Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet FREEMIND (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Neuromorphic computing such as deep-learning algorithms arise as a promising solution to treat the exploding amount of data generated worldwide, but at the cost of expensive time and energy budget on conventional hardware. There is an urgent need for a low-power, compact neuromorphic chip that can support bio-inspired computing: a network of cells collocating storage (non-volatility) and computing (synaptic plasticity). This work proposes to achieve such cell using a ferroelectric resistor, down-scaled to nanometer thickness to allow direct electron tunneling through the ferroelectric barrier (ferroelectric tunnel junction): the learning functionality (i.e. synaptic plasticity) will be implemented through the control of the distribution of the (non-volatile) ferroelectric domains. The fellow will bring her expertise in ferroelectric tunnel junctions and will combine it with IBM’s expertise in device and circuits integration and characterization, making use of the state-of-the-art equipment offered by their research center. In order to accelerate the creation of an end-to-end neuromorphic device, she will lead a collaboration with ETH Zurich and will benefit from their expertise in predictive physics-based modeling. The research project will aim at: (i) the demonstration of a non-volatile and plastic ferroelectric “synapse” made of Hf0.5Zr0.5O2 – a fully CMOS-compatible material, (ii) the development of models of individual cells and of a neural network and (iii) providing design guidelines for neuromorphic hardware based on this technology. The outcome will be to evaluate performances not only of individual synapses but of a neural network as a whole. Through the Action, the fellow will not only aim at creating a novel technology; but also at leading an interdisciplinary research project uniting complementary actors for an innovative solution to a society challenge.

Mots clés : ferroelectricity, tunnel junctions, memristors, bio inspired, neuromorphic hardware, neural networks, physics based modeling, finite element method, deep learning, microelectronics

Participants :
- IBM Research - Zurich (Suisse) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 191149.44 €
Projet MUMDUPSC (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Neuromuscular Diseases (NMDs), affecting both children and adults with a prevalence of 1 in a 1000 people, form a large and heterogeneous group of genetic diseases causing progressive degeneration of skeletal muscles. Most NMDs result in chronic long-term disability imposing a significant burden on patients, families and public health care. In many cases, patients die prematurely from respiratory, and in some cases cardiac, muscle impairment. There are more than 200 NMDs, including over 30 types of Muscular Dystrophy (MD) which results from the mutation of genes controlling muscle functions and structures. The classification of MDs is not fixed but evolves with the constant discovery of new genes/mutations responsible for these diseases. Despite more than 40 genes involved in MDs have already been identified many genes are still to be discovered. In Europe, thousand patients with MD are currently without molecular diagnosis. Delayed or inaccurate diagnoses postpone the adequate care and may have irreversible consequences for the patients. MUMDUPSC aims combining descriptive clinical diagnosis, genomics and disease modelling from patients’ induced Pluripotent Stem Cells (hiPSC) to identify both molecular mechanisms and genetic mutations underlying undiagnosed muscular dystrophies (UMDs). Specifically, I propose to generate hiPSC from selected UMD patients and investigate their transcription profile during skeletal muscle differentiation compared to control cells (unaffected or affected with known MDs). By identifying, for the first time, DEGs specifically modulated in UMDs, MUMDUPSC will reveal the genes and pathways specifically contributing to the diseases. It will represent a proof of concept for the classification of unlabeled muscle pathologies and, in the long term, will provide innovative leads for the diagnosis and the treatment of these debilitating diseases.

Mots clés : muscular dystrophy, patients  hipsc, diagnosis, transcription profile, whole genome sequencing

Participants :
- Aix-Marseille Université (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 196707.84 €
Projet BRAIN REPEATS (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Neuropsychiatric disorders such as dementia and depression are among the leading causes of disability and exert a dramatic burden on Europe’s healthcare systems. In order to devise more effective therapies it is essential to elucidate their genetic basis. However, to date genetic association studies have only identified a small fraction of the genetic determinants, possibly due to neglect of some important genomic variations, especially DNA repeat expansions. Expanded DNA repeats above a certain threshold are associated with various neurological disorders, the most common of which are polyglutamine diseases caused by exonic triplet (cytosine-adenine-guanine (CAG)) repeat expansions leading to a range of cognitive and psychiatric abnormalities. Emerging findings indicate that even CAG repeat length variations in the normal range in polyglutamine disease-associated genes (PDAGs) can affect mental health and cognition. Nevertheless, virtually nothing is known about the biological mechanisms through which these genetic variations affect brain structure and function. Therefore, the key objective of this proposal is to evaluate the effects of CAG repeat polymorphisms in PDAGs on brain structure and function, both in healthy controls and carriers of the mutation for Huntington disease (HD), the most common polyglutamine disease. To this end I will: 1) Systematically assess the association between these genetic polymorphisms and mental health, cognition and brain morphometric and functional MRI imaging in a large cohort of well-characterized control subjects and HD mutation carriers, and 2) Perform pathway analysis using gene expression data already available from these participants in order to elucidate the underlying molecular pathways. This proposal is unique as it translates novel insights into the pathophysiology of polyglutamine diseases to those of more common, complex disorders, thereby accelerating development of effective therapies for all patient groups.

Mots clés : huntington disease, cag repeats, polyglutamine disorders, depression, dementia

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 97727.4 €
Projet ENCORE (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

Neutrinos are the most promising sector where to look for something new in particle physics. Neutrino properties can be studied using two different approaches: with terrestrial experiments or complementary probes, such as cosmology. In this proposal we will explore both possibilities. Concerning terrestrial experiments, we will consider the problems related to the theoretical calculation of the flux of reactor antineutrinos, in light of the recent reactor anomalies and the so-called 5 MeV bump. The results will be applied to constrain the three-neutrino mixing parameters and the properties of a potential light sterile neutrino that could explain the short-baseline anomalies. A new calculation of the reactor antineutrino spectra will also have direct applications to the monitoring of nuclear power plants to prevent the development of nuclear weapons, following the efforts of the International Atomic Energy Agency. Considering cosmology, we will study the dynamics of light sterile neutrinos in the early Universe and its implications for future experimental results, as well as the clustering of relic neutrinos in the Milky Way and the consequences for their direct detection. The obtained results will be compared with all available experimental data in order to improve the current constraints on neutrino properties. Dissemination will be implemented through the publication of articles in high-impact journals, contributions to international conferences and outreach activities, including blog articles, a YouTube video and participation in open-door initiatives at the host institute. The strong network of collaborations, the importance of the treated aspects and the timeliness of the results, well justified by the current status of experimental results and the need of more precise theoretical calculations for the incoming ones, will reinforce the leading position of Europe in the international scientific community devoted to neutrino physics.

Mots clés : early universe, relic neutrinos, neutrino clustering, nuclear reactors, sterile neutrinos, short baseline anomaly

Participants :
- Spanish National Research Council (Espagne) — Coordinator, beneficiary, Recherche, subvention : 158121.6 €
Projet NEUTRO-LILR (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Neutrophils provide the first-line of antimicrobial defence and orchestrate inflammation. They are tightly regulated by ligand-receptor interactions to ensure pathogen clearance and to prevent host damage. Targeting receptors, with natural or synthetic ligands, that control neutrophil functions is a promising strategy to control infections and inflammation. However, basic knowledge on the role of certain receptors in neutrophil biology, and their interactions with pathogens, has been neglected. This includes leukocyte immunoglobulin-like receptors (LILRs), a family of surface receptors that are potent regulators of immune cell activity and potential targets of immunotherapeutic strategies. The major aim of this project is to comprehensively understand how LILRs regulate neutrophil functions, to identify bacterial ligands of LILRs and to test whether each bacteria-derived LILR ligand has pro- or anti-inflammatory properties that could be exploited in future immunotherapeutic strategies. For the first time, we will extensively characterise the functional role of four representative LILRs in controlling neutrophil functions. We will screen our newly developed high-throughput bacteria secretome phage display libraries, representative of 20 pathogens and the entire human gut microbiome, for identifying bacterial molecules that bind to LILRs. Finally, we will determine whether each of the ligands acts as a LILR agonist or antagonist. These experiments build upon expertise and preliminary results of the applicant, and upon unique resources of the host. The proposed experiments will expand knowledge of the function of poorly studied LILRs on neutrophils. This will advance knowledge of neutrophils, immune responses and bacterial pathogenesis, paving the way for identifying new strategies for treatment of infection and inflammation.

Mots clés : neutrophils, immune receptors, host pathogen interactions, staphylococcus aureus, escherichia coi

Participants :
- University Medical Center Utrecht (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 165598.8 €
Projet ORTHOCAT (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

New cancer care methodologies with fewer side effects and no need for major surgery are required to enhance patient wellbeing. Photodynamic Therapy (PDT) partially accomplishes such mission employing light and a photosensitizer. Nevertheless, the PDT mechanism of action intimately depends on oxygen, which limits its efficacy, particularly in hypoxic solid tumours. Promising strategies to improve the impact of PDT in the clinics currently involve the design of photoactivatable transition metal complexes, a class of compounds which combines the rich photochemistry of metal complexes with the vast background of metal-based drugs in cancer therapy. In this framework, ORTHOCAT proposes an original and multidisciplinary strategy to exploit the efficiency and selectivity of riboflavin as unconventional photocatalyst for the activation of Pt(IV) anticancer prodrugs (Chem. Sci. 2017, 8, 4619). The project aims at designing novel riboflavin-based catalytic systems capable of activating Pt(IV) anticancer prodrugs inside the mitochondria of tumour cells. In particular, I will use triphenylphosphonium targeting vectors to develop new photocatalytic prodrug systems and delivery nanoplatforms which selectively accumulate in the mitochondria. Once in the organelle, riboflavin will act as singlet oxygen photosensitizer for PDT and simultaneously as photocatalyst to generate Pt(II) species for targeting mitochondrial DNA (photochemotherapy). Imbalance of mitochondrial delicate redox homeostasis by ORTHOCAT dual agents can trigger cell death through convenient cellular pathways. Therefore, ORTHOCAT prodrug systems will synergistically kill cancer cells with increased effectiveness, while potentially reducing side effects of metal-based drugs. Successful outcome of the project has the potential to deliver innovative therapeutic agents for cancer photochemotherapy.


Participants :
- Donostia International Physics Center (Espagne) — Coordinator, beneficiary, Recherche, subvention : 158121.6 €
Projet DEEPLEARNRBP (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Statut du projet : CLOSED

New technologies have revolutionized our understanding of RNA binding protein (RBP) function. Global screens for RBPs have pulled down hundreds of proteins for which no discernable RNA Binding Domain is present. These proteins, termed enigmRBPs due to their enigmatic nature, do bind RNA in unknown and variable fashion. An ever increasing number of such RBPs are having their target sites identified via CrossLinking and ImmunoPrecipitation Sequencing techniques (CLIP-Seq). This torrent of data can be harnessed by novel Deep Learning techniques to identify high order characteristics of RBP function. The aim of this proposal is the development of a machine learning model that can explore the functional implications of RBP binding characteristics. A model that, given an enigmatic RBP, can identify other known RBPs that show similar binding characteristics, such as sequence motifs, conservation motifs, secondary structure motifs, and higher order combinations of the above. We will focus on methods to practically interpret the machine learning model to biological knowledge, especially higher order filters that can learn the interplay among varied input, such as secondary structure, sequence and conservation. Beyond the theoretical, we will disseminate our methods in easy to use, standalone and web application format, in order to increase the practical application of our research. We are transplanting expertise from the bioinformatics and machine learning field, into a fertile substrate of RNA biology and CLIP-Seq experimentation. This interdisciplinary project will involve close collaboration and two-way transfer of knowledge in a dynamic research environment.

Mots clés : rna binding proteins, clip seq, deep learning

Participants :
- Masaryk University (Rép. Tchèque) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 156980.64 €
Projet Mobiclock (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

New types of atomic clocks, based on laser-cooled and trapped atoms interrogated by optical lasers, are changing the paradigm for precision measurement of time and frequency. Optical lattice clocks, which provide superb frequency stability, are today complex systems, able to operate only in well-controlled laboratory environments and require continuous personnel intervention. The proposed activity aims to realize the transition from today's laboratory systems into mature mobile instruments. The result of this transition opens outstanding and transformational future fields of application: world-wide accuracy comparisons of stationary clocks, high-precision tests of General Relativity, and mapping of the Earth gravitational potential via relativistic geodesy. Towards this goal, the ER will develop a robust and mobile optical lattice clock based on strontium atoms, exhibiting ultra-high performance. He will pursue three objectives: 1) improved subsystem for cold atomic sample preparation and improved interrogation laser; 2) demonstration of inaccuracy and instability at 1x10^-17 level; 3) demonstration of transportability and repeatability of ultra-high performance. These objectives will be achieved, respectively, via a new approach for simplified and more robust laser cooling and trapping of the atoms, via an advanced reference cavity design, and implementing sub-systems for better control of systematic effects. Within a European cooperation a full characterization of the clock before and after transportation will take place during visits to metrology institutes. The match of the experienced researcher and the supervisor in terms of scientific background, common research and technology interests, and international networking is unique and offers the opportunity to maintain Europe at the forefront of the development and application of transportable optical clocks.

Mots clés : optical atomic clocks, ultracold atoms, optical frequency measurements, relativistic geodesy

Participants :
- Heinrich Heine University Düsseldorf (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 171460.8 €
Projet NanoMop (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Niemann-Pick Disease Type C (NPC), also known as “childhood Alzheimer’s”, is a rare genetic disorder caused by the accumulation of cholesterol particularly in the brain with subsequent cognitive and mobility decline. In the EU NPC has an incidence of 1 per 100,000 people. Most cases are detected during childhood and progress to cause life-threatening complications by the second or third decade of life. Cyclodextrins (CDs), a family of naturally occurring sugars, have recently gained considerable attention as a potential therapeutic intervention in the treatment of the disease because of their capacity to sequester cholesterol. Although promising, the current treatment of NPC based on a chemical modification of bCD suffers from poor pharmacokinetics and bioavailability in the brain. In this project I propose a new interdisciplinary approach in which bCDs will be embedded into a novel class of smart polymer nanoparticles (NanoMops) that could overcome these limitations. The project addresses an important question that needs to be answered urgently and its successful completion will contribute to the treatment of the neglected disease in line with the Horizon2020 health goal of providing better and more effective therapies. My specific skillset in chemical modification of CDs puts me in a unique position to successfully carry out this project. This interdisciplinary proposal is designed to provide me with advanced training in macromolecular chemistry and in a range of cutting-edge biological techniques. The fellowship will significantly diversify my competences and broaden my profile – professionally and personally - enabling me to pursue a career as an internationally recognised independent researcher. The project will also create new important international and inter-sectoral partnerships with excellent academic and industrial players while reaching out to charity organisations, raising awareness and networking researchers and key stakeholders in the area of NPC

Mots clés : cyclodextrins, polymers, nanoparticles, niemann pick disease type c

Participants :
- Istanbul Technical University (Turquie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 145845.6 €
Projet EXNADMINA (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in industrialized countries, including Europe, and comprises a spectrum of disorders ranging from hepatic lipid accumulation (steatosis) to inflammation (non-alcoholic steatohepatitis, NASH) and fibrosis. Pathogenic pathways leading from hepatic steatosis to NASH are still incompletely understood resulting in a lack of approved therapeutic options besides life style changes. Physical activity is effective to prevent NAFLD progression. The mechanism of exercise action on liver mitochondrial metabolism is not clear yet. However, exercise might exert its positive effects via increasing hepatic nicotinamide adenine dinucleotide (NAD) levels. Several studies showed that the hepatic NAD metabolism is dysregulated during the development of NAFLD and that exercise has a positive effect on NAD metabolism and function of NAD dependent enzymes in skeletal muscle. The functionality of mitochondrial metabolism is highly dependent on the maintenance of the organellar NAD pool. Mitochondrial dysfunction has been implicated in the progression from steatosis to NASH. We hypothesize that a dysregulated NAD metabolism in the liver is involved in the development of hepatic mitochondrial dysfunction in NAFLD/NASH. Our overall aim is to define the impact of exercise on hepatic mitochondrial dysfunction and test whether exercise effects are mediated via restoration of NAD metabolism. We will achieve this by combining the knowledge on hepatic NAD metabolism of the fellow with the expertise in exercise mouse models and on analysis of mitochondrial function of the Supervisor. This study is one of the first to comprehensively examine the interaction between exercise, mitochondrial dysfunction as a cause of NAFLD and NAD metabolism specifically in the liver and in hepatocytes and ultimately aims to identify novel therapeutic targets for the prevention and treatment of NAFLD.

Mots clés : non alcoholic fatty liver disease, exercise rodent model, nicotinamide adenine dinucleotide, hepatic insulin resistance

Participants :
- University of Birmingham (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 146591.1 €