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

Atrial Fibrillation (AF) is the most common cardiac arrhythmia with an EU health cost of 13.5 billion annually. Despite the worsening that this cardiac arrhythmia provokes on the life quality of more than 6 million Europeans, AF therapies are suboptimal: success rate is below 60% including pharmacological and surgical approaches. AF is a multifactorial and progressive disease with high patient heterogeneity and therefore “the same treatment for all” is not optimal. GUIDE-AF addresses this challenge by a multi-sectorial and multidisciplinary research and training program in novel technologies for the individualization of the AF phenotype with the aim to increase treatments’ efficiency. GUIDE-AF will integrate data and knowledge from anatomical, biological, biomechanical and electrophysiological approaches to generate an accurate description of the patient-specific disease phenotype. The effect of the different AF treatments will be described and quantified for each AF phenotype in order to provide the best therapy choice. GUIDE-AF project will build a machine learning-based decision support system able to characterize the disease state and progression and able to predict the outcome of therapies. This algorithm will be based on technologies co-developed and validated by the candidate and the host and beneficiary research groups. GUIDE-AF will count with experts in cardiac arrhythmia management, AF characterization through image and signal analysis, basic and clinical research, as well as access to one of the largest AF patient database. GUIDE-AF will have an eminently multidisciplinary and clinical approach and will focus on providing a feasible and implantable solution for increasing the therapy success and reducing human and health system costs. This proposal includes intensive training for the candidate in new advanced technologies for cardiac characterization and disease profiling, as well as knowledge transfer from and to the host and beneficiary institutions.

Mots clés : atrial fibrillation

Participants :
- Stanford University (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- University of Valencia (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 204415.68 €
Projet SAECG (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Atrial fibrillation (AF) may be categorized as an epidemic disease associated with an increased risk for heart failure, thromboembolism, dementia and mortality. The underlying mechanisms behind AF describe multiple pathological states leading to various remodeling processes. One of the easiest available diagnostical tools is an electrocardiogram (ECG). Numerous P wave indices have been identified, demonstrating associations with increased risk for adverse cardiovascular outcomes and mortality. Prolonged signal-averaged P wave duration (SAPWD) measured from the non-invasive signal averaged electrocardiogram (SAECG) using a vector composite of filtered orthogonal leads accurately measures cardiac activation times. In comparison with analysis of a standard 12-lead ECG, the SAECG is superior in detection of P wave prolongation as a risk marker for AF. However, there are only limited data analyzing this issue. Current project is aimed to perform P wave SAECGs in Framingham Heart Study (Boston, US) and LIFE Health Care Study (Leipzig, Germany) and to investigate their role in AF incidence. Furthermore, estimation of corresponding lifetime risk will be performed using multistate modeling phenomapping of AF, e.g. classification of AF patients based on a broad range of data (clinical, laboratory, ECG, echocardiography, biomarkers) predicting adverse clinical outcomes. The current project represents an innovative and authentic multidisciplinary research in AF and includes different future perspectives. It paves the way for fruitful international cooperation with Framingham cohort - the one the most renowned epidemiological studies, intensive exchange of experience and researcher mobility as well as academical and practical implementation of cardiovascular epidemiology and prevention at European institution.

Mots clés : atrial fibrillation, electrocardiography  ecg, pr interval, p wave indices, risk stratification, endophenotype, epidemiology, prevention, biomarkers

Participants :
- Leipzig University (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 264669.12 €
- Boston University (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet PreCoASD (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Autism Spectrum Disorder (ASD) affects more than seven million individuals in the European Union. Yet, this neurodevelopmental disorder remains poorly accounted for. ASD is defined by persistent deficits in social interactions and communication, and by restricted interests and repetitive patterns of behaviors. Recent predictive coding theories offer potential accounts of ASD. The predictive coding framework assumes that the brain constantly generates predictions about its environment. These predictions, or priors, are integrated with sensory information to produce a percept, and their relative contributions depend on their precisions. A suboptimal balance of prior and sensory precisions could be at the core of ASD. Theories suggest low prior precision, high sensory precision and/or inflexible ratio of precisions in ASD. Empirical evidences are scarce, and this proposal aims at testing these theories. I aim at characterizing the behavioral and neural mechanisms underlying the estimation of prior (WP1) and sensory (WP2) precisions in ASD. In WP1, participants will perform a visual task designed to elicit the implicit learning of a prior with a high or low precision (quantifiable with computational models). The neural correlates of prior precision estimation will be investigated with functional and structural MRI, DTI, and magnetic resonance spectroscopy. In WP2, participants will be passively exposed to fast periodic visual stimulations. Using a sweep paradigm with visual stimuli changing in magnitude of low-level features, we will determine their perception thresholds from the EEG data. Sensory precision will be estimated from both EEG and behavioral measurements of perception thresholds. In WP3, I will integrate the results of WP1 and WP2 together to suggest a refined theory of ASD and I will relate these findings to the symptoms of ASD. Altogether, I aim to contribute to a better understanding of the mechanisms underlying the heterogeneous symptomatology of ASD.

Mots clés : autism spectrum disorders, predictive coding, perception, prior, precision, sensory, learning

Participants :
- KU Leuven (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 178320.0 €
Projet ParaplegiaERDros (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Axonal endoplasmic reticulum (ER) is a poorly characterised compartment that is mainly tubular, smooth, and forms a network for long distances along axons. Many mutations for the motor axon degeneration disease, hereditary spastic paraplegia (HSP), affect proteins that model ER shape. The Fellow will test the model that these proteins help form axonal ER, which is disrupted when these proteins are mutated. The time for this is opportune; the host lab has developed tools to detect impaired axon ER organisation in Drosophila; and new HSP genes, some encoding ER proteins of unknown function, are being identified continuously in human patients. To identify proteins involved in its formation, the Fellow will test ER-localized HSP gene products, both singly and in multiply mutant genotypes, for roles in ER organisation in larval motor axons. She will also test whether similar defects appear in long motor and sensory axons in live adults as they age. Finally she will test the effects of HSP protein loss on the finer structure of ER and its association with mitochondria. Through this work the Fellow will help pioneer characterisation of a poorly understood but important cell compartment: how it is formed and some effects of disrupting it. Along with the broader research and training environment, this will help her to develop a profile for her own work in this area.

Mots clés : drosophila, endoplasmic reticulum, axons, hereditary spastic paraplegia

Participants :
- University of Cambridge (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet InTheMLLrBALL (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

B-cell acute lymphoblastic leukemia (B-ALL) is the commonest cancer in children and B-ALL with mixed-lineage leukemia rearrangements (MLLr) has a particularly dismal prognosis compared with other B-ALLs. Many MLLrB-ALL patients are refractory to chemotherapy and eventually relapse. Thus, MLLrB-ALL remains clinically challenging. Adoptive transfer of T cells engineered to express artificial chimeric antigen (Ag) receptors (CARs) targeting tumor cell surface-specific Ag is an exciting new approach for cancer immunotherapy. Clinical trials in patients with advanced B-ALL treated with CAR-T cells against CD19 have shown impressive disease remission; however relapse still occurs with loss of CD19. Importantly, the B-ALL patients who have not responded to CD19 CAR-T cells were mainly those carrying MLLr. A strategy to offset tumor Ag-loss relapse is to modify T cells with one CAR molecule containing two different binding domains in tandem (bispecific CAR). By using both in vitro and in vivo approaches, I plan to improve CD19 CAR-T cell therapy for MLLrB-ALL by i)developing a novel bispecific CD19/NG2 CAR, which we expect will reduce single-Ag immune pressure, and ii)through the combination of CD19 CAR-T cell therapy with P-D1/PD-L1 blockade. How to achieve a long-term persistence of CAR-T cells in the host still remains a major challenge in adoptive T cell immunotherapy, and therefore understanding the interplay between T cells, MLLrB-ALL blasts and mesenchymal stromal cells/stroma is fundamental to improve the efficiency of this immunotherapy. We will thus address in vitro and in vivo the contribution of the leukemia microenvironment to CAR-T cell efficacy, as a potential tumor microenvironment (PD1/PD1L)-mediated indirect mechanism of immune escape to CAR T-cells. This cutting-edge proposal will increase my scientific potential and I will be benefited with the complementary/leadership training activities already planned to reach in a near future an independent position.

Mots clés : leukemia, immunotherapy, car t cells

Participants :
- Fundación Josep Carreras Contra la Leucemia (Espagne) — Coordinator, beneficiary, Recherche, subvention : 158121.6 €
Projet REPTOL (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

B-cell chronic lymphocytic leukemia (CLL) is a frequent B-cell leukemia of unknown etiology with the strongest familial inheritance among lymphoproliferative disorder. A key finding about CLL cells is that derive from autoreactive B lymphocytes, exhibit stereotyped Abs structures, and poly/auto-reactivity. Our long term goal is to prevent CLL by understanding the biology at the basis of CLL ontogeny. Our hypothesis is that an inherited CLL predisposition causes alterations in pre-leukemic B cells due to compromised immune tolerance, promoting, eventually, transformation event(s) that give rise to CLL. Such alterations skew the IG repertoires leading to enrichment of specific B- cell rearrangements with abnormal Ab reactivity. The overall goal of this study is to understand the role of inherited CLL predisposition in altering the IG structural repertoire and to determine the maturation step(s) and B-cell subset(s) at which these occur. Aim: Define a CLL-related BCR repertoire by analyzing the non-leukemic B-cells from patients with CLL. We will perform high-throughput BCR IG sequencing of non-leukemic B-cells of patients with familial and sporadic CLL. We will identify alterations in patient IGH repertoires compared controls to define a CLL-related repertoire. We expect to define an IGH repertoire difference in CLL patients that will result in the emergence of a mature B-cells with specific rearrangements normally not present. This approach to study CLL in a familial hierarchy diverges significantly from previous studies since it does not try to identify genetic alterations but focuses on structural and functional uniqueness of non-leukemic B-cells, we also avoid the background noise from the alterations specific for the leukemic clone. This study will unveil basic B-cell functional aberrations leading to the development of CLL, and its cellular origin, thereby providing the basis for the development of novel prevention and therapeutic strategies.

Mots clés : immunoglobulin, repertoire, chronic lymphocytic leukemia, deep sequencing

Participants :
- University of Genoa (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 180277.2 €
Projet MCNTMTDC (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

BACKGROUND: Dendritic cells (DC) are professional antigen presenting cells able to provide protective immunity to cancer. DC undergo functional maturation that can lead to tolerogenic phenotype associated with immune-suppression in cancer by a still unknown mechanism. Recently the host laboratory revealed a new role of IKKβ/NF-kB signalling in the tolergenic function of DC. However, the upstream regulators of this signalling and its implication in cancer have not yet been addressed. Since malignant cells consume high amounts of nutrients and DC become tolerogenic in low nutrient conditions possibly under the control of the master energy sensor AMP kinase (AMPK), a pseudo-starvation state in tumour-associated DC (TADC) may be responsible of their tolerogenic activity. AIMS: To determine the metabolic role of AMPK and the potential links with IKKb/NF-kB signalling in the tolerogenic activity of TADC in melanoma context. METHODS: I will use mice with a deletion of IKKβ in DC (IkbkbΔItgax) generated in the host laboratory and will generate mice with a deletion of AMPK in DC (Ampka1ΔItgax). Isolated DC will be cultured in high/low nutrient conditions or in the presence/absence of melanoma cells. Activation of AMPK and IKKβ/NF-kB signalling will be analyzed in these conditions and correlated with DC maturation. TADC will be analyzed in vivo using a mouse melanoma model with conditional melanocyte-specific expression of BRafV600E combined with PTEN deletion. The contribution of IKKβ and AMPK activation in TADC during tumour development will be assessed using (i) a skin graft model from BRafV600E mutant mice to IkbkbΔItgax and Ampka1ΔItgax mice and (ii) chimeric mice generated with bone marrow cells from IkbkbΔItgax and IkbkbΔItgax mice transferred to irradiated BRafV600E mutant mice. EXPECTED RESULTS/IMPACT: To understand the tolerogenic activity of TADC, which will give insight into potential strategies for overcoming tumour-induced tolerance in DC vaccination approaches.

Mots clés : ampk, dendritic cells, ikk, nf kb, immunological tolerance, melanoma, metabolism

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 173076.0 €
Projet BODICON (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

BODICON examines processes of identity negotiations under colonial regimes by investigating the biocultural effects of conquest and colonisation of the Roman Empire. Representing a new generation of contact studies, the aim is to expand upon traditional elite/non-elite dichotomies or the focus on the health of conquered peoples toward how political transformations are incorporated by the human body of both the colonized and the colonizers. The research focuses on Roman Macedonia (Greece) and explores variable effects of colonisation by analyzing skeletal remains and burial patterns from the colony of Dion, the sacred city and pilgrimage site of ancient Macedonians. To achieve this aim, BODICON adopts for the first time a novel, multifaceted and holistic approach that combines bioarchaeology and current, sophisticated theoretical reflection on culture contact and admixture of populations with cutting-edge interdisciplinary techniques and methodological innovations from other scientific fields (paleodietary reconstruction, biodistance analysis, radiochronology). The Fellowship will offer to the Experienced Researcher (ER) the opportunity to acquire advanced intellectual and technical training and new skills in these fields and reach the research objectives. At the same time, the Fellowship is the timely opportunity for the ER to re-establish her career after a prolonged break and the ideal next step in order to re-enforce her research position. Finally, the creation of interdisciplinary networks as well as the dissemination and communication of the results to the scientific community and the broader public will first, contribute to the global understanding of the formation of modern national identities and second, explore the way historical data are used in contemporary political debates.

Mots clés : romanisation, colonisation, contact, mortuary theory, burial customs, social status, necropolis, radiochronology, bioarchaeology, paleopathology, health, diet, biodistance, macedonia, greece

Participants :
- University of Groningen (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187572.48 €
Projet BOLLA (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

BOLLA aims to modulate the bandgap of halide perovskites to obtain versatile solar cells with stable power outputs. The ultimate goal will be coupling such devices with an electrochemical system to engineer an inexpensive, solar driven photo-oxidation water purification system. It will represent a breakthrough in the field of (i) solid-state physics of halide perovskites, shining light on instability mechanisms driven by defects in Sn-containing materials, (ii) photovoltaic, developing stable commercial tunable solar cells, and (iii) water treatment, serving as point-of-use system to obtain safe drinking water free of harmful organic pollutants. The project will start from the design and synthesis of a suitable solution-processed Sn-Pb hybrid perovskite material, whose chemical composition will be tweaked to obtain both narrow and wide bandgap structures with optimal charge transport properties and stability. The fundamental chemistry of defects and the related optoelectronic mechanisms will be investigated as primary source of instability. The engineered material will be integrated in fully-printable, metal-free architectures using only methods compatible with large scale production. Finally, individual wide and narrow bandgap solar cells and series-connected configurations will be combined with an electrochemical system to provide the necessary power to maximize the efficiency in degrading organic pollutants in wastewater. Beyond the main target, the project will proceed through the realization of intermediate and high impact targets, which include advanced photophysical characterization of Sn-Pb hybrid perovskites and fabrication of fully-printable carbon based Sn-Pb devices. This multidisciplinary project will be carried out at the Italian Institute of Technology (Milan) under the supervision of Dr. Petrozza and complemented with Secondments in the Technical Research Centre of Finland VTT (Espoo) and the Helmholtz-Zentrum Berlin HZB (Berlin).

Mots clés : hybrid perovskites, tunable bandgap, spectroscopic techniques, fully printable solar cells, photoelectrochemistry

Participants :
- Italian Institute of Technology (Italie) — Coordinator, beneficiary, Recherche, subvention : 171473.28 €
Projet UNBRACE (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

BRAF mutant (MT) colorectal cancer (CRC) accounts for 10-15% of CRC and represents the subgroup with the worst overall survival. There is an urgent need to identify strategies that hit the 'Achilles Heel' in poor prognostic BRAFMT CRC. Preliminary data from the host lab have shown that BRAFMT CRC cells are vulnerable to disturbances in the Endoplasmic Reticulum (ER)-specific Unfolded Protein Response (UPR) machinery. The overall aim of the proposal is to identify whether the ER stress activator ONC201 in combination with MAPKi (MEK1/2i or BRAFi) will be a novel treatment strategy for BRAFMT CRC. Specific objectives of the proposal are 1. Investigate the effect of ONC201 combined with MAPKi in BRAFMT CRC in vitro. 2. Investigate the in vivo effect of ONC201 with MAPKi using BRAFMT CRC syngeneic and patient derived xenograft models. 3. Assess prognostic/predictive role of ER stress proteins in CRC. UNBRACE will go beyond the current state-of-the-art by (i) developing a novel treatment strategy targeting the biology of poor prognostic BRAFMT CRC; (ii) using relevant pre-clinical models and clinical available datasets to underpin a novel stratified solution for BRAFMT CRC with poor clinical outcome. UNBRACE adopts the concept “personalized medicine strategy” through applying a novel approach targeting BRAFMT CRC. This fellowship will provide the researcher, through mobility, an increased set of excellent skills (e.g. molecular pathology; patient derived xenografts, 3D organoids), which will give him the opportunity to become a future leader in experimental cancer medicine. The fellowship will result in a strong collaborative network between the host and partner institute, transfer of knowledge between academia and industry, ultimately resulting in a phase I clinical trial in BRAFMT CRC. The fellowship can form the basis to attract other scientists internationally, from other disciplines and sectors to receive training in these unique R&I skills.

Mots clés : colorectal cancer, oncogenic braf, unfolded protein response, in vivo models

Participants :
- Cell Stress Discoveries (Irlande) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 187866.0 €