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

The overall research objective of this project is to develop novel photoswitchable kinase inhibitors (PKIs), targeting on REarrange during Transfection (RET) for use in living cells and in zebrafish (Danio rerio). Controlling the action of kinases in a reversible way will have an exceptional potential for investigating signal transduction in zebrafish. In this work, photoswitchable RET kinase inhibitors based on azo-functionalized pyrazolopyrimidines will be developed, enabling photonic control of RET activity with substantial differences in inhibitory activity between the two photoisomeric forms. Such RET inhibitors are currently not available. RET is expressed by the immune cells of the brain, the microglia and is mediating activation of the cells. Microglia has been shown to be responsible for both protecting and harmful effects in neurodegenerative disorders. Although RET has been shown to be involved in neurodegeneration, its role in Alzheimer’s disease (AD), where microglia play an important role, is not known. The ability to manipulate the activity of RET using light would result in temporal control of enzymatic activity, thus serving as a valuable molecular tool to study the function of RET in microglia cells and further our understanding of AD. The research project is (1) highly interdisciplinary, (2) timely due to the recent interest of photopharmacology and (3) innovative by combining zebrafish imaging with photopharmacology to study signalling relevant for development of AD. This fellowship will ensure the best possible career opportunities for me as I will receive substantial training in cutting-edge approaches, gain mentor and supervision skills, presentation skills and critical assessment skills, largely expand my collaborative network, and gain the fundaments for becoming a mature, independent researcher within the field of chemical biology.

Mots clés : rearrange during transfection  ret, photoswitchable kinase inhibitors, photoisomerisation, zebrafish, alzheimer s disease  ad

Participants :
- University of Gothenburg (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 185857.2 €
Projet PATTENZYME (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

The pharmaceutical industry is a major industrial sector in the EU (annual sales of €130 billion). In contrast to other manufacturing sectors, the sector faces a significant challenge in its reliance on batch processes, with synthesis of active pharmaceutical ingredients (API) occurring via individual reaction steps. Such an approach is not well suited to modern manufacturing methods, and reflects a gap in the state of the art in the manufacture of APIs, where flexible plug and play modular systems to manufacture the drug product from raw materials when they are needed reactors are required. PATTENZYME will address this gap by using electrochemical approaches for the targeted and selective immobilization of bio/catalysts in modular 3D printed bio/reactors. The project will utilise a multi-disciplinary approach that combine electrode preparation and characterisation, modelling of fluid flow and rates of reaction, enzyme immobilisation and characterisation with the preparation and characterisation of 3D printed flow reactors. Specifically, PATTENZYME will immobilize laccase on high surface area supports in 3D-printed reactors for the production and controlled delivery of H2O2 to spatially patterned bio/catalysts for enantio/regio selective oxidation reactions with the goal of developing a bio/reactor for the enantioselective oxidation of omeprazol sulphide to esomeprazole. The bio/catalysts will be immobilised on nanoporous gold electrodes at specific locations in the channels of the bio/reactor. Detailed modelling and characterisation studies will be performed to ascertain the optimal location of the catalysts, the architecture of the channels and the flow rate. 3D printed prototype reactors will be produced and characterised to prepare the optimal system for the oxidation of omeprazol sulphide. PATTENZYME will provide advanced training in a multidisciplinary training programme that is informed by leading expertise in the pharmaceutical sector.

Mots clés : electrochemical bio, reactor, enzyme immobilisation, laccase, unspecific peroxidases, nanoporous gold  npg, kinetic modelling, 3d printing, flow reactors

Participants :
- University of Limerick (Irlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 184590.72 €
Projet BCPPlus (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

The pharmaceutical industry is increasingly seeking new tactics for the structural modification of drug candidates to avoid metabolic susceptibility, or to improve pharmacokinetic properties. Analogues called 'bioisosteres', which mimic the dimensions and substituent directionality of problematic structural motifs, but which are not themselves subject to the same pharmacological issues, offer one solution. Often based on scaffolds not found in ‘typical’ drug candidates, bioisosteres can additionally occupy new areas of intellectual property space. Within this growing field, rigid polycycles such as bicyclo[1.1.1]pentane (BCP) are receiving significant attention as arene bioisosteres, as they exhibit similar ring diameters and substituent positioning, and also improve many pharmacokinetic properties relative to the parent arene. Despite the attractive nature of these motifs and current interest, the lack of general routes to complex BCP ring systems means this template is not yet fully accessible to industry. The invention of mild methods for [1.1.1.0]tricyclopentane (TCP) ring opening and functionalization could revolutionize use of BCPs in the pharmaceutical sector. One method not explored to date is an atom transfer radical addition reaction (ATRA) strategy. Using aryl or alkyl halides, ATRA could deliver an abundance of previously inaccessible polysubstituted BCPs from generalized TCP, which would revolutionize this immature, cutting-edge area of organic and medicinal chemistry. This research proposal seeks to: i) explore general and mild ATRA-based syntheses of BCP derivatives, including ring-expanded (hetero)bioisosteres; ii) functionalize BCP products using a range of contemporary processes, including C–H or C–X activation; and iii) apply these methodologies to synthesize BCP drugs / natural product analogues, and to test their biological activity via an industrial collaboration.

Mots clés : bicyclopentanes, bioisostere, atra, radical chemistry, c h activation, photoredox, iron catalysed cross coupling, artificial amino acid, peptide drugs

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

The phases of matter are determined by competing interactions. For example, in our everyday experience, a fluid will be gas or liquid depending on the interplay of attractive interatomic interactions and short-range repulsion. In the case of dilute quantum fluids, the interatomic distances are much larger than the range of the interactions that bind conventional liquids; thus, this phase transition is normally not possible. However, at these scales, the competition or cancellation of new type of interactions can give rise to exotic phases of matter with unusual characteristics. The goal of the project Unconventional Phases of Ultracold Quantum Matter with Competing Interactions (UltraComp) is to investigate novel phases in ultracold atoms originating from the interplay between the mean-field interactions with either kinetic energy (modified by spin-orbit coupling) or with intrinsic quantum fluctuations. The proposed state-of-the-art experiments will focus on the study of three novel phases with unconventional properties: the supersolid, the ultradilute quantum droplet and the supersolid-like liquid. The study of these novel phases will help to deepen the understanding of beyond-mean-field effects in many-body systems. At the same time, the project will provide deep insight on supersolidity, thus impacting condensed-matter physics at large.

Mots clés : ultra cold atoms, quantum liquids, quantum fluctuations, quantum mixtures, spin orbit coupling, supersolidity, collective excitations, dipolar gases

Participants :
- Institute of Photonic Sciences (Espagne) — Coordinator, beneficiary, Recherche, subvention : 172932.48 €
Projet ChildEmp (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

The phenomenon of empathy is receiving growing interest in the European public sphere and scientific community. In particular, the question of how one learns to feel empathy towards the environment and the beings which inhabit it has been identified as a key issue to address at this time of environmental crisis.The proposed project investigates how empathy is learnt by children from an Amazonian indigenous community in Ecuador. It explores how and under what circumstances indigenous children in the Ecuadorian Amazon learn to perceive nonhuman entities as human-like and develop empathy towards them. Grounded upon my extended ethnographic knowledge of the region, the project will contribute to broader contemporary debates of how empathy towards nonhumans is culturally acquired, manifested and actively learnt during childhood. This is a social anthropology project with a strong interdisciplinary approach which includes perspectives from developmental psychology, ecology, cognitive science and philosophy. The aims of this project are: 1. to explore how children learn to perceive others as human-like in a setting which is inductive to such learning; 2. to explore children’s perception and understanding of nonhuman personhood and intentionality; 3. to understand the nature of ‘empathy’ among indigenous Runa people of the Ecuadorian Amazon. These aims will be reached through 10 months of ethnographic fieldwork in an indigenous Runa village where I will deploy participant observation and other methodologies from psychology, medical and visual anthropology which will be designed during pre-fieldwork training at the University of Kent. Research results will be disseminated through an academic and public engagement plan which includes two academic publications, an ethnographic film, a secondment at the Centre for Subjectivity Research in Copenhagen, a workshop and a document to be used by community members for school policy-making.

Mots clés : children, empathy, amazonia, indigenous people, ecuador

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

The physics of charge and spin transport is the basis of current consumer devices. Recent discoveries in solid-state physics have highlighted the importance of the coupling of the electron’s motion to its spin for transport phenomena. However, our understanding of transport with this so-called spin-orbit coupling has been largely limited to non-interacting systems, even though the first experimental systems with well-controlled spin-orbit coupling and interactions are already available. Here, we aim to provide a theoretical description of these novel interacting spin-orbit coupled systems. More concretely, we will derive equations describing the motion of spin and mass, and solve these equations. We will investigate spin transport in the uncharted regime where the inter-particle interactions compete with spin-orbit coupling. In particular, we will quantify the robustness of the familiar transport phenomena (e.g., the spin Hall effect) in the presence of interactions. The group of Prof. Juzeliunas is at the forefront of spin-orbit coupling physics. The group of Prof. Stringari is one of the leading groups in the world when it comes to collective excitations of the many-body system. Combining their expertise with my quantum transport proficiency will allow to obtain, for the first time, a transport theory of interacting quantum gases with spin-orbit coupling, and provide its predictions as a collective excitation spectrum, which is directly accessible by ultracold-atom experiments. A successful accomplishment of this aim will open up the possibility to push spin-dependent transport phenomena to new regimes.

Mots clés : ultracold atoms, spin transport, spin orbit coupling, quantum degenerate, bose gas

Participants :
- Vilnius University (Lituanie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 130779.6 €
Projet DOMINO (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

The planning and construction on or in soft marine clays has been proven to remain a challenge for geotechnical engineering. These type of clays are often instable, difficult to characterize and reinforce (i.e. ground improvement), and very common in coastal areas all over the world. The presence of marine soft clays are often the reason for landslides, with hazardous consequences. The complexity of these natural material has hindered the understanding of how macroscopic properties (>meters) such as instability, translates to microscopic (<micrometer) phenomena. As a result, the complex behavior of marine soft clays observed on the continuum scale is not fully understood and the models based on this experimental data are phenomenological. Yet, it is the properties and processes occurring on the microscale that govern the material response properties of these clays. This proposal aims to develop a multiscale framework for investigating marine soft clays. The objectives to reach this aim are the development of an anisotropic aggregation model for clay, the development of simple model materials with well-defined chemical and mechanical properties, and the comparison of these simplified models with naturally occurring soft marine clays. The proposed research use concepts from aggregation theory in combination with simulations of macroscopic material properties such as stiffness, strength and permeability. Experimental methods consists of state-of-the-art material characterization techniques such as: Nuclear Magnetic Resonance Relaxometry, Time-Resolved Dynamic Light Scattering, chemical analysis methods and mechanical characterization using advanced Bishop Wesley cells. The planned work is a bottom-up approach, where simple model materials substitute the natural more complex ones and aid the development of multiscale soil constitutive models.

Mots clés : marine soft clay, sedimentation, aggregation, nuclear magnetic resonance

Participants :
- Chalmers University of Technology (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 185857.2 €
Projet FLUOROKEF (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

The potassium efflux system, Kef, protects bacteria against the detrimental effects of electrophilic compounds via acidification of the cytoplasm. Its vital role in maintaining cell homeostasis makes Kef a promising target for antibiotics, but such drugs can be developed only with a molecular understanding of Kef activation. Our work indicates that phenylalanine residue 441 (F441) in Escherichia coli is crucial for the activation of K+ efflux. This mechanism is conserved, and F448 of Shewanella denitrificans Kef (SdKef) has the same function. This work employed X-ray crystallographic studies using a truncated construct of the E. coli Kef soluble C-terminal domain (EcKefCTD) and biophysical studies conducted on the SdKef C-terminal domain (SdKefCTD). While the crystallographic studies have been essential in hypothesis generation, they lack the dynamic aspect that is required to understand the mechanism of Kef activation. Although the use of a truncated construct has allowed development of biophysical assays, we wish to extend our work to focus on the full-length channel. To achieve these aims we will employ whole cell 19F NMR to probe the function of Kef. To determine if 19F NMR can be used to monitor F448 conformation, we will employ amber stop codon technology to replace F448 of SdKef with 4-trifluromethyl-L-phenylalanine (tfmF). We will monitor the dynamics of F448tfmF by 19F NMR upon binding of activators and inhibitors, using our library of SdKef ligands. To gain an understanding of Kef activation in cells, we will quantitatively determine binding affinities of the Kef ligands to SdKef(F448tfmF), in E. coli transformants using in-cell 19F NMR. This direct determination of binding inside the cells will be more physiologically relevant than the in vitro KD data. To assess the antibiotic activity of compounds that show cellular activity against Kef, we will employ the Kirby-Bauer disc diffusion method to screen for compounds that can kill bacteria.

Mots clés : bacterial potassium channels, unnatural amino acids

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

The precise expression of protein coding genes is of crucial importance to all organisms, since proteins are involved in virtually all vital processes. Some proteins need to be available at exactly the right amount to perform cellular functions sustainably and thereby maximize fitness. Consequently, gene expression needs to be accurately controlled. For these reasons, it has been hypothesized that cells evolve towards a state in which expression levels are optimally tuned to maximize fitness in the current environment. The cell’s growth and resource distribution is constrained by tradeoffs between the costs and benefits of a particular expression level. Recent investigations of the global effects of protein levels provide insights into the mutual dependency between expression and growth. To test this central hypothesis in systems biology, we use Escherichia coli which is the best-characterized model organism for fundamental research on gene expression, as well as for biotechnological applications. We aim to advance the understanding of the costs and benefits of expression by systematically investigating its ~4000 genes with gene deletion- and expression libraries. The effect of the expression level for each gene on fitness will be quantified through precise high throughput growth rate measurements. We will dissect general cellular cost-factors from gene specific effects which allow us to systematically uncover the mechanistic causes of the cost of protein overexpression. The burden manifests in universal protein biosynthesis costs but also specific costs such as eventual detrimental effects. The benefits are determined by the function of a protein: metabolic activity, structural component, and other roles. We will test if these contributions collectively converge to an optimum to maximize fitness. Optimality is a common objective in man-made systems and engineering and it will be intriguing to learn how natural selection has shaped cells according to this concept.

Mots clés : systems biology, quantitative microbiology, optimality, gene expression, precise growth rates, control analysis, e coli

Participants :
- University of Cologne (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 171460.8 €
Projet StressPFCog (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The prefrontal cortex (PFC) is a locus for higher-order cognition and executive control across species. In most mental disorders such as depression or schizophrenia, dysfunction in PFC and its related neuronal networks has been associated with a variety of cognitive impairments. Chronic stress exposure and abnormal levels of glucocorticoid stress hormone (GCs) is a key environmental risk factor for psychiatric illness. The PFC is highly vulnerable to stress exposure and many studies have reported detrimental effects of chronic stress exposure and/or high GCs levels on cognition, however the physiological underpinnings remain poorly understood. GCs exert their action in part by binding the glucocorticoid receptor (GR), a transcription factor expressed in every cell type. Through a complex interplay with co-factors, GR can modulate the expression of a large set of genes and thereby modify brain circuit physiology ultimately leading to behavioural changes. In this project, I propose to investigate the molecular and cellular mechanisms through which stress-exposure can modify the activity of PFC and its related networks and lead to cognitive impairment. Combining viral-mediated gene transfer and conditional mutagenesis in mice, I propose to inactivate GR either within the whole PFC or in discrete PFC cell populations namely the pyramidal neurons or the parvalbumin-expressing interneurons. I will study the impact of these manipulations on cognitive function including working memory and behavioural flexibility under basal conditions or after chronic stress exposure. The physiological correlates of cognitive deficits will be investigated using multisite electrophysiology recordings in behaving mice with a specific focus on PFC-hippocampus-midbrain circuits. Finally, I propose to examine the PFC-specific role of an important GR binding partner called BRG1, a chromatin remodeler recently linked to cognitive decline in several psychiatric conditions.

Mots clés : stress, cognition, prefrontal cortex, glucocorticoid receptor, chromatin remodeller

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 173076.0 €