGRATE (Horizon 2020, appel à projets 2019)
Action : Cofund Doctoral programme
Statut du projet : SIGNED

Integrated Genomics Research Centre

Mots clés : genomics, data science, human health, precision medicine

Participants :
- National University of Ireland (Irlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 2169600.0 €
Projet Dommigs (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

Interferometry is a universal, precision metrology tool. Matter wave interferometers have been developed over the last decades and are now used as gravimeters for prospecting and geoscience and in fundamental studies, i.e. of quantum coherence, gravitational constant measurements and dielectric response. Research is ongoing for use as accelerometers for long distance, under-water navigation and for dark matter and gravitational field exploration in space. Monolithic interferometers, where diffraction slabs are cut into a single crystal, are particularly attractive in the latter contexts due to their unsurpassed thermal and mechanical stability. However, up till now no monolithic interferometers for atoms have been realised, because atoms cannot penetrate the diffraction slabs. This project presents a completely new idea: A reflective monolithic atom interferometer with reflective slabs cut into a silicon monolith. Two configurations are considered: i) Surface Diffraction: Scattering at the intermolecular potential of Si(111)-H(1x1) (can be used with light atom beams only) and ii) Quantum diffraction: scattering at the dispersion potential from a blazed grating (can be used with all atom beams). The aim of this project is to provide a theoretical model of the new interferometer based on realistic experimental conditions and use the model to evaluate the new instrument for dark matter/gravitational waves exploration, prospecting and navigation applications. The project connects interdisciplinary expertise - the applicant Dr. Fiedler, expert on the theoretical description of matter-wave optical devices, Prof. Holst, expert on matter wave instrumentation, machine learning expert, Ass. Prof. Parviainen and theoretical particle physicist Prof. Kersten. The applicant will learn machine learning techniques, while improving several transferable skills, including scientific and grant application writing, open data and research management and science communication skills.

Mots clés : matter waves, quantum reflection, dispersion forces

Participants :
- University of Bergen (Norvège) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 202158.72 €
Projet SURDIM (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : TERMINATED

International immigration is a scarcely studied phenomenon in rural Europe, even immigrants may prevent depopulation and ageing in rural areas. Filling this gap, the project studies the role of international immigrants in supporting local economies, bringing in new ideas on sustainability and revitalising the social fabric of Pyrenean municipalities with fewer than 2.000 inhabitants in four areas with contrasting economic structures in France and Spain. In line with Horizon 2020, the project helps to identify major economic opportunities for innovative companies and contribute to the Union´s competitiveness and employment in rural areas. The research objectives are: 1) conduct a critical theoretical exercise of international immigration in rural settings; 2) analyse immigrant pathways of labour/economic incorporation in selected French and Spanish Pyrenean municipalities to identify sustainable economic projects managed/supported by immigrants, and present successful experiences in terms of rural development; 3) study settlement processes of immigrants in selected municipalities, analysing challenges for social incorporation in rural communities, and exploring issues on well-being and inter-cultural aspects; 4) continue updating and extending to other parts of Spain and France the existing Geographical Information System (GIS) in order to contribute to policy and societal debates on immigration in rural areas. Objective 1 will be achieved through comprehensive desktop research to collect and analyse scientific and policy literature relevant to locate pertinent concepts and theoretical frameworks. O2 and O3 will be attained through primary qualitative data analysis collected in semi-structured interviews with immigrants and key informants, and complemented with participant observation. Through statistical compilation and fieldwork for O2 and O3, statistical data and photo material at a local level will be incorporated into an open-access GIS (O4)

Mots clés : international immigration, rural development, immigrant enterpreneurship, pyrenees, farming, rural, tourism, sustainability

Participants :
- Autonomous University of Barcelona (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 172932.48 €