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

Infinite objects are ubiquitous in computer science, e.g., an interactive program may be modelled as taking for input a stream (an infinite list) of requests and producing a stream of responses. In theoretical computer science infinite objects play an important role e.g. in automata theory and exact real number arithmetic. Representing and reasoning about infinite computations is crucial in designing safe software systems. The objective of InfTy is to devise mathematical methods for reasoning about programs manipulating infinite objects, developing compositional typed formalisms and integrating them with infinitary rewriting techniques. Our methods will be compositional and applicable to higher-order programs, while still adopting the operational perspective of rewriting, thus opening up a new viewpoint on higher-order typed formalisms for corecursion. We will extend Pure Type Systems with coinductive types, providing a general yet simple theory for type systems with infinite objects and unifying previous type-based and rewriting-based work on productivity. By establishing infinitary normalisation and infinitary confluence for typable terms, we will construct Böhm models for type systems with corecursion. Recently, a coinductive approach to infinitary rewriting has been proposed by Endrullis et al., and coinductive proofs for some results in infinitary rewriting have been developed by the fellow. The coinductive approach simplifies investigations in infinitary rewriting and thus it is our chosen methodology. This approach, which we will further develop, is by itself of high interest to the rewriting community, but our work will also be relevant to the typed lambda calculus and programming languages communities. The supervisor has strong expertise in rewriting, particularly infinitary rewriting. He developed much of the theory of Infinitary Combinatory Reduction Systems crucial for the present proposal.

Mots clés : term rewriting, infinitary rewriting, lambda calculus, type systems

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 200194.8 €
Projet CD300f (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Inflammation after spinal cord injury (SCI) exerts a key effect on the progress of both degeneration and regeneration after a traumatic injury. In addition, it has become increasingly clear that understanding the interaction between metabolism and immune function can provide an insight into cellular responses to different challenges. Recent reports from our group and others, suggest that metabolic reprogramming and immune receptors play an orchestrated role in modulating microglia and macrophage phenotype. An interesting example is CD300f, a very unique immune receptor that: i) displays a dual activating/inhibitory capacity; ii) is important for the phagocytosis of apoptotic cells and putatively of synapses; and iii) regulates microglia immunometabolic phenotype. Our hypothesis postulates that, by modulating immunometabolism, CD300f plays an important role in neuroprotection under neuroinflammatory conditions. In the current project, we propose to addresses the interplay between inflammation and metabolic reprogramming by evaluating the role of microglia/macrophage CD300f and their metabolic reprogramming after SCI. We will also test the efficacy of a mitochondrial modulator as a novel neuroprotective strategy for the stimulation of microglial mitochondrial oxidative metabolism. This proposal is based on a set of unpublished data produced by both the ER at the Institut Pasteur Montevideo and the host institution. We will use novel tools generated by our group as the CD300floxP mice, that crossed with CX3CR1-Creert mice will enable to the conditional CD300f KO in microglia and barrier macrophages, and compare these results with global KO mice. The results generated will provide novel insights related to the mechanisms underlying SCI, and for the understanding of how the immune system and the metabolism dialogue in SCI. This could have important implications in a broad spectrum of neurological diseases, where inflammation contribute detrimentally to the pathology.

Mots clés : immunometabolism, microglia, macrophages, inflammation, spinal cord injury, immune receptors

Participants :
- Autonomous University of Barcelona (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 172932.48 €
Projet Onco-inflammation (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : TERMINATED

Inflammation is suspected to be the first step leading to cancer due to alcohol consumption or tobacco smoking between others. Little is known of how inflammation triggers genetic changes leading to tumorigenesis. Recently, I show that TGFb, a cytokine present during inflammation, is able to generate aneuploidy, polyploidy and plausible chromosomal rearrangements in breast cells. Such effects were mediated through the induction of the epigenetic reprogramming EMT. In view to understand how inflammatory signaling can affect the genome integrity, I design the project Onco-Inflammation, to study one of the most lethal cancer, the pancreatic ductal adenocarcinoma (PDAC), where therapeutic options are greatly limited. Using several mice models of pancreatitis, we will follow the establishment of genomic insults, and in particular focusing in whole genome doubling, nuclear envelope disruption and micronuclei. I will evaluate the genetic diversity present under pancreatitis and weigh the roles of the epigenetic re-programming Acinar-Dutual-Metaplasia as well as the oncogene KRAS, using high-resolution 3D imaging, as well as single cell CNV analysis (Aim1). I will also study the common pathways activated in newly aneuploid cells, in view to find some specific therapeutic target. (Aim2). Several pathways will be tested in an attempt to block cancer initiation and progression. Results will be tested and validated using human samples (Aim 3). At the Host Institution, I will greatly benefit and learn from the scientific guidance from my supervisor, expert in pancreas biology as well as experts in mitosis, genetic instability and bioinformatics. MSCA-IF will be instrumental to develop this initial hypothesis into deeper biological understanding the inflammation and cell plasticity’s roles on genomic instability and represent a crucial support to transition into an independent academic career.

Mots clés : cancer, inflammation, genomic instability, mice models, pancreas, bioinformatic, copy number variation, cellular plasticity, micronuclei, whole genome doubling, translational medicine

Participants :
- Regional Government of Andalusia (Espagne) — Coordinator, beneficiary, Recherche, subvention : 172932.48 €
Projet MUCO-IMMUN (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Inflammatory Bowel Diseases (IBD) are chronic disorders characterized by persistent ulcerations in the gastrointestinal tract, drastically affecting the patient’s quality of life. Initially regarded as “Western diseases”, they have now become a global problem. Despite IBD being a set of inflammatory diseases, the underlying host immune pathways remain unclear, making it difficult to reliably treat and cure patients. The low-fiber Western diet, and the microbial communities that live in our intestines (the gut “microbiome”), have been proposed as major environmental contributors of the disease - but the mechanisms of their contribution are poorly understood. Among the gut microbiome, the mucobiomes are defined as the microbial communities enzymatically geared to digest the host intestinal mucus layer – our first line of defense against invading pathogens. Their mucolytic activities are regulated by dietary fibers. Thus, we hypothesize that, under a low-fiber diet, the mucobiomes catalyze important disease-promoting immune pathways of IBD. Using an original animal model combining genetic susceptibility, dietary fiber deficiency and different microbiota compositions, we aim at highlighting (1) the role of the mucobiome in IBD pathogenesis, and (2) key immune-pathways regulated by the mucobiome. These objectives are ambitious, yet highly feasible given the expertise of the actors. The proposed work provides a unique dimension to understand the underlying pathogenic mechanisms of a key physiological trait of gut bacteria: host-secreted mucus degradation. The success of this project relies on a close interdisciplinary collaboration that will benefit to develop the researcher's career, the hosting group’s projects, the hosting institute's visibility, and establish innovative diet-based therapies for IBD patients.

Mots clés : gastrointestinal mucus system, dietary fiber, host microbiota interactions, human gut microbiota, inflammatory bowel diseases, mucobiome, synthetic microbiota, diet

Participants :
- Luxembourg Institute of Health (Luxembourg) — Coordinator, beneficiary, Recherche, subvention : 166320.0 €
Projet GutILC3 (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Inflammatory bowel disease (IBD), conferring a dramatically increased risk for development of colorectal cancer (CRC), results from an inappropriate inflammatory response to intestinal microbes in a genetically susceptible host. However, the exact etiology of IBD is unknown. Building up on high impact papers from the host group reporting on the recently discovered innate lymphoid cells (ILCs) as key players in mucosal inflammation, I now aim to unravel the role for ILCs in IBD and CRC. Interestingly, while the IL-22 producing ILC3 seem to be crucial in maintaining intestinal homeostasis, the IL-17 and IFN-gamma-producing ILCs can cause inflammation in a mouse model of colitis and are present in human IBD. Furthermore, ILCs were recently described to be involved in modulating immune responses, by interacting with CD4+ T cells and mononuclear phagocytes in the mouse intestine. I aim to identify critical pathways in the crosstalk of ILC3 with other immune cells in the human intestine. The ultimate purpose is to assess how these interactions affect immune homeostasis and disease progression in IBD and CRC. We will pinpoint crucial interaction molecules and cellular processes that can be used for monitoring current therapies as well as finding new therapy targets for IBD and CRC. This truly translational proposal utilizes, in an optimal manner, unique state-of-the-art techniques and patient materials to provide novel insights into the etiology of IBD and CRC. The excellent track record of the hosting group, the highly suitable infrastructure provided by the host institution and my own extensive research experience ensures a high degree of feasibility. Furthermore, this project provides excellent training opportunities, skill advancement possibilities and career prospects for me and its results are expected to have a direct impact on the European society.

Mots clés : innate lymphoid cells, intestinal homeostasis, intestinal inflammation, interaction molecules

Participants :
- Karolinska Institutet (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 173857.2 €
Projet Influenza RNP (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Influenza is a major public health burden, with seasonal outbreaks contributing significantly to mortality worldwide, and the emergence of pandemic strains remaining an ever-present threat. Influenza drug and vaccine conception efforts are aided by a thorough understanding of its molecular biology. A key aspect of the influenza lifecycle is the production of capped and poly-adenylated messenger RNA by the heterotrimeric influenza polymerase (FluPol). Ground-breaking work performed by the Cusack lab, has described with residue-resolution detail, the FluPol structures that form during transcription of short, non-nucleoprotein (NP) bound viral RNAs (vRNAs). However, influenza transcription in vivo occurs within the ribonucleoprotein (RNP) particle and does not utilise naked genome segments. The viral RNP (vRNP) is a super-helical complex composed FluPol bound at the conserved 3′ and 5′ ends of a vRNA, which is coated with NP. The current low-resolution structures provide little information about the molecular details of vRNP function, particularly, how NPs interact with FluPol and the vRNA template. Via an inter-disciplinary approach, I will utilise cryo-electron microscopy methods, transcription assays and single-molecule fluorescence, to obtain the first high resolution structure of a dynamic influenza vRNP, with a particular focus on the spatial organisation of NPs relative to FluPol. In addition to this work facilitating future influenza drug research, it will provide a basis to investigate the vRNP during other lifecycle stages and act as proof-of-principle for study of other viral protein-RNA complexes, such as those from corona-, arena- and bunyaviruses. Work will be performed in the groups of Stephen Cusack and Olivier Duss based at EMBL Grenoble and Heidelberg, respectively. Here, I will have access to world-leading facilities and training opportunities, supporting my growth as an independent researcher and an expert in RNA virus structural biology.

Mots clés : transcription, ribonucleoprotein, influenza virus, cryo electron microscopy, single molecule fluorescence

Participants :
- European Molecular Biology Laboratory (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 184707.84 €
Projet VisHipMem (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Information processing in the human brain depends on the exact timing of neuronal activity. Duty cycles, defining favorable states of activity within the phase of a neuronal oscillation, have been shown to coordinate information processing in the visual domain (Jensen & Mazaheri, 2010) and the formation of new memories (Buzsaki, 2010). While there is little doubt about the interaction between these two domains, the underlying mechanisms are as of yet unclear. The aim of the present proposal is to understand the mechanisms supporting human memory formation by investigating the joint inter-regional coordination of visual and memory-related brain regions. Recent evidence suggests that saccadic eye movements modulate hippocampal oscillations in non-human primates during memory formation (Jutras et al., 2013) and also influence the phase of visual oscillations (Ito et al., 2011; 2013). It is hypothesized that the coordination of these brain areas during information transfer can be unraveled by incorporating saccadic eye movements adjusting the phase of visual and hippocampal oscillations. In particular, it is hypothesized that neuronal oscillations following saccades are instrumental to synchronize visual cortex and hippocampus activity such that visual information is successfully encoded. Oscillatory synchronization in the 5-12 Hz theta/alpha band is expected to establish the ‘functional connectivity’ between the visuo-hippocampal regions, whereas gamma band activity (30-100 Hz), phase-locked to the theta/alpha oscillations reflects the actual information transfer (Lisman & Jensen, 2013; Jensen et al., 2014). The aim of this research plan is to test these hypotheses directly by using a combination of neuromagnetic (MEG), neuroimaging (fMRI) and behavioral (eye tracker) recordings in a memory paradigm.

Mots clés : fmri, human memory, saccades

Participants :
- Radboud University Nijmegen (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 165598.8 €
Projet immunoassays (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Infusion reactions (IRs) are complex, immune-mediated side effects, also known as hypersensitivity reactions (HSRs), that can occur upon intravenous infusion of pharmaceuticals, leading to severe and sometimes life-threatening conditions in patients. Those reactions may arise from a real allergy which is immune globulin class E (IgE) mediated or a “pseudoallergy”. The latter involves no IgEs and may arise because of activation of the complement (C) system called C activation-related pseudoallergy (CARPA). The complement (C-) system is part of the immune system called the innate immune system that is not adaptable and responds to foreign challenges in a non-specific manner. When stimulated proteases of the complement system cleave other C proteins and initiate an amplifying cascade of further cleavages. The end-result of this activation cascade is a massive acute inflammatory response caused by the release of cytokines, anaphylatoxins and the cell-killing membrane attack complex (MAC). Products triggering severe adverse events can include both traditional small molecules but also biologics such as therapeutic antibodies (Abs), fusion proteins, etc. and novel formulations using liposomes or nanotechnology. Regulatory guidance on the assessment of C-mediated infusion hypersensitivity has been published recently for the case of generic liposome production. Hemocompatibility (blood safety) testing for medical devices is requested by EMA and FDA since many years. However, regarding the potential of new pharmaceuticals causing allergies and/or CARPA remains a significant challenge for the industry during nonclinical development as no established safety biomarker nor meaningful, validated animal models are available up to date. During the project “IMMUNOASSAYS” Dr Fülöp proposes the development and quantitative evaluation of three promising specific safety biomarkers via ELISA technology.

Mots clés : in vitro testing, trials

Participants :
- Tecodevelopment gmbh (Allemagne) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 174806.4 €
Projet CellMechSensE (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

Inside tissues, living cells can adhere to a heterogeneous fiber network, the extracellular matrix (ECM). Cells adjust their behavior in response to the local resistance they sense from pulling the neighboring fibers (mechanosensing). As they probe the network and respond to signals, cells can strongly distort the ECM and these deformations can serve as cues for other cells. The cell-generated forces can be large enough to trigger non-linear elastic effects and irreversible transformations of the ECM, resulting in drastic network remodeling. Yet, most theoretical studies have focused on small-force mechanical signals transmitted by an idealized static network. Therefore, the overall research aim of this proposal is to establish a theoretical framework to obtain fundamental understanding on how cells can exploit the non-linearities to extract accurate information by mechanically probing their surroundings. Recent advances in high-resolution, cell-scale imaging and measurement techniques now make it possible to calibrate quantitatively the model from experimental data and high computational power will permit a complete quantitative numerical study of the biological system. This project will bring understanding that will fill a crucial gap of knowledge on the mechanisms controlling individual and collective cell behavior, ultimately allowing key advances on our understanding of body functioning. This comprehension will have a major impact in guiding the design of biological implants and potentially avoid dramatic diseases. With this fellowship, I will extend my research area to biophysics and perform extensive computational simulations under the supervision of Prof. Broedersz. Conducting this research project will raise my academic profile as an expert in mechanical modeling of disordered networks. It will hence increase my chances to achieve my goal of becoming an independent research group leader in statistical modeling of disordered systems in France.

Mots clés : mechanical heterogeneity, nonlinear deformations, plasticity, active network, mechanosensing

Participants :
- Ludwig-Maximilians-Universität München (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 174806.4 €
Projet CAP-SAliPharm (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Insight market requirements are leading the R&D at food technology area to provide ready-to-eat products, microbiologically safe, with organoleptic and nutritional added value, and as longest as possible shelf-life guided by international trade search of competitiveness. Powders are worldwide distributed commodities. Valuable properties associated to them are: stability; easy storage and transportation; nutritional compounds integrated in formulas; price; and limited microbial proliferation. In spite of these characteristics, nowadays the sterilization of powders is not completely solved. Spore-forming bacteria are widely capable to survive in powders during long periods of time, initiating after the rehydration process, a rapid germination and proliferative activity with fatal consequences mainly in infant and elderly. The present project aims to analyse the Cold Atmospheric Plasma (CAP) technology application integrating the study of process parameters and reference powders characteristics to optimize the sterilization process of alimentary and pharmaceutical products. Moreover, the optimized conditions will be validated in real matrices, infant powder (milk formula and cereals) and multivitamin and protein complexes. Finally, the optimized conditions at pre-industrial level will be delivered in technical sheets regarding the technological, microbiological and risk-assessment relevant outputs of the project, contributing to provide the methodological basis for the industrial establishment of more sustainable production of a new generation of powdered products. Such system for powders sterilization has not been described previously and is one of the most ambitious points of research in the present MSCA framework. The present project aims to contribute to the cutting-edge of this technology application at International level, making a significant impact on the position of the European Union in the know-how regarding CAP application.

Mots clés : powders, sterilization, cold atmospheric plasma, non thermal technology, risk assessment, nutritional compounds

Participants :
- University of Applied Sciences and Arts Western Switzerland (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187419.6 €