Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet MEMDYN (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The alternating access model of how membrane-embedded transport proteins translocate substrates across biological membranes has been proposed since the 1960s: membrane transporters bind substrates on one side of the membrane and release them on the other side upon conformational rearrangements in the protein. This has been experimentally confirmed by high-resolution structures of membrane transporters in different conformations and is exemplified by the conformational change in the archaeal glutamate transporter homologue GltPh from Pyrococcus horikoshii. GltPh is a trimer in which each protomer functions independently of the others. Outward and inward facing conformations suggest transport by alternating access to either side of the membrane whereby a distinct transport domain undergoes large rotational and translational movements relative to the static trimerisation domain. It is unknown how GltPh achieves this conformational rearrangement, which occurs both in the absence and presence of substrates. We propose to integrate cutting-edge techniques in membrane structural biology to identify dynamic hotspots that drive the large conformational transitions in GltPh. We will combine insights from protein crystallography with local variations of thermodynamic stability and protein dynamics measured by hydrogen/deuterium exchange to map the structural components that allow conformational change to occur. In doing so, we will obtain new insights into how GltPh functions, shedding light on the mechanism of biomedically important glutamate transporters. We will use this model system to develop strategies that allow understanding of the molecular basis of substrate transport. The methods developed would be widely applicable to other membrane transport proteins.

Mots clés : glutamate transporter, structure, conformational dynamics, crystallography, thermodynamics, hydrogen, deuterium exchange mass spectrometry

Participants :
- Cornell University (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 246668.4 €
Projet MarHot (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

The amplitude and frequency of extreme events, such as marine heatwaves, are increasing with climate change in the European coasts. The loss of native foundational species (macroalgae and seagrasses) will open windows of opportunity for invasive species, a major threat to Europe's biodiversity that has social and economic impacts. However, our ability to predict the future distribution of marine habitat-forming species under climate change is yet limited. Recently, physiological thermal limits obtained from mesocosm experiments have been combined with species distribution models (SDMs) to produce more consistent predictions in the form of mechanistic or hybrid models. However, mechanistic models remain mostly untested and the existing approaches do not provide an efficient tool to produce multi-species models suitable to identify hotspots of species at risk of extinction and hotspots for invasive macrophytes. MarHot aims at filling this gap by providing an innovative framework to integrate physiological thermal limits into SDMs in order to anticipate future redistributions of marine coastal species. Thanks to an interdisciplinary collaborative research, cutting-edge mesocosms set-ups provided by the hosts and innovative approaches to constrain SDM outputs with experimental evidence, we will investigate multi-species range shifts in response of marine heatwaves. MarHot will take advantage of recent analytical tools to detect extreme thermal events and the increasing availability of global databases on thermal tolerance limits. The project will provide a powerful analytical framework for mechanistic models and open source software for large-scale prediction of coastal macrophyte hotspots under future scenarios of marine heatwaves. MarHot outputs will contribute to achieving the Development Goals and Biodiversity regulations adopted by the EU, placing its researchers at the forefront of biodiversity conservation in the face of climate change.

Mots clés : climate change, mechanistic models, marine macrophytes

Participants :
- King Juan Carlos University (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 172932.48 €
Projet ALGALVANISE (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

The anaerobic digestion (AD) industry is currently facing serious environmental and economic challenges due to the restrictions on the usage of digestate (the slurry residue of the process), coupled with reductions in subsidies for biogas production. It is important for the biogas industry to shift towards an AD biorefinery approach to make valuable co-products from the digestate fraction while recovering nutrients. Algae is an efficient tool for recovering the nutrients due to its ability to assimilate the nutrients efficiently while producing biomass rich in proteins, lipids, carbohydrates, vitamins, and minerals. However, there are no relevant commercially-operating algal digestate treatment plants due to the high energy inputs required for producing and harvesting the algae. ALGALVANISE will advance the state-of-the art by developing two novel concepts: 1) enzyme-assisted enhanced algal cultivation; and 2) combinatorial bioflocculation using bacteria and biopolymers. These two processes are targeted towards efficient nutrient recovery by algae from the digestate and harvesting high-quality algal biomass to produce high-value functional ingredients. The proposed body of research involves extensive training of the hosted researcher in the development of skills that will have a clear positive impact regarding her professional development and career opportunities. It is expected that ALGALVANISE will enable the Researcher to progress significantly with regards to her career goals, a primary one regards being an independent researcher that can develop commercially-relevant high-impact research projects that develop and demonstrate innovations that can ultimately be deployed at flagship facilities. The innovations developed in ALGALVANISE could themselves ultimately lead to a flagship AD-algal biorefinery or they could develop the Researcher’s skills to such a degree that she could lead flagship projects, based on other technologies, in the future.

Mots clés : anaerobic digestion, digestate, biorefinery, algae

Participants :
- Celignis limited (Irlande) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 184590.72 €
Projet RE-GENESis (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The assembly of functional synthetic mammalian genomes is the most ambitious biotechnological challenge of the current century. Synthetic genomics has generated remarkable results in viruses and bacteria, but the de novo assembly of eukaryotic genomes is still limited to a few small chromosomes. Indeed, efficient delivery and genome engineering strategies for systematic genome replacement and assembly in higher eukaryotic cells are still missing. With my project RE-GENESis, I intend to make an essential contribution toward a more comprehensive understanding on the mammalian genome through the synthetic replacement of recoded loci at megabase-scale. My main goal is to demonstrate the feasibility of synthetic genomics and genetic code reprogramming at the megabase-scale in mammalian cells, using mouse embryonic stem cells to identify efficient delivery vectors, genome editing strategies and recoding schemes. I will use CRISPR-Cas in combination with large vectors to find new genome surgery strategies for genome recoding and gene correction and exploit them to replace the 2.4 Mb DMD (Duchenne Muscular Dystrophy)/dystrophin gene as a landmark application. The developed delivery and DNA replacement strategies will be also readily available for genome editing therapeutic approaches in order to correct most of the DMD disease-related mutations in human stem cells. RE-GENESis will thus pave the way for the effective deployment of synthetic genomics in high eukaryotes, expanding our understanding of complex eukaryotic genomes, delivering new tools to modify and regulate mammalian DNA and providing innovative solutions to treat genetic diseases, epidemics and ageing. This highly original and multidisciplinary project combines the strength of CRISPR-Cas with the power of large delivery vectors to yield a project of excellent, innovative science that will exploit my expertise in genome editing while providing me extensive training in genome recoding and synthetic genomics.

Mots clés : syntheic genomics, genome recoding, synthetic genomes, genome editing, genome engineering, stem cells, mesc, crispr cas

Participants :
- UK Research and Innovation (Royaume-Uni) — Coordinator, beneficiary, Recherche, subvention : 224933.76 €
Projet virus-DNP-NMR (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

The atomic-level characterization of large viral particles is one of the greatest challenges of modern structural biology, as well as a fundamental step for the design of effective antiviral treatments. In viruses, the viral genome (double- or single-stranded RNA or DNA) is associated to multiple copies of a capsid protein, forming predominantly icosahedral or helical architectures. These complex superstructures are often studied by X-ray crystallography and electron microscopy (EM). However, only information at low resolution is usually available from EM, and extended and flexible architectures do not provide single crystals amenable to diffraction studies. Over the last years, solid-state NMR (ssNMR) has developed into a powerful structural tool for studying structure and dynamics of solid biological samples at atomic resolution and is now uniquely positioned to complement diffraction-based techniques for the characterization of large functional assemblies. However, proteins of large size or that are available in limited amounts are still inaccessible to site-specific NMR studies. Exploiting a unique equipment available in the host institution, the project aims to remove the current bottlenecks and develop improved dynamic nuclear polarization (DNP)-enhanced ssNMR methodology to push forward the limits of applicability of this technique to macromolecular assemblies, opening new avenues to ssNMR in structural biology. Innovative experimental approaches will be developed to overcome the resolution barriers that currently limit the application of high-field DNP, and new spectroscopic tools will be introduced to allow the structure determination of biomolecules under DNP conditions. The effectiveness and versatility of the newly developed methods will be tested on two viral nucleocapsids of different architectures, the icosahedral capsid of non-tailed bacteriophage AP205 and the filamentous, helical nucleocapsid of Measles virus.

Mots clés : solid state nmr, magic angle spinning, dynamic nuclear polarization, structure, dynamics, protein function, virus capsid

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 185076.0 €
Projet TMSP (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

The behaviour of matter under extreme conditions and the reason why accretion onto many astrophysical objects is accompanied by outflows of plasma like jets, are key questions of astrophysical research. Neutron stars (NSs) are prime laboratories for this investigation. They are the solid-surface bodies in which the most extreme conditions of gravity, density, pressure and magnetization are realized. When they are part of a binary system, and matter is transferred from their companion star, several phenomena occur which have shed light on the physics of mass accretion and NS magnetospheres, as well as the production of high energy radiation and pulsations. An important new class of pulsars spinning at a period of few milliseconds and switching between plasma accretion and ejection was discovered in 2013; they are dubbed transitional millisecond pulsars. These sources alternate between radio and X-ray pulsar regimes as a result of the interaction between the in-flowing plasma and the outward pressure exerted by their magnetosphere and radiation. They experience over few weeks transitions from a rotationally powered regime, in which they behave like radio pulsars, to a regime in which they accrete matter and emit intense high-energy radiation, like standard X-ray binary systems. In between these regimes these NSs display intermediate states which are still to be investigated in detail. Transitional millisecond pulsars provide us with a unique laboratory to study the interaction between the matter inflowing towards the NS, its rotating magnetosphere and the outgoing radiation, particle wind and jets. With this program based on multi-waveband (radio, optical, X-rays, gamma-rays) observations, we will exploit the diagnostic potential of these systems to (i) determine how outflows of plasma are launched and how they are coupled to the accretion process; (ii) measure their mass and spin to constrain their evolutionary state; (iii) study the formation of accretion disks.

Mots clés : neutron stars, pulsars, magnetic fields, mass accretion, outflows, jets

Participants :
- National Institute for Astrophysics (Italie) — Coordinator, beneficiary, Recherche, subvention : 168277.2 €
Projet ALSORES (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : SIGNED

The belowground production of CO2 in soil (soil respiration, SR) represents an important terrestrial carbon source. Being correlated with soil temperature, SR is expected to exacerbate climate change. In addition, SR is expected to change considerably and in a patchy manner especially within the Alpine area, reflecting the effects of altitude, land use and climatic conditions. Previous studies measuring SR along altitudinal gradients, however, struggled with strong differences in environmental influences and with distinct unique faunal and microbial communities among samples. The grand ambition of ACTI-RESP is to provide in-depth knowledge and quantitative information on how microbial and invertebrate communities are influenced by altitude, land use and climate change, and on how microbial activity shapes SR. To quantify the pure effect of altitude and to investigate the effects of climate and land use, I will combine field observations and a manipulative experiment within terraXcube, a facility allowing manipulations of multiple conditions including air pressure to mimic different elevations. Thereby, I aim to further test the advantages of studying intracellular DNA (iDNA) as opposed to the generally studied environmental DNA (eDNA). Being composed by considerable amounts of extracellular DNA, eDNA does not only contain information about intact and active cells (intracellular DNA, iDNA) but also about extracellular DNA from species that might not be recently present. Here, I will study microbial agents actually shaping SR by extracting iDNA, by performing qPCR and 16S rRNA sequencing and by comparing the results to eDNA as well as RNA-based results. In doing so, I aim to - define climate change-related alterations in SR - jointly examine soil invertebrates and microorganisms - firstly describe the pure altitude effect on microbial SR, activity and community patterns - test iDNA quantification as a proxy for microbial activity and SR

Mots clés : intracellular dna, environmental dna, soil respiration

Participants :
- European Academy of Bolzano (Italie) — Coordinator, beneficiary, Recherche, subvention : 183473.28 €
Projet Met4Bone (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

The biomaterials are crucial for the surgical remediation of bone defects caused by various diseases e.g. osteoporosis and traumatic fractures. However, there are several risks associated with this treatment; first, the surgical procedure itself carries a potential risk of inflammation and bone infection, second, the bone replacement can fail requiring revision surgery. In fact, the host immune response to implanted materials and devices is the main factor that will determine a long-term functional outcome of the biomaterial mediated treatment. Therefore, the bone biomaterial ability to modulate the local immune environment for favorable treatment outcomes has to be considered. The usage of bioactive metabolites has emerged as one of the most novel and potent approach for immune response modulation. The incorporation of metabolites with immune regulatory properties seems an especially attractive option for biomaterials as it would ensure site-specific delivery system and allow modulation of the microenvironment. The goal of this project is to develop novel biomaterials with incorporated metabolites as a potentially effective and safe strategy to modulate local immune response towards favorable outcomes of surgical bone remediation. To achieve it, the recent concept of metabolomics with the state of the art biomaterial design and research will be combined in this project. This proposal includes the transfer of knowledge to the host institution and the training of the researcher in new techniques and skills. The multidisciplinary nature of the project is strong, combining materials science, biochemistry, and molecular biology. Results have the potential to pave the way for novel biomaterials significantly improving clinical outcomes for patients suffering from bone injuries.

Mots clés : bioceramics, metabolite, immune response

Participants :
- Riga Technical University (Lettonie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 152202.24 €
Projet HumBrain (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The blood-brain barrier (BBB) is a complex interface that separates the central nervous system (CNS) from the circulatory system and serves to maintain brain homeostasis. There are native P-glycoprotein (P-gp) transporters embedded in the BBB endothelial cell membranes, which play a fundamental role in effluxing out xenobiotics. Such protections come at a steep price, since the BBB is a key roadblock in the delivery of treatments for CNS disorder, including brain tumors and Alzheimer’s, while the P-glycoprotein transporter reduces the effectiveness of chemotherapeutics and is responsible for the development of multidrug resistance (MDR). The HumBrain project will build the first atomistic model of a human P-gp pump embedded in a realistic model of the BBB membrane, and use molecular dynamics simulations in combination with novel free-energy techniques to provide a mechanism for the modulation of the P-gp pump by substrates and inhibitors, in order to address the origins of multidrug resistance and the origins of the high selectivity of the BBB membranes to molecules. This will be complemented by coarse-grained models to address the issue of protein-lipid modulation and alternative ways to turn off the P-gp. The models will be of sufficiently realistic representation to serve as a starting point for translational research to aid in the experimental development of the next generation CNS modulators and targets. The HumBrain project will be carried out by an experienced researcher who worked on membrane proteins during his PhD thesis in the UK and the BBB during his postdoc in the USA in conjunction with an experimental laboratory. The experienced researcher will work with a supervisor in Denmark who has a strong background in modelling complex membranes, including neuronal membranes, as well as membrane proteins, and will benefit from the strong network of simulations present in Denmark, while bringing his expertise from USA and the UK with him.

Mots clés : blood brain barrier, efflux pumps, molecular dynamics simulations, membrane permeability, transport kinetics

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

The boreal forest is one of the most important global carbon sinks but its carbon fluxes and total amount of sequestered carbon depend on the regional climate variability. Because of this sensitivity to climate, boreal trees are also important natural archives of current and past climate change. During this project, we will use a data-model approach to improve our understanding of the links between forests and climate in a Canadian boreal region over the last millennium. More specifically, we will adapt the process-based ecophysiological model MAIDENiso to investigate factors influencing the growth and underlying biogeochemical processes of black spruce (Picea mariana (Mill.) B.S.P.), the most representative species of the North American boreal biome. This will give an insight into carbon storage in the taiga and will provide the first multiproxy (ring widths and δ18O and δ13C in tree-ring cellulose) regional climate reconstruction in Eastern North America over the last millennium. MAIDENiso will be calibrated on a recently developed network of tree-ring data from the taiga of Quebec. This project will have important implications. First, we will get information on the capacity of black spruce forests to adapt to climate change and to act as carbon sink using an innovative approach that can be transferred to study European boreal ecosystems as well. Second, we will reduce the uncertainties on the estimates of the climate variability of the last millennium in a region that has historically been under-represented in the Northern Hemisphere network of climate reconstructions (see IPCC AR5). Finally, we will be able to analyze the impact of each climate forcing (volcanism, solar activity, CO2 concentration) on the regional climate and carbon sink variability. An important aspect of this project is its multidisciplinarity. Climatology, geochemistry, dendrochronology, tree physiology and numerical modelling will be used linking together European and Canadian scientists.

Mots clés : black spruce, boreal zone, carbon storage, climate forcings, dendroclimatology, ecophysiology, forest climate relationship, multiproxy reconstruction, process based model, co2 concentration

Participants :
- Aix-Marseille Université (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 173076.0 €