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

According to the standard model of cosmology, we are witnesses of an epic battle: While dark energy leads to an accelerated expansion, matter and particularly the dark matter, opposes this trend, leading to the observed large-scale structure of the Universe. Since the pioneering discovery of dark energy that lead to a Nobel Prize in Physics, the nature of dark matter is still shrouded in mystery. What we know is that matter can be described as a fluid on macrophysical scales, and that the fluid has, at early times, no overlapping matter trajectories. Yet, matter trajectories do eventually begin to intersect ("shell-crossing"), which marks the starting point of very complex computations in the phase-space on the one side, and the birth of our cluttered Universe on the other side. Understanding the collapse and shell-crossing is quite a challenge that is usually tackled by utterly opposing means, either by (approximative) analytical models or by cosmological N-body simulations. With this Marie-Curie fellowship, I will close this gap and get full control of the instant of shell-crossing in two complementary ways. I will develop full-fledged numerical simulations of the cosmological fluid equations and develop certain matter collapse models, that, at their heart, determine the matter trajectories by exact analytical descriptions until the instance of shell-crossing, where infinities become real and the solutions "blow up". Detecting blow-ups is one of the most challenging and rewarding problems in mathematical physics; by resolving them, precious information will be gained which we will use to improve (heavily used) N-body simulations at the critical vicinity of shell-crossing. The department Lagrange (host institute) is a unique place in Europe that houses both world experts in numerical cosmology and in mathematical analysis, thereby complementing exactly my expertise (exact analytical models). This allows us to solve outstanding problems in interdisciplinary fields.

Mots clés : large scale structure of the universe, shell crossing, cosmological n body simulations

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

Accurate diagnosis of (pre)malignant gastrointestinal (GI)-tract lesions is critical for patient survival. Early detection of asymptomatic disease of the GItract improves the chance of curative intervention by 50−80% as compared to poor five-year survival rates for symptomatic advanced malignant disease. Regular endoscopic surveillance in high-risk patients misses 25% of (pre)malignant lesions – the most clinically relevant marker for malignant progression. This clinically significant miss rate is due to the subtle appearance of such lesions under white-light endoscopy and sampling errors inherent to a random-biopsy surveillance paradigm, which increases inter-operator variability and compromises diagnostic accuracy. Even when malignant disease is detected, lack of sensitive contrast agents compromises delineation of the true extent of the lesion. These factors decrease the physician’s ability to achieve successful therapeutic intervention through resection or ablation. About 33% of GI-tract lesions progress or recur at or near the therapeutic site, commonly requiring aggressive yet often non-curative, systemic treatments negatively impacting the patients’ quality of life. There is an unmet clinical need for endoscopic optical imaging approaches that reliably detect those lesions with high sensitivity and specificity. To develop a clinically viable strategy, I propose to use biodegradable, fluorescent silica nanoprobes (FSN) that provide real-time visualization of the lesions over a range of scales during routine endoscopy. Since FSNs accumulate at the tumor sites solely due to their size and increased vascular permeability, no active targeting is needed, making these imaging agents ubiquitously applicable. Endoscopy augmented with FSNs has tremendous potential for better outcomes particularly in high-risk patients by accurately diagnosing and directing treatment specifically to early lesions at a time when patients are amenable to curative therapeutic intervention.

Mots clés : early detection, optical, nanoparticle, pre malignant, gi tract

Participants :
- Percuros (Netherlands) (Pays-Bas) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 187572.48 €
Projet HippAchoMod (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Acetylcholine released by cholinergic neurons in the basal forebrain is a critical component of the modulatory cocktail governing the emergence, stabilization and reorganization of cortical ensembles of co-active neurons representing the environment. In the hippocampus, ACh renders the state of the network optimal for the acquisition of novel information. Deterioration of cholinergic modulation leads to severe deficits in hippocampal function manifested as debilitating cognitive impairments. Despite decades of intense research fundamental questions are still open about the cholinergic modulation of hippocampal information processing: i) how is the behaviour-dependent firing of different neuron types determined by ACh? ii) how does ACh contribute to the emergence of the spatially selective firing of principal cells, their amalgamation into sequences representing the surroundings of the animal and the storage of “relevant” sequences? iii) how does ACh alter the place code in response to salient environmental stimuli? Technological breakthroughs of the past years have opened the possibilities of addressing these long-standing questions about cholinergic modulation. Thus, I aim to combine the latest electrophysiological recording, optogenetic manipulation and behavioural tracking methods to monitor hippocampal neuronal ensembles in freely behaving mice while manipulating the cholinergic input of the hippocampus by light-responsive microbial opsins. Results of the proposed research programme will decipher the role of ACh in hippocampal information processing and inform us how subcortical modulation contributes to the conversion of external inputs from the environment to internal representations. By accomplishing the programme outlined in the proposal I will be acquainted with the cutting edge technologies as well as skills indispensable for starting my independent research group and expanding the research potential of my home institute.

Mots clés : neurogrid, silicone probes, optogenetics, subcortical modulation

Participants :
- New York University (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Hungarian Academy of Sciences (Hongrie) — Coordinator, beneficiary, Recherche, subvention : 245250.0 €
Projet KAFKA (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Active Flow Control (AFC) mechanisms have tremendous potential in improving flow characteristics in a wide variety of sectors. For effective AFC design, it is essential to determine the sensitivity of each of the control parameters to the flow property of interest. Adjoint methods provide the sensitivity of the objective function to any number of input parameters at a reasonable additional cost. They are based on simple RANS turbulence modelling, which captures poorly the physics of flow especially in the presence of complex flow features such as flow separation, which can be effectively eliminated by flow control. Recently developed Reynolds Stress Models (RSM) display significant improvement in the flow prediction capacity as compared to conventional RANS models, yet adjoints with RSM are not yet available. An alternative for accurate flow prediction is Large Eddy Simulation (LES). Unfortunately resolving the chaotic turbulent motion results in exponential growth of the gradients. Our first objective is to develop an effective discrete adjoint method with an accurate and stable RSM, and compute sensitivities in complex flows involving active control mechanism applied to realistic wing geometries. Although RSM outperforms conventional turbulence models in a host of applications, there is a need for further physics-based calibration for specific flows. Our second objective is to use the adjoint method to drive the model coefficients to their optimum value such that the model results match with high-fidelity simulation data yielding a better turbulence model, which can be applied for effective flow control design in bluff body with severe rear flow separation. Our third objective will be to develop adjoint approaches for chaotic LES flows using the hosting groups' innovative gappy checkpointing approach that retains the accuracy of the LES but regularises the chaotic motion for the reverse adjoint pass, hence avoiding the exponential blowup of the sensitivities.

Mots clés : active flow control, adjoint optimisation, rans modelling, large eddy simulations

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €
Projet DNAmethAML (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Acute myeloid leukaemia (AML) is an aggressive type of blood cancer characterized by uncontrollable growth of immature myeloid cells. Somatic mutations in diverse transcriptional regulators result in aberrant epigenetic landscape in leukemic cells, including patterns of DNA methylation. Due to its reversible nature, this epigenetic mark has been a promising therapeutic target and DNA methyltransferase inhibitors are already being used with varying degrees of success in clinic. The targeted improvement of existing therapies requires a better understanding of mechanisms how altered DNA methylation promotes malignancies. TET2, an enzyme catalysing DNA demethylation, is one of the most frequently mutated epigenetic regulators in AML. Its loss leads to hypermethylation at distal regulatory regions (or enhancers) and increased stem cell self-renewal and leukaemogenesis in the haematopoietic system. In the proposed work I plan to investigate the link between aberrant hypermethylation at enhancers and its role in developing and maintaining AML. Firstly, I will take advantage of clinically relevant AML mouse models that combine TET2 deficiency with AML-specific alterations and annotate DNA methylation-sensitive enhancers using high-throughput sequencing methods (MethylC-seq, ATAC-seq and ChIP-seq). Secondly, I will perform a positive-selection CRISPR-based high-throughput enhancer screen to identify DNA methylation-sensitive enhancers that inhibit leukemic stem cell self-renewal (i.e. tumour suppressive regulatory regions). Finally, I will identify and study the function of transcription factors which binding is lost due to aberrant DNA hypermethylation at these sites. The proposed work will be both discovery-based (genome-wide level) as well as mechanistic.

Mots clés : leukaemia, dna methylation, tet2, mouse models, crispr, cas9, transcription, enhancers

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 200194.8 €
Projet SEXOGENIRI (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Acute myocardial infarction (MI) accounts for millions of morbidity and mortality cases worldwide. While the underlying pathophysiology of cardiomyocyte dysfunction and death during MI-related ischaemia/reperfusion injury (IRI), which occurs due to the restoration of coronary blood flow after MI, is well established, the relevance of sex-based differences in this context is poorly understood. In this action, we aim at understanding the effect of biological sex in the induction of a novel form of cell death in the setting of IRI. The project will examine both mouse and human hearts and will benefit from a range of techniques including, but not limited to in vivo surgery, in vitro cell line evaluation, state-of-the-art microscopy, mitochondrial respirometry and molecular biology methods. The content of the action will enable the researcher to restart his career and gain important academic, interpersonal and laboratory skills. It will also provide an opportunity for the researcher to publish in major journals and disseminate his findings to scientists and the public, which will ultimately help him establish himself in the field of cardiovascular science. The action also helps raise the research and academic profile of the host team and institution and contribute to the development of strong intra-European science networking. Overall, this action aims at contributing to the scientific progress of the researcher and pave the way for the identification of novel therapeutic targets for IRI with direct translational potential.

Mots clés : cardiac, cell death, mitochondria

Participants :
- University of Iceland (Islande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 294359.04 €
Projet ParAdapt (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Adaptation is a key evolutionary process, allowing organisms to thrive in different environments. Studying adaptation is important for understanding biodiversity, and for addressing pressing issues in conservation and medicine. A crucial question is whether adaptive evolution is repeatable and therefore predictable. Patterns in nature suggest that this may be the case: within many species, similar adaptive phenotypes have evolved repeatedly in multiple geographical locations (“parallel evolution”). However, it is often unclear whether the genomic basis underlying parallel phenotypes is the same across locations (e.g. due to mutations in the same gene, or gene flow between locations). With high-throughput DNA sequencing technologies, it is now possible to address this question in unprecedented detail. However, we are lacking a theoretical framework predicting the genomic basis of parallel evolution, as well as powerful analyses of empirical data. Therefore, here I propose an interdisciplinary approach with the following aims: 1. Using computer simulations to study the effects of demographic history and polygeny on the genomic basis of parallel evolution. This will, for the first time, enable quantitative predictions. 2. Generalising the model outlined in 1. by describing it mathematically. 3. Exploring the genomic basis of parallel evolution in an ideally suited organism. I will identify the most powerful analytical methods, and apply these to generate one of the most comprehensive empirical studies so far. This project will be of use to other researchers conceptually, for making system-specific predictions, and by providing widely applicable workflows. It will facilitate new collaborations between my host group (focusing on mathematical analyses of evolutionary processes) and empirical scientists. In addition, it will complement my existing skills in empirical genomics with a new set of analytical and mathematical skills, opening up the best career possibilities.

Mots clés : evolutionary modeling, evolutionary simulations, adaptation, speciation, parallel evolution

Participants :
- Institute of Science and Technology Austria (Autriche) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 166156.8 €
Projet EMERALD (Horizon 2020, appel à projets 2020)
Action : Cofund Doctoral programme
Statut du projet : SIGNED

Addressing the increased need for innovative solutions in medicine and healthcare, as we are witnessing during the current worldwide pandemic, requires more than ever the rise of the unique professional profile of physician-scientists, combining cutting-edge research and technology with medicine. There are several MDPhD programmes in European countries and institutions, but there is none Europe-wide. The EMERALD International Doctoral Programme aims to nurture excellent physician-scientists to advance research, personalised medicine and health care in Europe. Following fair, merit-based, and inclusive recruitment, the programme will hire 24 medical doctors to carry out a PhD in cutting-edge research in seven European centres of excellence in life sciences and biomedicine. The EMERALD fellows will experience mobility across laboratories, sectors and countries, and they will benefit from international, stimulating and creative environments, advanced training, career development and mentoring programmes, and access to high-end technologies and facilities. Importantly, they will benefit from the advanced training on the latest technologies, digital skills, open science and innovation, and from the mentoring provided by the EMERALD programme, with the opportunity to build valuable international networks with different actors in academia, hospitals, industry, patients´ organisations and NGOs. EMERALD counts on the impressive support and collaboration of 37 partner organisations from 10 European countries. The trained physician-scientists will be equipped with skills and knowledge to tackle relevant clinical and research questions, bridging the gap between laboratory research and caring of patients, and ultimately pursuing new approaches to diagnose and treat human diseases.

Mots clés : physician scientists, life sciences, biomedicine, cutting edge technology, digital skills, career development, international, interdisciplinary and inter sector mobility, personalised medicine

Participants :
- Centre for Genomic Regulation (Espagne) — Coordinator, beneficiary, Recherche, subvention : 2278080.0 €
Projet QS21-Mech (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Adjuvants are vital components of modern molecular vaccines that increase the low immunogenicity of subunit peptide and/ or polysaccharide antigens and potentiate the immune response. Despite their key role, the mechanisms of action of many adjuvants, including the clinically-relevant saponin QS-21, are poorly understood, which hampers the rational design of new, improved vaccine adjuvants. To address this gap and shed light into this fundamental biological mystery, the main goal of this proposal (QS21-Mech) is to develop new chemical probes to investigate the molecular mechanism of saponin adjuvants, one of the most potent and promising class of adjuvants. Using a multidisciplinary approach at the chemistry-biology interface, synthetic saponin-based photoaffinity probes will be chemically synthesized, followed by immunological evaluation for adjuvant activity in mice. The active saponin probes will then be utilized in biological/mechanistic studies to discover the putative molecular receptor of these adjuvants using a chemical proteomics approach. The photoreactive group will be used to cross-link the saponin molecule to the putative interacting partner, while the reporter group will serve as a tag for affinity-purification of the cross-linked adducts. Finally, the identity of the putative receptor will be resolved using MS-based proteomics analysis. The identification of the molecular target of the saponin adjuvants will provide unprecedented mechanistic understanding, facilitating the elucidation of their molecular mechanisms of action, which is of fundamental interest in immunology. This knowledge will enable the rational development of improved saponin adjuvants and optimal adjuvant-antigen combinations for vaccines against a broad range of diseases.

Mots clés : chemical immunology, saponin vaccine adjuvants, chemical proteomics, photoaffinity probes, photo crosslinking

Participants :
- CIC bioGUNE (Espagne) — Coordinator, beneficiary, Recherche, subvention : 172932.48 €
Projet Exh-Res-CART (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Adoptive transfer of T-cells collected from patient’s blood and engineered to express chimeric antigen receptors (CARs) has produced unprecedented clinical responses in patients with cancer. CAR-T cells targeting CD19 were recently approved by the US food and drug administration (FDA) and the European Commission (EC) for the treatment of leukemia and lymphoma, heralding a new era for cancer treatment. However, despite the stunning results of CAR-T cells in patients with hematologic malignancies, results with CAR-T cells in patients with solid tumors are far from expected. Although CAR-T cells are able to infiltrate solid tumors and exert antigen directed activity, observed responses in patients with solid tumors have been minor and transient. But what are the mechanisms behind the poor T-cell activity in solid tumors? Are CAR-T cells susceptible to dysfunction in a similar way as the endogenous tumor-specific T cells that fail to eliminate the tumors in treatment-naïve cancer patients? My central hypothesis is that CAR-T cells become exhausted in the tumor microenvironment mainly due to continuous antigen encounter, and that this process can be prevented or delayed. My general aim for this project is to enhance the persistence and function of CAR-T cells by overcoming T-cell dysfunction while promoting T-cell stemness. By using animal models and a combination of innovative technologies, including next-generation sequencing and genome editing I will: 1) elucidate the T-cell intrinsic mechanisms by which CAR-T cells become unresponsive to solid tumors, 2) design new approaches to enable infused T cells to overcome dysfunction and persist within the tumor microenvironment.

Mots clés : chimeric antigen receptors, solid tumors, t cell dysfunction

Participants :
- Fundació Clínic per a la Recerca Biomèdica (Espagne) — Coordinator, beneficiary, Recherche, subvention : 160932.48 €