Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet LENSD (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Two-dimensional (2D) nanomaterials have received significant attention over the past decade due to their remarkable material properties. Graphene is the most frequently studied, however a range of other 2D materials such as molybdenum disulfide and boron nitride have also demonstrated properties which will help society advance in areas from opto-electronics to sustainable energy. One of the biggest challenges currently facing 2D nanomaterials is scalable production. Current exfoliation processes are insufficient for industrial scale production due to high energy requirements, poor yield (typically < 5 wt%), introduction of material defects and low production rates (< 6 g/h). This project aims to address these process limitations. A novel liquid exfoliation approach will be investigated, using continuous flow over a spinning disc to create mono- and few-layer materials. The research activities will provide a new holistic insight into shear-induced liquid exfoliation, by experimentally and numerically examining how the fluid mechanics and multiphase transport phenomena over the spinning disc affect material characteristics at the nanoscale. The investigation involves cooperation between multiple disciplines. Experiments include the optical techniques of infrared thermography, high-speed imagery and particle image velocimetry. The researcher will receive extensive training in advanced numerical methods for simulating thin liquid films and interfacial flows at Imperial College London. Training in microscopy techniques will also be completed for the measurement of nanosheet defects and size. These research activities will assist the development of future liquid exfoliation technologies and are aligned with personalised actions to advance career development. The fellowship will broaden the researcher's technical and complimentary expertise, and facilitate inter-sectoral mobility from thermal to chemical engineering, nanotechnology and process intensification.

Mots clés : fluid mechanics, thermal sciences, multiphase flows, thin liquid films

Participants :
- Imperial College London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet Beta-splicenet (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Type 1 diabetes (T1D) is a chronic autoimmune disease in which pancreatic beta cells are killed by infiltrating immune cells and by cytokines released by these cells. The mechanisms by which autoimmunity is triggered and aggravated in T1D and the nature of the intracellular signals that decide beta cell fate between survival or death remain to be clarified. Alternative splicing (AS) is a complex mechanism of gene expression regulation and a potent generator of proteome diversity. It provides cells with an exquisite capacity to rapidly modify their transcriptome and proteome in response to intra and extracellular cues. AS affects more than 90% of human genes and has a major impact in many cellular processes, including cell survival and generation of new antigenic epitopes. There is a growing interest in the role of AS in autoimmune diseases but nearly nothing is known on its role in beta cells and diabetes. Recent findings by the host group indicate that pro-inflammatory cytokines change the expression of >30 RNA-binding proteins (RBPs) and modify AS of >3000 genes in human beta cells. Importantly, the host group has discovered that the diabetes candidate gene GLIS3 affects beta cell apoptosis by regulating the splicing of the pro-apoptotic BH3-only protein Bim. These findings suggest that AS plays an important role in the regulation of beta cell dysfunction and death by mechanisms that remain to be clarified. We hypothesise that pro-inflammatory signals activate splicing networks contributing to beta cell functional lost and death. We propose in the present project a systems biology approach that will combine RNA-seq, network inference and analysis of individual RBPs to characterize and validate inflammation-activated splicing networks in beta cells. The ultimate goal is to identify key splicing networks and mRNA splice variants that will be targeted by splicing-modulation molecules as a novel therapeutic strategy to prevent progressive beta cell loss in T1D.

Mots clés : type 1 diabetes, pancreatic beta cells, alternative splicing, rna binding proteins, rna regulons, apoptosis

Participants :
- Université Libre de Bruxelles (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 160800.0 €
Projet BETA-BACT (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Type 2 diabetes (T2D) has risen to epidemic proportions resulting in major morbidity and mortality. In addition to insulin resistance (i.e. impaired insulin action), impaired function and destruction of the insulin-producing beta cells form the direct cause for hyperglycemia and T2D, and causes the progressive course of disease. As such, due to continuous beta-cell destruction, many patients require treatment with exogenous insulin therapy. Clearly, therapies that may halt or reverse this detrimental process are warranted. An inflammatory process in islets of Langerhans, with infiltration of immune cells and a central role for toll-like receptors (TLR), is present in T2D, however, the primary trigger for this inflammatory response remains unknown. Recently, (diet-induced) alterations in intestinal microbiota composition were shown to associate with T2D. In addition, T2D patients have increased translocation of detrimental bacteria (‘leaky gut’), previously shown to induce adipose tissue inflammation and dysfunction. Recently, I hypothesized that increased bacterial translocation to the pancreas induces inflammation and beta-cell dysfunction in T2D through TLR related mechanisms. I addressed this hypothesis first by identifying translocated microorganism DNA in pancreatic tissue harvested during pancreatectomy in patients with and without T2D. In pilot data, I have demonstrated increased bacterial load in patients with T2D as compared to control patients. The involved micro organisms with highest pathogenicity will be (an)aerobically cultured and subsequently used in gavage studies in a obese mouse model with or without a knockout for TRL4 to study their effects effects on beta-cell function, glucose metabolism and pancreas inflammation.


Participants :
- Vrije Universiteit Amsterdam (Pays-Bas) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Amsterdam University Medical Centers (Pays-Bas) — Coordinator, beneficiary, Recherche, subvention : 167610.6 €
- University of British Columbia (Canada) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet Targeting TopoII (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Type II topoisomerase (TopoII) metalloenzymes are crucial in regulating DNA topology in replication, transcription, recombination, and repair processes. TopoII is thus a validated target for clinical antibiotics and anticancer drugs. Recent high-resolution X-ray structures of the TopoII/DNA complex showed multiple metal ions bound to the TopoII active site. On the basis of these novel findings, a unified two-metal-ion reaction mechanism for TopoII catalysis has been proposed. However, it is still not clear how this Mg-aided two-metal-ion mechanism permits TopoII to cleave and relegate back DNA strands. Building on our previous studies on metalloenzymes, we seek here to clarify TopoII’s two-metal-aided enzymatic mechanism and identify novel TopoII inhibitors, thus completing the proposer’s computational skill set, boosting her chances of establishing and leading soon an independent computational group. We propose two objectives: First, we will depict the reaction path connecting the enzymatic reactants and products in TopoII. We will achieve this using state-of-the-art computational methodologies such as molecular dynamics (MD) and hybrid quantum mechanics/molecular mechanics (QM/MM) simulations coupled to enhanced sampling techniques for free-energy estimates. We will thus elucidate the metal ion dynamics in TopoII catalysis, together with the metal-induced structural changes that affect the reactivity and efficiency of TopoII catalysis. Importantly, we will investigate TopoII catalysis in the presence of either the catalytic Mg or inhibitory Zn ions in the catalytic pocket. Secondly, we will integrate mechanistic insights on TopoII catalysis with the recent structural and biophysical data on TopoII to decipher drug resistance and identify new TopoII inhibitors. To this end, docking and MD simulations will be used to facilitate the discovery of potent TopoII inhibitors as a first step toward more effective anticancer drugs and new, urgently needed antibiotics.

Mots clés : topoisomerase, enzymes, structure based drug discovery, anti cancer, antibiotic, molecular, dynamics, metadynamics

Participants :
- Italian Institute of Technology (Italie) — Coordinator, beneficiary, Recherche, subvention : 180277.2 €
Projet REMAKIN (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Type-2 diabetes (T2D) is a chronic condition strongly associated with cardiovascular diseases, mainly recurrent myocardial infarctions (MI), and generating enormous healthcare cost. Macrophages orchestrate the remodelling of the heart post-MI by efferocytosis-mediated cytokine secretion. Specifically, Mertk-mediated efferocytosis promotes vessel formation, tissue reperfusion and resolution of the inflammatory response via the secretion of the anti-inflammatory cytokines interleukin-10 (IL-10) and Vascular Endothelial Growth Factor-A (VEGF-A). In IR/T2D, efferocytosis-mediated cytokine secretion is impaired, leading to chronic inflammation, adverse post-MI remodelling, recurrent heart failure and excessive mortality. To date, the signalling and intracellular trafficking pathways leading to cytokines secretion are unknown, and the mechanisms of impairment during IR/T2D are unexplored. Previous therapeutic strategies focussed on repairing damaged tissue by injection of progenitor cells or modulating inflammation by cytokine injection, but both strategies gave disappointing results. In this proposal, I will define the mechanisms of efferocytosis-mediated cytokine secretion in macrophages, investigate their defects in IR/T2D and test a novel cell-based therapeutic strategy for improving recovery of T2D patients post-MI and preventing recurrence of cardiac events by restoring cytokine secretion in diabetic macrophages.

Mots clés : insulin resistance, type 2 diabetes, myocardial infarction, inflammation, immunomodulation, macrophages, efferocytosis, regulated secretion, intracellular trafficking, cytokines

Participants :
- Institut national de la santé et de la recherche médicale (France) — Coordinator, beneficiary, Recherche, subvention : 196707.84 €
Projet KILLINGTYPHI (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Typhoid fever is a life-threatening systemic infection that continues to be a serious global health concern, claiming the lives of over 200,000 patients every year. It is caused by the intracellular bacterium Salmonella Typhi, a human-adapted pathogen unable to infect species others than humans. The molecular mechanisms underlying S. Typhi infection are only partially understood. Spanò and Galán recently discovered an antimicrobial pathway that is required to restrict the growth of S. Typhi macrophages derived from mouse (a non-susceptible host) and contributes to S. Typhi host-restriction. Despite this finding, the exact mechanisms used by macrophages to kill S. Typhi as well as the role of these mechanisms in the adaptation to the human host remain unknown. Through this project, I will investigate the mechanisms used by non-permissive hosts to eliminate S. Typhi. I will combine my strong background in molecular microbiology with the world-renowned expertise of S. Typhi-host interactions of the receiving group to identify host genes required to kill S. Typhi. I will apply state-of-the-art technologies, including pooled shRNA screens coupled to next-generation sequencing and the novel and powerful CRISPR/Cas9 technology, supported by a network of local and international collaborators. Specifically, I will: 1) identify Rab GTPases required for S. Typhi killing, 2) identify novel factors involved in pathogen killing through an unbiased genome-wide screen, and 3) elucidate the role of well-characterized antimicrobial factors in the Rab32-dependent killing of S. Typhi. The results will reveal new strategies of host-defence and will extend our knowledge of the host immunity mechanisms controlling the growth of intracellular pathogens. They have the potential to identify new therapeutic approaches to treat typhoid fever.

Mots clés : salmonella typhi, typhoid fever, macrophages, host defence, shrna, crispr, cas9

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

Understanding how organisms adapt to the environmental perturbations, including those caused by human activity, is a key question in evolutionary biology. Some organisms appear to adapt more rapidly than expected, and two factors predicted to contribute to this are environmentally sensitive epigenome regulation and transposable element (TE) activity under stress. Recent molecular studies have shown how interactions between the epigenome and TEs can affect genome evolution in the fruitfly Drosophila melanogaster. However, little is known about how these processes interact in natural populations, limiting our understanding of their role in population adaptation under environmental change. Environmentally sensitive interactions between the epigenome and TEs are underpinned by dynamic chromatin states regulating gene expression. Understanding how chromatin varies across populations and how responsive it is to environmental change is key to evaluating the role of epigenome-TE interactions in adaptation. Here we will measure natural variation in chromatin accessibility in different populations of D. melanogaster and look for associations between chromatin accessibility and polymorphic TEs. Proximate mechanisms (RNA and chromatin responses to stress) and phenotypic outcomes (life history traits) will be measured over multiple generations. Longer term evolutionary consequences will be measured in invasive and native populations of D. melanogaster and the more recently invading D. suzukii, and TEs associated with differential chromatin regulation in invasive populations will be validated using functional genomics techniques including CRISPR-Cas9. These data will reveal how interactions between chromatin states and TEs can shape adaptation over different organisational scales, from the molecular to the population-level, and across different temporal scales, including within-generation acclimation, transgenerational epigenetic change and long-term evolutionary change.

Mots clés : drosophila melanogaster, drosophila suzukii, environmental change, adaptation, invasive species

Participants :
- Spanish National Research Council (Espagne) — Coordinator, beneficiary, Recherche, subvention : 160932.48 €
Projet HopeQNet (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

Understanding how quantum effects can improve the performance of actual computing devices is an exciting and growing research area. However their role in neural networks (NNs), the complementary information process paradigm of classical computation is largely unexplored. The full translation of this paradigm at the quantum level ultimately requires to combine disordered spin-systems techniques, widely used in the study of classical NNs, together with the open quantum systems (OQSs) framework, in order to achieve their irreversible and non-linear dynamics. HopeQNet is the first step of an ambitious program that will lead, in a long term effort, to a new generation of quantum computing architectures, and is designed to deliver a first initial theoretical framework to investigate quantum effects in NNs, by considering the open quantum generalization of one of the most celebrated paradigms of NNs, the Hopfield model. This workhorse model will be simple and rich enough to: (i) apply well-developed tools from the theory of OQSs and establish a meaningful framework for a quantum NN; (ii) evaluate the potential gain due to quantum effects in this specific quantum NN architecture; (iii) engineering and modeling a proof-of-principle experiment of a Rydberg quantum simulator implementing it. HopeQNet combines the knowledge of the Applicant, who pioneered the use of disordered spin-systems in quantum many-body optical systems during his PhD (and will provide to the Host this unique expertise), together with the internationally recognized experience of the Supervisor in open quantum many-body systems and Rydberg atoms (who will mentor the Applicant throughout the training-through-research activity proposed here). This interdisciplinary combination of expertise is uniquely suited to carry out this first step of an ambitious 5-to-10 years program that will lead the Applicant to join one of the major EU institution working on quantum theory as an independent scientist.


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

Understanding how single neurons integrate and process incoming synaptic signals to generate a physiologically meaningful output remains a fundamental question in neuroscience. While much is known about how the integration of synaptic inputs is governed by overall dendritic geometry and ionic conductances along the dendritic membrane, the role of the micro-anatomical structure is yet to be deciphered. Although theoretical work suggests that structural details of dendritic spines might play a major role for synaptic function and dendritic integration, it has been experimentally difficult to address this long-standing hypothesis. While electron microscopy allows the visualisation of spine ultrastructure, it is incompatible with studying spine function in live brain tissue. I propose to combine state-of-the-art STED microscopy with holographic photolysis to examine the influence of spine morphology on dendritic integration of CA1 pyramidal neurons. STED microscopy will reveal spine morphology, while holographic photolysis will be used to stimulate multiple synapses at the same time with high spatio-temporal precision. This novel approach, relying also on electrophysiology and compartmental modelling, will make it possible to study the influence of nanoscale morphology on dendritic integration of multiple synaptic inputs. The project builds on my expertise in cell biology and neuroanatomy, and will give me the opportunity to master advanced opto-physiological methods in a host environment that is well known for bio-imaging and neuroscience. Given my strong background in neurodevelopmental disorders, the project will push the knowledge frontier on neuronal processing and will provide a framework for research into basic mechanisms of neurological disorders.

Mots clés : dendritic integration, dendritic spines, sted microscopy, holographic photolysis, computational neuroscience

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 173076.0 €
Projet ME-Optogen (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Understanding how the brain works is one of the grand scientific challenges of our times and constitutes a priority research line for the European Union. The study of the brain mechanisms that underlie fear learning and response is particularly relevant as it could provide the key to control anxiety disorders, with an associated high social and economic benefit for the European community. Recent studies indicate that specific areas of the amygdala, a structure located deep within the brain’s medial temporal lobe, are crucial for the generation of fear responses in mice. To gain more insight, it is now necessary to understand how individual neurons in these areas act and collaborate together to generate the appropriate response. Crucially, this requires the capability to observe and manipulate fear circuits in deep brain structures with single neuron resolution. However, reaching at the same time sufficient depth and high resolution represents a great experimental challenge. At present no technique exists that can enable such a study. The objective of the project is to overcome the current experimental limitations and develop a new optical method for the precise imaging and manipulation of neurons even deep in the brain of living animals. To this end we will extend advanced high-resolution optogenetic stimulation and imaging techniques to an optical micro-endoscope capable of reaching the desired depth in the brain of mice. Proof of principle experiments in vivo in the amygdala of mice will be performed. This highly multidisciplinary project, at the frontiers between optics and neuroscience, will require the great expertise of the host group in optogenetics methods, the strong background of the fellow in high-resolution optical techniques and the collaboration with an external advisor, expert in neurophysiology. The success of this research will provide new powerful tools to study the brain, thus potentiating the European competitiveness in this important field.

Mots clés : optogenetics, nonlinear microscopy, two photon stimulation, optical micro endoscopy, calcium imaging, holography, neural circuits, amygdala, in depth imaging

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