Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet gdTCR-Ligand (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Gamma-delta (gd-)T cells are a fast acting subset of T cells that recognize a wide variety of ligands. In contrast to alpha-beta T cells they are not restricted to classical peptide-MHC antigens. Our preliminary data on a gd-T cell clone shows selective recognition of tumour cells mediated through a novel ligand. The aims of this action are; 1) elucidating the molecular mechanism of the gd-T cell receptor (TCR) recognizing the novel ligand on cancer cells and 2) generating therapeutic agents for cancer cells. A multidisciplinary approach will be used to unveil the interaction of the gd-TCR with its ligand. The gd-TCR and novel ligand molecules will be made using recombinant expression. These proteins will be used to characterize this interaction in detail by determining the affinity and the crystal structure. The results generated in this part of the action will increase the current knowledge regarding gd-T cell ligands. The researcher will reintegrate in his home country using his skills in structural immunology, which he acquired in the Rossjohn laboratory at Monash University in Australia, to address the molecular mechanism of the gd-TCR ligand interaction. Additionally, he will be trained by the host laboratory in in vitro and in vivo immunological assays.


Participants :
- University Medical Center Utrecht (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 177598.8 €
Projet NMRSIGN (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Gas-sensing proteins play an important role in mediating biological events. Soluble guanylate cyclase (sGC) is activated when nitric oxide (NO) binds to heme Fe of sGC, and then stimulates cyclization of guanosine 5-triphosphate (GTP) to the second messenger cyclic guanosine 3,5-monophosphate (cGMP), which in turn has a direct role in the control of a variety of physiological processes in several signal transduction pathways. Disruptions in the NO/sGC/cGMP signalling pathway have been linked to a variety of diseases including congestive heart failure, stroke, hypertension and neurodegeneration. In this proposal, we will derive novel molecular insight into the heme-containing sensor domain of human sGC that is the primary receptor for NO and therefore plays a significant role in NO-signalling by employing structural and computational methods. The project will use the power of solution NMR spectroscopy and enhanced conformational sampling computational approaches to improve our atomistic understanding for this key biological protein and to identify a representative conformational ensemble that will be used in virtual screening of chemical libraries, so as to identify new, original, and more effective compounds for the activation of sGC. This novel approach of combining NMR and computational MD data to identify receptor conformations that play a major role in biomolecular recognition before commencing the structure-based virtual screening is expected to have a major impact in the field of drug design. Throughout this fellowship, the fellow will gain invaluable experience by combining the already accumulated experience in computational biology and CADD with advanced methods using NMR and computational data for the study of biomolecular structure and dynamics. This fellowship is expected to play a pivotal role at his reaching a position of professional maturity and will contribute to his successful transition to an independent research leader.

Mots clés : gas sensing proteins, solution structure and dynamics, molecular dynamics simulations, ligand binding, virtual screening, computational docking

Participants :
- University of Patras (Grèce) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 164653.2 €
Projet GenderQuotas (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Gender quotas are a widespread electoral reform aiming to tackle gender inequality in politics. A rich body of literature focuses on the impact of gender quotas on the articulation of women’s interests in national legislatures. Yet we know very little about the transformatory potential of gender quotas for local decision making. Do gender quotas challenge existing practices of local decision making and advance democratization in clientelistic regimes? This research project investigates the impact of gender quotas on the democratic quality of local decision-making processes in Albania. Do women push for transparency, accountability, and responsiveness? How does women’s engagement in local decision-making processes change over time? The project offers a unique and innovative perspective into the topic of gender quotas and democratization through the combination of theoretical and methodological approaches, original data, interdisciplinary approach, and comprehensive public engagement and dissemination of research findings. The proposal relates with a novel interdisciplinary approach that draws on studies of democratization, representation, political anthropology, and feminist institutionalism. The project will enhance the knowledge and skills of the Experienced Researcher by providing state-of-the-art training in data analysis and management – Python Programming Language and ATLAS.ti – advanced knowledge of theoretical and methodological approaches, and scientific and transferable skills. The knowledge and skills combined with networking and collaboration will place the Experienced Researcher in a competitive position among successful researchers in Europe.

Mots clés : gender quotas, institutional change, democratization, decision making processes

Participants :
- Uppsala University (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 152125.05 €
Projet MoDATS (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Gene expression is the fundamental process that in all cells produces functional protein from a genomic DNA template using a messenger RNA (mRNA) intermediate. Eukaryotic gene expression involves transcription--the polymerization of mRNA--and splicing--the removal of non-coding regions from the mRNA. Recent evidence shows that nascent mRNAs are spliced while still being transcribed, not after completion of transcription, and that splicing machinery regulates transcription. This cross-talk complicates understanding of gene expression, as its mechanism and consequences are not understood. This project proposes using model-based data analysis, applied to multiple types of data, to study the kinetics of coupled transcription and splicing. Model-based data analysis is a statistical framework in which models are formulated as probability distributions encoding the stochastic interactions between components, including observed data. Knowledge of the underlying mechanism--here, biological--is used to quantify both the phenomenon, and the uncertainty resulting from partial knowledge and noisy observations. The need for such analysis is acute in modern biology: decades of molecular biology have yielded detailed information on specific molecules and pathways, and now next-generation sequencing (NGS) allows scientists to collect gigabytes of data on thousands of distinct molecules simultaneously. Yet, integrating these approaches is challenging: biologists struggle to analyze NGS data in ways that give insight into known--and previously unknown--biological mechanisms. Here, the model-based data analysis paradigm will be used to interrogate the interplay of transcription and splicing, using state-of the art data including time-resolved NGS measurements of RNA processing. Working with experimentalists, we will quantify the kinetics of splicing in constitutive genes by labeling nascent transcripts, and estimate the effect of splicing on polymerase elongation genome-wide.


Participants :
- University of Edinburgh (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet DIFFER (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : SIGNED

Genetic diversity – that is, the genomic variation among individuals of a given species – is pivotal for adaptation to environmental alterations and an important factor for ecosystem resilience. Yet, the determinants of genetic diversity remain poorly understood. Population size is often used as a proxy for genetic diversity, but the amount of genetic variation within populations is not always reflected by their population size. Instead, factors such as linked selection, the recombination-, mutation-, and speciation rate, or life history and ecological traits may be more strongly connected to genetic diversity. So far, the interplay of all these parameters has not been empirically investigated, so that their relative contributions to genetic diversity are unknown. In DIFFER!, I propose to thoroughly examine the role of all these potential determinants of genetic diversity by means of combining cutting-edge genomic techniques with a highly suitable model system: the more than 200 endemic cichlid fish species of the East African Lake Tanganyika. Owing to their great morphological and behavioral variation, contrasting speciation rates, and their recent radiation, these fishes offer an ideal framework for comparative analyses. Availability of long-read reference assemblies, recombination maps, a massive dataset of underwater photographs for estimating census population sizes, together with population sequencing of selected species and family-based ‘trio’ sequencing will enable me to investigate specifically the interplay between genetic diversity and (i) life history and ecological traits, (ii) speciation and hybridization rates, and (iii) mutation rates, while at the same time controlling for variation in population size, selection, and recombination. The results of this project will contribute towards the understanding of organismal evolution and provide a new basis for the evaluation of genetic diversity in ecosystem management.

Mots clés : genetic diversity, biodiversity, whole genome sequencing, speciation, hybridization, mutation rate, selection, life history traits, ecosystem resilience

Participants :
- University of Basel (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 304724.16 €
Projet RecInRep (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Genomic instability is the main driving force of tumourigenesis, as highlighted by the cancer predisposition conferred by mutations in caretaker genes. DNA replication stress has recently received much attention, for its causative role in transformation and as a strategy for cancer therapy. Besides other mechanisms protecting replicating chromosomes from genotoxic stress, transient fork remodelling into four-way junctions (fork reversal) is emerging as a key transaction to assist template repair or to tolerate DNA damage and replication interference. Factors and mechanisms modulating this transaction are just beginning to emerge. The central recombinase RAD51 was recently shown to promote fork reversal, uncovering a fork-specific role for homologous recombination (HR) proteins, beyond their established role in the double-strand break repair. However, the molecular determinants controlling RAD51-mediated fork remodelling are yet unknown. I propose to gain mechanistic insight into the role of RAD51 and other HR proteins in replication stress, using an integrated, multidisciplinary approach, which combines my current biochemical expertise with specialized cell biology and single-molecule techniques available in the host lab. In particular, I will first set up a microscopy-based screen to identify factors that regulate RAD51 recruitment at replication forks upon stress. Then, I will use a combination of single-molecule and cell biology techniques to investigate how these novel RAD51 regulators mediate in vivo RAD51 role in fork protection and remodelling. Finally, I will establish an in vitro system to study biochemically the mechanisms by which RAD51 and the novel identified factors catalyse replication fork remodelling. I believe that this "holistic" approach will be instrumental not only to define the molecular basis of cancers with a HR-defective genetic background, but also to provide the groundwork to develop more effective chemotherapeutic strategies.

Mots clés : homologous recombination, genome stability, cancer, high content microscopy based genetic screening, single molecule approaches, replication fork remodelling

Participants :
- University of Zurich (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 175419.6 €
Projet StratifiedGRANULAR (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Geophysical granular flows, like rock avalanches and debris flows, represent a serious hazard to life and infrastructures in Europe. Yet their dynamics is still far from being completely understood. Recent experimental investigations on granular flows showed that velocity and solid volume fraction exhibit a stratified pattern along the flow depth. This indicates the superimposition of different rheological regimes. Moreover, non-local rheological theories have been recently proposed for capturing momentum exchanges, driven by the occurrence of force chains. The present multidisciplinary project aims at developing a computationally cost-effective multi-layer depth-averaged model for describing rheologically stratified granular flows. The model, having much lower computational costs than three-dimensional models, will be designed to capture the essential physics of granular flows in the depth-wise direction. To properly take into account the curvature effects due to basal topography, the model equations will be derived in curvilinear coordinates attached to the topography. Moreover, a suitable non-local constitutive law will be incorporated. The resulting equations will be numerically integrated by a proper finite volume scheme, taking into account their main mathematical properties, i.e. non-strict hyperbolicity and non-conservative form. The model validation will be carried out by using a wide experimental data set, previously gathered by the applicant on dry granular flows. The last stage of the project is devoted to extending the multi-layer approach to cases with dense interstitial fluid, so as to allow its application to debris flows. In line with H2020 priorities, especially as regards sustainable human settlements and their resilience to natural hazards due to climate changes, the project has the potential to provide an advanced mathematical-numerical tool for better identifying the hazardous areas associated with avalanches and debris flows.

Mots clés : granular flows, debris flows, rheology, multi layer depth averaged model, shallow water, non conservative hyperbolic system

Participants :
- Technical University of Darmstadt (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 159460.8 €
Projet PERSEUS (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

Giant molecular clouds (GMCs) are the principal sites of star formation. The derivation of cloud properties are complicated by their large spread in distance along the line of sight. Consequently, to gain insight into the GMCs' physical states one compares parsec-sized clouds of a few hundred solar masses in the solar neighbourhood to the largest, million-solar-mass GMCs in the distant Milky Way. The main goal of my project is to produce the first map of the Perseus Spiral Arm in our outer Galaxy as would be seen by an external observer at fixed spatial resolution. The Perseus Arm extends over one third of the Milky Way's observed span and covers different environmental conditions. HI, 12CO and 13CO data of the Perseus Arm will be convolved to the same spatial resolution and regridded onto maps of constant linear scale. I will extract a fundamental benchmark sample of GMCs using cloud-finding algorithms for comparison with GMCs in the inner Galaxy to study the impact of different kinds of environments. I will reproject the Perseus Arm maps to any desired spatial resolution, to match and compare with observations of nearby galaxies. The phase balance between the atomic and molecular gas, the clump and star formation efficiency will be derived to investigate the relation between spiral arms and star formation. This first common resolution study of the Milky Way's GMCs will be of benefit for the galactic and extragalactic community and allow me to broaden my expertise and skills in the inner Galaxy to a new environment in the outer Galaxy. I will be able to expand my network through collaboration in the field and with colleagues from Exeter. My goal to place the Milky Way in the context of other galaxies with extragalactic collaboration will enable me to become one of the few experts in the field, which will help me to achieve my long-term goal to obtain a permanent academic position.

Mots clés : perseus spiral arm, physical properties of molecular clouds, star formation, atomic and molecular gas, milky way, extragalactic studies, common resolution mapping

Participants :
- University of Exeter (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet MHT-ImmunoEnhancer (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Glioblastoma (GBM) is one of the most lethal and untreatable human tumours, and is characterized by its extremely poor prognosis. Conventional therapies, including surgery, radiotherapy and chemotherapy, have not resulted in major improvements in the survival, due to high recurrence and tumour spreading. Therefore, there is an urgent need to develop new effective therapies to improve patient survival. The establishment of an immunosuppressive tumour microenvironment (TME) in GBM is known to limit the cytotoxic effects of conventional therapies and in this context, myeloid-derived suppressor cells (MDSCs) play a critical role by promoting immune tolerance, tumour growth and spreading. Hyperthermal therapy in GBM has resulted in improved immune reactivity of tumours, despite this, its effectivity has been limited by its inability to overcome the immunosuppressive TME and induce strong systemic antitumour responses. Consequently, targeting MDSCs in combination with thermal ablation therapies appears to be a very promising strategy. The goal of the MHT-ImmunoEnhancer project is the development of a dual stimuli-responsive hybrid polymer/Iron oxide nanocubes (IONCs) delivery system in order to combine local fever-range Magnetic Hyperthermia (MHT) with MDSC depletion-targeted immunotherapy for intratumoral treatment of GBM. The specific objectives of our strategy are, 1) to exploit the superior heating efficiency of the hybrid polymer/IONCs platforms to induce tumour damage. 2) To turn the immunosuppressive TME into an immunosupportive one, by local delivery of CpG oligonucleotide; along with 5-Fluorouracil (5-FU), a chemotherapeutic agent. 3) To release CpG and 5-FU specifically at the tumour site under the appropriate stimulus (pH or enzymes/temperature), thus enhancing their tumour retention and therapeutic effect. All these actions will result in the reduction of T-cell-suppressive activity of MDSCs, enhancement of antitumour immune response and tumour regression.

Mots clés : magnetic hyperthermia, immunotherapy, nanotechnology, glioblastoma, drug delivery

Participants :
- Italian Institute of Technology (Italie) — Coordinator, beneficiary, Recherche, subvention : 183473.28 €
Projet BraINstorm (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Glioblastoma (GBM) remains a non-curable disease due to its high complexity and its position beyond the blood-brain barrier, which precludes access by conventional therapies. The current standard of care includes tumor resection surgery followed by radiotherapy or chemotherapy; an invasive process with a survival rate after five years is less than 5%. Tumor-associated macrophages (TAM) type 2 (M2 macrophages) comprise 30-50% of the infiltrated cells in GBM microenvironment and support tumor expansion. Immunotherapy represents an appealing strategy to treat several cancer types by turning the immune system against tumor cells; tumor antigen peptides (TAAs) recently emerged as an immunotherapeutic approach that can provide for a long-lasting immune response. Immunomodulatory oligonucleotides can “switch” M2 macrophages into M1 macrophages that produce an anti-tumoral effect. The BraINstorm (Brain INtranasal storm) project aims to engineer a hyaluronic acid (HA)-based combination conjugates that tackle GBM by the stimulation of the immune system via the delivery of TAAs and an immunomodulatory oligonucleotide (CpG) that promotes M2 macrophage “re-education” generating an “anticancer storm”. In parallel, taking advantage of the intrinsic muco-adhesivity of HA, BraINstorm will explore the nose-to-brain drug delivery, a more patient-friendly route that reduces the invasiveness. Novel combination immunoconjugates will be fully chemical-physical characterized and preliminary in vitro studies will be performed assessing the biocompatibility, drug release, and nasal mucosa barrier crossing in an ex-vivo model. Finally, the prophylactic and therapeutic activity of the HA-based conjugates will be in vivo explored in a clinically relevant GBM in vivo model through intranasal (IN) and local treatment administration with regards to effects on tumor size, immune memory, and survival.

Mots clés : immunotherapy, nanomedicine, biomaterials, intranasal drug delivery, glioblastoma, tumor associated macrophages

Participants :
- Université Catholique de Louvain (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 166320.0 €