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

The development of gold nanostructures is a topic of high interest due to their extensive use in biomedical applications, biosensing and bioimaging because of their specific properties: high stability, ease of detection, facile synthesis and functionalization, etc. It would be of potential interest to predict the photobehaviour of AuNPs before introducing them in a biological environment. In this respect, when NPs interact in a living milieu, proteins will adsorb onto its surface generating a protein corona; this may provoke changes in the biological function of the protein and in the photophysical properties of the AuNP; thus, the photophysical behaviour of AuNPs in solution cannot be directly extrapolated to the biological media. These effects have been barely investigated up to now. The design of new gold nanoparticles whose photophysical behaviour can be extrapolated in a greater degree to a biological environment is of potential interest for in vivo applications due to the fact that their photobehaviour would be predictable within cells. Functionalization of AuNPs with nonsteroidal anti-inflammatory 2-arylpropionic drugs is proposed. These drugs are widely prescribed and are able to generate cytotoxic singlet oxygen, which induces cell tumour death. Their photophysical properties have been well characterised in solution. However, to the best of our knowledge, functionalization of AuNPs with drugs of this family has never been performed. The photophysical properties of the new nanomaterials will be studied in different microenvironments that tend to mimic cellular milieus, such as micellar or microemulsion media. Investigation of their photobehaviour in the presence of proteins is also planned. Finally, studies in an intracellular environment and in vivo will also be performed in order to check the potential application of the new conjugates as biosensors or photodynamic therapy agents.

Mots clés : nanoparticles, fluorescence, laser flash photolysis, biosensors, intracellular analysis, photodynamic therapy

Participants :
- University of East Anglia (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet COPQE (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

The development of integrated circuit technologies at scales approaching the quantum regime sparked an immense interest in the field of quantum information processing (QIP). These advances changed our understanding of the relation between information and quantum physics, and triggered a vast research effort into quantum engineering, which seeks to meet the practical challenges of controlling quantum systems with extremely high fidelities by encompassing both fundamental physics and engineering. With this proposal we intend to enable the systematic incorporation of composite pulses into practical quantum engineering. We will address the outstanding challenges of unwanted interactions with the environment and time-varying noise in the control fields, which lead to reduction in the fidelities of the operations. The proposal is aimed at the following research objectives: 1. Develop composite pulses for quantum engineering with qubits that are robust to decoherence and non-static control errors, 2. Create the control toolbox of robust quantum engineering with multi-dimensional quantum systems, 3. Transfer robust CPs protocols for quantum engineering to polarization physics and waveguide arrays. The proposed research will be of considerable theoretical and experimental value, as it applies to any physical system with the ability to perform single- and two-particle gates, including trapped ions and atoms, Nitrogen-Vacancy centers in diamond and others. It will also have an impact on a wide range of fields beyond QIP, such as control theory, optics, and precision metrology. The researcher and the host group at Sofia University will combine their complementary expertise to achieve these objectives. The applicant will receive significant training in transferable skills, and expand her knowledge in theoretical methods. Additionally, a secondment at Weizmann will allow the applicant to develop experimental expertise and contribute profoundly to her career.

Mots clés : quantum control, composite pulses, quantum engineering

Participants :
- Bulgarian Academy of Sciences (Bulgarie) — Coordinator, beneficiary, Recherche, subvention : 140994.0 €
Projet KEME (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

The development of knitting was a key technological innovation for which there is little published scientific evidence. There are more than 100 knitted caps from the early modern era in museum collections worldwide - an astonishing number given the paucity of extant garments from the period. Despite their diverse locations, they have remarkable similarities in their materials and manufacture which illustrate trade in knitted caps as consumer goods in the emerging early modern European marketplace, demonstrate how knitting created new fashions for men indicative of rank and status, and facilitate theory on the cultural significance of the hat as an essential male accessory. My preliminary study of the caps tracks clear patterns in the data: five typologies are identifiable and when contextualised with pictorial and documentary sources, their cultural significance as functional and fashionable men’s wear is clear. I believe the caps’ potential as indicators of the development and growth of knitting technology is valuable yet vulnerable. The caps are fragile and deteriorating, a process accelerated by each viewing, for which there is pressing and unsatisfied demand. I propose immediate rigorous scientific study (radiocarbon dating, microscopic examination, x-radiography, fibre and dye identification, and degradation analysis) and interdisciplinary research into contemporary sources to chart an economic map of early knitting, to define terminology for further scholarly work, and to develop theory about men’s headwear in the 16th century. An online database will make the data accessible to scholars, museum pedagogues and craftspeople, who demand access to the caps. Journal articles, practical workshops and social media will disseminate my conclusions and my development of theory. I will give voice to an eloquent body of evidence about early modern knitting technology, which threatens to be silenced forever if scientific analysis is delayed.

Mots clés : archaeology, pedagogy

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212194.8 €
Projet PROFOLIG (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

The development of ligands that selectively bind to a given protein surface is a challenging area of research with potential applications in diagnostics, pharmacology or therapy. Current approaches include small molecule screening, the design of medium sized epitope mimetics (e.g. alpha helix mimetics) and directed evolution methodologies (e.g. ribosome display). In this project, we intend to initiate an essentially unexplored approach: the design from first principles of synthetic ligands derived from helical aromatic oligoamide foldamer backbones bearing proteinogenic side chains to target the surface of a given protein: interleukin 4 (IL4). Helical aromatic amides appear to be well suited for this purpose thanks to their predictable, tunable and stable conformations in solution; their relatively easy synthesis of secondary and tertiary-like structures as large as small proteins; and their high amenability to crystal growth and structural elucidation. Specifically, we intend to explore molecular recognition rules between large (2-15 kDa) aromatic oligoamide foldamers and a target protein surface, and to validate a novel iterative method based on combining covalent attachment and structural characterization. The proposed strategy thus consists in structure-based iterative design. The following steps will be implemented: 1) synthesis of a small pool of foldamer sequences; 2) covalent attachment of each of them via a disulfide bridge to the surface of a recombinantly expressed IL4 cystein mutant, and screening for foldamer-protein interactions through foldamer helix handedness induction by the chiral protein surface; 3) structural characterization of the interactions, mainly by crystallography, within selected protein-foldamer adducts; 4) design of new and improved foldamers. Ultimately optimized interactions should produce foldamers that bind to IL4 without the assistance of the covalent tether.

Mots clés : foldamers, molecular recognition, proteins

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 185076.0 €
Projet distalC-Hfun (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

The development of methods for the transition metal (TM) catalyzed functionalisation of C–H bonds has emerged as an extremely important topic in present-day organic synthesis aiming at providing tools that allow treating the ubiquitous and normally inert C–H bonds as any other functional group for synthetic modifications. However, controlling the site of C–H activation or distinguishing between the subtle differences in reactivity of two given C–H bonds is one of the major challenges yet to be addressed. In this context, meticulous design of directing groups (DG) over the last decades has enabled a variety of relatively unreactive C–H bonds to be functionalised under transition metal catalysis. To date, much progress has been made in developing strategies for the ortho-functionalisation of arenes mainly through the installation of DGs in the stoichiometric amount. However, these DGs are not part of the final target molecule; as a consequence, its covalent installation and/or removal from the substrate will add additional steps to the synthetic sequence thus lowering the efficiency and applicability of these approaches. On the other hand, distal meta- and para-C–H functionalisation approaches, are extremely scarce despite these substitutions are widespread motifs amongst biologically active molecules. The research outlined in this proposal aims at developing a process that makes use of a transient DG in a catalytic amount which binds reversibly with carbonyl compounds via imine formation leading to a novel direct meta- and para-functionalisation methodology. Precisely, we seek to develop a protocol that removes the need for the use of stoichiometric directing groups to activate distal C–H bonds. The realization of the proposed objectives will push the boundaries of the state-of-the-art in the area of remote C–H bond functionalisation by providing atom and step economical access to molecules that are difficult to prepare via conventional multi-step routes.

Mots clés : transient directing group, c h bond activation, meta c h, para c h, transition metal, catalyst, ligand, metallacycle, palladium, aminoquinoline, imine, enamine

Participants :
- University of Manchester (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €
Projet Gal3-BrainMets (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The development of new cancer treatments has significantly improved life expectancy of patients. However, these advances increase the risk of suffering from secondary tumours (metastases). Particularly, breast cancer brain metastases are a major cause of morbidity, with meagre life expectancy (3-18 months). These facts highlight the urgent need to find better treatment against this disease. Immunotherapy has recently gained great momentum in the clinic to treat different type of cancers. However, its therapeutic use for metastatic spread to the central nervous system (CNS) remains scarce. The immune response within the CNS during metastasis progression greatly depends on microglial cells (resident CNS macrophages). Their roles in neuroinflammatory and neurodegenerative processes have been intensely investigated, whereas their function in metastasis has received minor attention. During brain metastasis, microglia show impaired immune defence, secreting a variety of anti-inflammatory cytokines (e.g. IL-10 and TGF-B) and growth factors which may contribute to metastasis progression. A key molecule which might alter such adverse behaviour is beta-galactoside-specific animal lectin galectin-3 (Gal-3). Studies of this promiscuous protein has shown a pivotal role during tumour progression and metastasis to non-CNS sites. Importantly, recent studies from Prof Venero’s group have shown how inhibition of microglial Gal-3 shifted the phenotype of these cells into a more pro-inflammatory state. Therefore, since pro-inflammatory state in microglial cells has been described to exert anti-metastatic effects, Gal-3 inhibition may provide a powerful and novel brain metastasis immunotherapeutic approach. Moreover, the fact of the existence of Gal-3 drugs in current clinical trials enhance the possibility of using this strategy as neo-adjuvant therapy to treat breast cancer patients at risk of brain metastasis.

Mots clés : brain metastasis, microglia, galectin 3, breast cancer, immunotherapy, macrophages, in vivo, mouse

Participants :
- Universidad de Sevilla (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 170121.6 €
Projet BiMetArylation (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

The development of new methodologies for the preparation of biologically and industrially interesting compounds remains one of the fundamental challenges in chemistry. Aryl-aryl bond formation is one of the most important tools in modern organic synthesis. These biaryl motifs are very often found in pharmaceutical, agrochemicals, organic materials and natural products. Given the abundance of C–H bonds in organic molecules, the selective activation and use of these bonds in controlled synthetically useful transformations is an immensely important topic. In this context, direct C–H arylation has emerged as a powerful methodology for the synthesis of biaryls. However, in most methodologies described so far, the arene substrate must fulfil certain requirements such as containing strong electron-withdrawing or electron-donating groups, or bearing special directing groups. Substrates lacking this feature either are unreactive or must be used in large excess (often as solvents). The coupling of ‘simple arenes’, which are not considered as pi-electron-deficient or -rich remains challenging. The research outlined in this proposal aims at developing a new bimetallic catalytic methodology able to couple equimolecular amounts of ‘simple arenes’ under mild conditions. To do so, we envision a strategy involving a bimetallic double catalytic system. The pi-coordination of the non-activated arene to a metal fragment facilitates the C-H arylation catalysed by palladium complexes which followed by a ligand exchange gives the desired biaryl product, regenerating the initial arene catalyst. The realisation of the objectives of this project would result in a powerful tool for the synthesis of biaryls, coming from simple arenes, improving atom economy, efficiency and sustainability of the reactions, while reducing waste production.

Mots clés : c h activation, biaryls, bimetallic catalysis

Participants :
- University of Manchester (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet OWLi (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

The development of new technologies changes the ways we use language, constantly switching from oral to written language, when we text, talk on the phone, or write an email, making it timely to study language modalities and their interactions. Speaking and writing differ at least on the motor actions they require. Nonetheless, the cognitive processes leading to word selection are likely to be similar. Establishing precisely the specificities of speaking and writing in terms of cognitive, linguistic and motor processes, as well as neural pathways, remains to be accomplished. The aim of this project is to identify the commonalities and differences between language modalities, by looking at collaborative and competitive processes at play between modalities. This project takes advantage of a combination of cutting-edge behavioural, electrophysiological and neuroimaging techniques to tackle the questions at hand. First, I will evaluate the interaction between language modalities when learning the oral and written forms of novel words. Specific processes are in place during language acquisition, making it important to examine learning contexts separately. The originality of this study resides in investigating response execution mechanisms (e.g., spoken durations), and not only response initiation (e.g., reaction times). Second, I will evaluate the structural and dynamic interplay between language modalities at the neural level, combining electrophysiology and neuroimaging. By examining speaking and writing within the same experiments, this study aims to provide a more complete picture of language processing. This action will constitute an important body of knowledge relative to the modalities of language production, both during and after learning. Speaking and writing are crucial parts of our daily life and elucidating mechanisms underlying their interaction has direct implications for language education, as well as for developmental disorders (e.g., dyslexia).

Mots clés : language production, typing, word learning, neuroimaging

Participants :
- Basque Center on Cognition, Brain and Language (Espagne) — Coordinator, beneficiary, Recherche, subvention : 160932.48 €
Projet ThermalDFT (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

The development of sustainable energy sources poses a great challenge for our society. Due to the scarcity of natural resources it is of crucial importance to optimize the efficiency of our energy production. Virtually every energy generation process is accompanied with the generation of waste heat, for example in the form of plumes from power plants. Even if only part of this waste heat is transformed into useful energy the overall efficiency of energy production is increased. In recent years there has been renewed interest in thermoelectric phenomena, due to their potential impact on designing new devices capable of converting waste heat into electricity. Furthermore, it has become evident that nanoscale devices, which implement their functionality at the level of single molecules, potentially offer a much enhanced efficiency for the conversion of heat to electricity compared to bulk materials. This project aims at providing the necessary tools to describe the efficiency of nanoscale thermoelectric devices based on their microscopic structure. To this end a density-functional theory (DFT), dubbed thermal DFT, is developed. The innovation of thermal DFT is to address charge and energy (or heat) degree of freedoms on the same footing, which is crucial for addressing thermoelectric phenomena. It will allow to predict the thermoelectric properties of molecular devices by numerical simulations. This can dramatically reduce the money and time spent in the experimental search for highly efficient thermoelectric devices by selecting materials with promising thermoelectric transport coefficients. Within this project the approximations required for a numerical implementation of the theoretical thermal DFT framework are derived. In addition, thermal DFT will be numerically implemented and benchmarked against available experimental data on the thermoelectric transport coefficients of molecular junctions.

Mots clés : thermoelectric phenomena, density functional theory

Participants :
- Max Planck Society (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 159460.8 €
Projet MetalloGutRepair (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The digestive tract has been assigned important but complex tasks. It provides our body with nutrients and water. It gets rid of pathogens while allowing the commensal flora to thrive, and it quickly repairs injuries caused by the constant mechanical and biological stress. Lgr5+ intestinal stem cells (ISCs) play a crucial role in these processes, but when ISCs are lost due to injury, differentiating cells must ‘de-differentiate’ into ISCs to regain the stem cell pool. The cellular signalling processes that control these repair processes are still largely unknown. Matrix metalloproteinases (MMPs) are enzymes capable of cleaving both matrix and non-matrix proteins. My preliminary data identifies Mmp17 as a crucial regulator of inflammation-induced intestinal regeneration. Notably, Mmp17 is only expressed in a subpopulation of visceral smooth muscle cells, and thus is absent from the epithelium. I hypothesize that Mmp17+ cells provide essential niche factors for repair. In addition, I propose that Mmp17 plays an important role in tumorigenesis. First, I will test the role of Mmp17 in intestinal regeneration after whole-body irradiation. My in vivo studies will be supported by an original ex vivo co-culture model, where I combine organoids and muscle cells. Next, I will test the role of Mmp17 in an established tumorigenesis model. Finally, I will attempt to identify the responsible substrate that mediates these processes, both by unbiased mass spectrometry experiments, and by focusing on likely candidates. This work will reveal a new role for muscle cells in the repair of the intestinal epithelium, and may have important implications for treating inflammation, infections and gastrointestinal cancers. MetalloGutRepair thus combines my expertise in smooth muscle cells with that of the host lab in intestinal disease models, in a research environment where I will reach my immediate goals while developing crucial skills for my long-term career as an independent researcher.

Mots clés : regeneration, matrix metalloproteinases, inflammation, intestinal smooth muscle, autocrine signaling, stem cell niche

Participants :
- Norwegian University of Science and Technology (Norvège) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 196400.4 €