Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet TSPO METALLODRUGS (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Dr. Leila Tabrizi, an Iranian national, is making an application to this programme to carry out a 24 months project in the area of medicinal chemistry in the group of Dr. A. Erxleben at the National University of Ireland, Galway. The objective of this proposal is the synthesis of novel gold anticancer drugs that simultaneously target two mitochondrial proteins that are associated with cancer progression. Gold(III) complexes will be designed that recognize the translocator protein which is overexpressed in various tumour types and that release the metal upon intracellular reduction to gold(I), a known inhibitor of thioredoxin reductase. Binding of the carrier ligand to the translocator protein and inhibition of thioredoxin reductase will induce cell death pathways in a synergistic manner, thus leading to highly effective and selective anticancer action. Detailed in vitro biological studies will be performed to evaluate the potential of the new anticancer drug candidates, to establish structure-activity relationships and to fully understand their mode of action. The researcher has already an excellent background in coordination chemistry and this project will allow her to deepen and expand her skills in synthetic chemistry, to enter into the biological field by receiving relevant training in cell and biological techniques and to establish important academic and industrial collaborations. The researcher who has recently been awarded a Government of Ireland Postdoctoral Fellowship proposes to carry out further research training at NUI Galway which is strategically developing strength in Biomedical Research and Cancer, one of the most important and challenging branches of Chemistry/Biochemistry in Europe. NUI Galway will also provide training in transferable skills and mentoring to the researcher. Both the scientific and personal training will contribute to her personal development and will allow her to reach professional maturity as an independent researcher.

Mots clés : gold, anticancer, target delivery, antimitochondrial

Participants :
- National University of Ireland (Irlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 175866.0 €
Projet NANOZID (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Dr. Sybil Obuobi was awarded her PhD in Pharmacy at the National University of Singapore (Singapore) in July 2018 and is very excited to pursue a postdoctoral fellowship at the University of Tromso The Arctic University of Norway (UiT, Norway) under the supervision of Prof. Natasa Skalko-Basnet, a renowned expert in advanced drug delivery. Their project will exploit DNA nanohydrogels, as a novel universal platform to improve the loading efficiency of antimicrobials in mannosylated liposomes against intracellular and topical biofilm infections. This approach fills the current research gap for high drug loading innovative systems in nanomedicine and holds great promise to improve drug efficacy against difficult-to-reach pathogens thus, there is immense potential for new patentable technologies/products. This area of research will advance knowledge in antimicrobial drug delivery and the outcomes will appeal to formulation scientists, R&D scientists and people with persistent skin infections that impose significant economic challenge and contribute to the spread of antimicrobial resistance. With access to state-of-the-art equipment and interdisciplinary environment within the participating organisations (UiT, University of Helsinki and BIOTEC Pharmacon ASA) and administrative support, Dr. Obuobi will acquire new skills in life sciences, expertise in state-of the art biofilm models, hands-on teaching experience, transferrable skills in grant/patent applications and project management alongside new knowledge in product development. Against the backdrop of her notable achievements as a young scientist, she has the capacity to attain research growth through this fellowship and will seize this opportunity to diversify her competency, improve her record of publications, gain independence, build new international networks and apply for an ERC-StG grant- outputs that are expected benchmarks for academic appointments and essential to launch her career within Norway/Scandinavia.

Mots clés : liposomes, dna nanogels, antimicrobials, mannose, bacteria infections

Participants :
- UiT The Arctic University of Norway (Norvège) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 214158.72 €
Projet ScalePlantProt (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

Drawing on the expertise from the Experienced Researcher, this MSCA application aims to significantly advance the understanding of phase behaviour in plant proteins, to enable development of two primary products for sustainable plastic replacement, microcapsules and thermoplastic flexible films. Currently, large-scale production of plant protein based plastic alternatives is hampered by a lack of advanced knowledge of the phase behaviour of plant proteins. This research programme thus aims to for the first time systematically investigate the key phase transition of plant proteins — thermal phase transition and phase separation. This objective will be achieved by uniting two sets of skills: i) the Experienced Researcher’s expertise in plant protein self-assembly and ii) specialized knowledge of chemists, engineers and business management at Xampla Ltd for the commercially successful application of plant protein materials. The breakthrough aspect will be uniting traditional polymer science regarding phase transition and molecular understanding of proteins – the obtained materials can be manufactured using established industrial platform used for polymer processing. The approach thus makes the products competitive with current bio-based polymeric materials in market, or even synthetic plastic materials. Therefore, the research program will boost the European green-material market and addresses the Horizon 2020 societal and economic challenges.

Mots clés : plant proteins, thermoplastic processing, phase separation, self assembled materials, scalable processing

Participants :
- Xampla ltd (Royaume-Uni) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 212933.76 €
Projet NanoSpace (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Driven by their large variety of potential applications, their nanometre-scale dimensions, and their appealing high aspect ratio, scientists are increasingly being attracted to the challenge of designing artificial nanotubular and nanoporous materials. In this context, NanoSpace arises as an unconventional and versatile project, based on molecular self-assembly, towards organic water-soluble tubular architectures endowed with well-defined hydrophobic nanospaces. The MSC candidate, Dr. Fátima Aparicio Hernández, will focus on introducing catalytic function to such porous nanostructures. The inner confined space of the nanotubes will be provided with controlled chemical coatings (i.e. hydrophobic) so that they can extract and host molecules as a function of their size and chemical affinity. The attachement of catalysts allows the transformation of specifically recognized molecules. The ultimate objective would be the fabrication of advanced nanoporous materials for the extraction and catalytic transformation of specific molecules as a function of their size and chemical nature. NanoSpace introduces fundamental challenges and unprecedented approaches in chemical self-assembly and constitutes the best research scenario for the candidate to learn from different fields across physical and biological sciences and to further develop her scientific career. The host Nanostructured Molecular Systems and Materials group, directed by Prof. David González-Rodríguez (DGR), is an active, emergent group, with a strong background in the topics of the proposal, and funded, among others, by an ERC-granted project. The host institution, the Universidad Autónoma de Madrid (UAM) is one of the most relevant and dynamic universities.

Mots clés : self assembled functional systems, artificial nanotubes, nanotube network, nanochannels, noncovalent systems, amphiphilic systems, molecular recognition, catalysis, dye recognition

Participants :
- Autonomous University of Madrid (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 170121.6 €
Projet ChlorPlant (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : SIGNED

Drought greatly reduces crop productivity and global food security, and is becoming more frequent and severe under climate change. Excessive nitrate fertilization is the main source of water pollution, and due to the enormous energy and carbon cost of industrial fertilizer production, is a major cause of global warming. Therefore, it is critical to understand how to optimize the use of water and nitrogen for plant production and crop yield. Chloride (Cl−), although traditionally considered a toxic ion for agriculture, has emerged as a beneficial macronutrient for plant growth due to its roles in water relations and photosynthesis, recently discovered by the host group. The current project proposes a unique integration of approaches (from molecular to ecophysiological) in tomato, a model crop of great economic value, with the aim to enhance fundamental knowledge of how Cl− modulates the effects of water management on plant development, photosynthesis, turgor maintenance, yield and drought resistance. Our major objectives are to provide new knowledge on i) the role of Cl− homeostasis on plant development, and ii) its relevance on plant improvement of water- and nitrogen-use efficiency, and iii) transfer this knowledge to the practical management of a crop. These objectives will integrate state-of-the-art process-based models of photosynthesis and stomatal conductance into a mechanistic whole-plant model that includes frontline phenotyping. This novel and multidisciplinary project will be carried out by an applicant with strong scientific expertise in plant molecular physiology and agriculture, who perfectly matches the proposed project, and it will be implemented in a laboratory with an internationally recognized excellence in the study of crop water stress and precision agriculture. This combination provides a unique scientific platform for the research training of the applicant and the development of frontline research in Plant Sciences and Agriculture.

Mots clés : abscisic acid, chloride, crop yield, drought, fruit quality, mesophyll diffusion to co2, nitrate, photosynthesis, plant development, stomatal conductance, tomato, water relations

Participants :
- Spanish National Research Council (Espagne) — Coordinator, beneficiary, Recherche, subvention : 259398.72 €
Projet MOOAC (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Drug development is stuck in an innovation gap, in which it incurs staggering expenses and takes many, ten to fifteen, years to get a drug to market, furthermore, during the process many animals are sacrificed in preclinical work, and in the end many times the results from the animal studies does not accurately predict what will happen in humans, resulting in failures, delays, and recalled drugs. There is currently a gap in the preclinical testing platform for therapeutics. Organ-on-a-chip technologies of closing this gap, and have the potential of curtailing the high experimental costs and complexities associated with in vivo studies, and eventually evolving into next generation tools for therapeutic validation and development. We propose that by using a multi-compartment microfluidic platform, while integrating synthetic biointeractive hydrogels into and between the compartments, we will be able to produce a multi-organ-on-a-chip which recapitulates organ-like functions in each compartment and a vascular-similar conduit system between compartments to produce an early stage human on-a-chip for future therapeutic assessment and development applications. This project aims to develop a preliminary human-on-a-chip device, initially focusing on a heart-, and liver-on-a-chip and an endothelialized-conduit system between and through the two organ compartments. Successful production of this platform will improve the therapeutic and pharmaceutical development pipeline, while also minimizing our reliance on animal testing in accordance with the needs and guidelines within the EU. The long term implications of this work would result in increasing the throughput of therapeutics, directly minimizing the cost of drug development and increasing the efficiency. This would lead to lowered economic burden to produce drugs, as well as quicker turn around, having large implications on improving the quality of life in globally.

Mots clés : microfluidics, organ on a chip, biomaterials, in vitro models, pharmaceutical testing

Participants :
- Elvesys (France) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 185076.0 €
Projet Target5LO (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Drug efficacy is cornerstone for successful drug discovery programs. Considering that, on average, FDA-approved drugs modulate dozens of off-targets it remains imperative to find strategies to overcome adverse drug reactions correlated with pernicious polypharmacology. In fact, several chemical entities displaying promising anticancer are discontinued from drug development pipelines due to narrow therapeutic windows in pre-clinical models. Here, we propose the development of antibody-drug conjugates exploring the unique bioactivity profile of the naphthoquinone natural product-lapachone (Lp) against acute myeloid leukemia (AML), an unmet medical need. Using a machine learning method, we disclosed Lp as an allosteric modulator of 5-lipoxygenase (5-LO), correlated its anticancer activity with 5-LO expression in blood cancers and showed its efficacy in a disseminated mouse model of AML. In this project, a comprehensive investigation of novel means for the targeted delivery of Lp to leukaemia cells is sought after, considering both the promising bioactivity profile but also the significant toxicity in untargeted dosage forms. We apply state-of-the-art synthetic medicinal chemistry to design and access cleavable linkers, and site-specifically conjugate Lp to an anti-IL7R antibody, a validated biomarker in AML and other leukaemia’s. We aim at employing biophysical and chemical biology approaches to validate quantitative and fast release of Lp with accurate spatiotemporal control in in vitro disease models. Finally, we will validate the deployment of the constructs through preclinical in vivo models of AML. We foresee broad applicability of the developed technology, which may have profound implications in drug discovery. Upon successful completion of this research program, we hope to yield a new targeted drug to treat AML patients with improved efficacy and reduced side-effects.

Mots clés : antibody drug conjugates, 5 lipoxygenase, lapachone, acute myeloid leukemia, bioconjugation

Participants :
- University of Cambridge (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet MYFUN (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Dryland ecosystems are a key terrestrial biome, covering 45% of the Earth´s surface and supporting over 38% of the total global population, but their functioning and the goods and services they provide are vulnerable to global environmental changes such as increasing land use intensity (e.g. grazing pressure) and climate aridification. Mycorrhizal fungi, i.e. obligate plant symbionts colonizing the roots of 90% of all land plants, contribute substantially to dryland biodiversity, to their functioning, and the provision of goods and services by dryland ecosystems. In exchange for plant assimilated carbon, mycorrhizal fungi increase plant nutrient supply, influence soil formation and aggregation, plant defence to herbivory and resistance to drought, among other important processes. Through these mechanisms, they influence plant diversity, multiple ecosystem functions, such as nutrient cycling or biomass production, and likely modulate ecosystem responses to aridity and grazing pressure, which are forecasted to increase in drylands under global environmental change. Mycorrhizal effects depend on environmental conditions and species traits determining the efficiency of the resource exchange between plants and fungi. However, to date little is known about the contribution of mycorrhizal fungi to the diversity and functioning of drylands or to the capacity of drylands to provide multiple functions simultaneously (i.e. multifunctionality). We also do not know how the contribution of mycorrhizal fungi to dryland multifunctionality might change under forecasted global environmental change or depending on the resource economy of the plant community. The MYFUN project aims to fill these gaps in knowledge by assessing the contribution of mycorrhizal fungi to dryland multifunctionality in response to environmental stress (increased aridity, grazing pressure) and plant resource economy.

Mots clés : drylands, mycorrhizal fungi, ecosystem functioning, plant functional traits, plant root traits, plant aboveground traits, plant soil interactions, climate change, land use change, aridity, grazing

Participants :
- University of Alicante (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 160932.48 €
Projet DYS_FUNCTION (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Duchenne muscular dystrophy (DMD) stems from loss of dystrophin in skeletal and cardiac muscles, which leads to loss of ambulation and cardio-respiratory failure. The most promising treatment that could be applicable to 83% of DMD patients is exon skipping, a technology where the EU is a world leader. Antisense oligonucleotide mediated exon skipping targets DMD pre-mRNA to induce skipping of specific exons and restore the open reading frame. This allows expression of shorter dystrophin proteins that lack domains encoded by the skipped exon(s). A crucial question is how to predict which short dystrophins will be stable and functional. This knowledge is fundamental to select DMD patients that would most benefit from this treatment and identify exons worth targeting via exon skipping. The goal of this proposal is to develop a new use of exon skipping technology to rapidly generate mouse models to screen short dystrophins for in vivo stability and functionality in both skeletal and cardiac muscles. This is made possible by a new exon skipping chemistry developed in the UK with unparalleled skipping efficiency in vivo and capable of targeting the heart. I will use this technology to create mouse models for two short dystrophins generated in DMD patients undergoing exon 51 skipping in the current UK clinical trial. I will then biochemically assess their stability and functionality in limb, cardiac and respiratory muscles. Parallel histological studies will assess the presence of muscle pathology with a focus on heart and diaphragm that cannot be sampled in DMD patients. This project will serve as a trampoline for future studies to identify dystrophin exons that when skipped will produce functional proteins with clinical benefits. In addition, this research will generate new fundamental knowledge on dystrophin domains critical for muscle function and may help in the prognosis of DMD patients currently undergoing exon 51 skipping.

Mots clés : exon skipping, muscular dystrophy

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

Due to anthropogenic climate change, the Arctic Ocean (AO) is warming rapidly and sea ice is retreating dramatically with a loss of ~40% since 1980. Sea ice retreat will have complex effects on nutrient availability and, subsequently, primary productivity with implications for atmospheric CO2 sequestration through sedimentary organic carbon burial. Nutrient cycling in the AO is poorly constrained in the modern and even less is known about how nutrient delivery will evolve as sea ice continues to retreat. For the proposed project (PaNDA), I would move from the United States of America to Newcastle University in the United Kingdom to undertake a project designed to improve our understanding of how nutrient dynamics in the Eurasian Basin of the AO evolve under warmer climate conditions, which is extremely timely given the rapid warming occurring in the AO due to modern climate change. PaNDA is in line with the research priorities identified in Horizon 2020, as it focuses on both climate change and the Arctic region. PaNDA aims to reconstruct nutrient cycling over the last ~150 ka from sediment samples and pore waters collected north of Svalbard during the 2015 TRANSSIZ expedition (“Transitions in the Arctic Seasonal Sea Ice Zone”), focusing on two previously identified warm periods of sea ice minima, the Early Holocene (11-13 ka) and Marine Isotope Stage 5e (116-129 ka). Nutrient records will focus on changes in the cycling of major bioessential nutrients (phosphorus, nitrogen, and silica) and the main biolimiting micronutrient (iron) reconstructed using bulk elemental concentrations, sequential extractions, and isotope geochemistry. My background in Quaternary paleoceanography and carbon and nitrogen cycling will complement the Arctic experience and inorganic biogeochemical expertise at Newcastle University and the University of Oldenburg, enabling us to reconstruct bioessential nutrient (N, P, Si, Fe) behaviour during previous sea ice minima.

Mots clés : phosphorus, iron, silica, nitrogen, biogeochemical cycling, sea ice, paleoceanography

Participants :
- University of Leeds (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €