Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet PlastHealth (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : SIGNED

Microplastic debris pollution (MP), as a serious environmental problem worldwide, is responsible for most of the hidden marine plastic pollution, being found in organisms from algae to top predators. This innovative proposal (acronym: PlastHealth) will provide a comprehensive understanding of the transfer and effect of MP pollution, for the first time, at the ecosystem level with two main objectives: 1) assess the transfer of MPs within the three ecosystem levels, evaluating the effects of MP exposure on the health (such as the gut content, gut damage, metabolic activity and oxidative stress) using biochemical and histopathological analyses; and recovery rate of the model species using fluorescent stereomicroscopy; and 2) investigate the effects of MPs on the gut microbiome of the model species and the subsequent changes in the community dynamics of the plastisphere (microbial community formed on plastic debris) after MPs digestion by the model species using metagenomics. Going well beyond the state of the art in several fronts, a unique experimental setup that includes three functional groups mesocosm model system – a prey (arthropod Artemia salina), a predator (fish Sparus aurata), and a filter feeder (mussel Mytilus sp.). Following a highly interdisciplinary approach, and using advanced techniques, the research plan will test three MP concentrations (0, 10 and 1000 mL-1) and two MP diameters (2 and 10 μm). The strong interdisciplinary and international character of the proposal will greatly contribute to development of new skills and to the expansion of the applicant’s research network. Grounded on an effective communication strategy and with potential to deliver outputs with outstanding scientific, societal, and policy-making impact (health and safety; and environmental) with far-reaching implications well-beyond its focal species and systems, the project will unveil new aspects of MP pollution on marine ecosystems, raising awareness of MP pollution.

Mots clés : marine pollution, ecotoxicology, gut microbiome, life cycle characteristics, recovery rate

Participants :
- Université nouvelle de Lisbonne (Portugal) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 156778.56 €
- Fondation pour la recherche scientifique et industrielle (Norvège) — Partner, associated partner, Recherche, subvention : 0.0 €
Projet O2CELLS (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Tissue engineering (TE) is a multi-disciplinary field that allows the fabrication of hybrid constructs to repair, replace, or induce tissue regeneration. Cells encapsulated in 3D scaffolds have been widely employed; however, encapsulation limits the homogeneous perfusion of vital soluble factors and oxygen. This results from the failure to stabilize a vascularised network within the scaffold and can lead to reduced cell proliferation, gene expression, and extracellular matrix (ECM) deposition. With this, O2CELLS aims to develop cutting-edge advanced devices by employing an integrative strategy with natural-based biomaterials that combine with self-oxygenating microalgae and tissue progenitor cells in original multiscale structural arrangements that will stimulate the regeneration of high-quality vascularised microtissues. For this, perinatal tissues will provide human structural proteins and stem cells with unique features that will be used for the fabrication of bioinks enriched with liquefied microcapsules (“Pockets”) containing the microalgae and mesenchymal cells, and endothelial cells (HUVECs). These biomaterials hierarchical features and angiogenic and osteogenic potential will be fully characterized in vitro and in vivo. O2CELLS will combine a diversity of individually pioneering concepts that could be used in the bioengineering of distinct human tissues, both for therapies and for disease model development. This ground-breaking concept is expected to pave the way to solve one of the significant challenges faced by in vitro bioengineered constructs and devise a broad disruptive platform for tissue engineering or other biotechnology challenges. The technology developed on O2CELLS has the potential to be exceptionally rewarding to the scientific and medical communities which are in line with Goal 3 of UN 2030 Agenda (healthy life and well-being for everyone of all ages).

Mots clés : tissue regeneration, hybrid constructs, human proteins, hydrogels, 3d bioprinting

Participants :
- Université d'Aveiro (Portugal) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 156778.56 €
Projet QuiescentFactory (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The proposed project aims to solve a major challenge in metabolic engineering. In microbial metabolic engineering platforms, consumed nutrients are primarily invested into population growth instead of the production of chemicals of interest. Our team is studying a temperature-sensitive mutant of fission yeast (Schizosaccharomyces pombe), which grows normally at 26°C, but enters quiescence at 36°C, while at the same time maintaining its metabolic activity. Such an engineering platform could represent the holy grail of the metabolic engineering field - a chassis strain that can stop growing but keeps producing metabolites. Application of such pseudo-quiescent strain would be useful to both industrial and academic players. To develop this mutant into a new metabolic engineering chassis, I will first design a molecular cloning toolkit to perform metabolic engineering in S. pombe, which will enable construction and expression of complex biosynthetic pathways. Second, I will characterize the phenotype of the pseudoquiescent S. pombe mutant using a multi-omics approach. I will generate knowledge about mRNA, protein, metabolite and flux dynamics to delineate a genome-scale metabolic model of the chassis under pseudo-quiescence. Then, I will assess the ability of the S. pombe mutant to overproduce 3 different high-value compounds (kavain via phenylalanine, theophylline via purine and artemisinin precursor via mevalonate). Finally, I intend to reproduce the pseudo-quiescent mutant phenotype in other commonly used yeast species (Saccharomyces cerevisiae and Yarrowia lipolytica). In the short term, this research will deliver a new type of a metabolic engineering chassis for the production of complex chemicals to the metabolic engineering community. In the long term, it will contribute to the development of metabolic engineering as a competitive alternative of total synthesis of chemicals, leading to greener and renewable chemical industry.

Mots clés : target of rapamycin, schizosaccharomyces pombe, metabolic engineering, heterologous expression, natural products

Participants :
- Institut national des sciences appliquées de Toulouse (France) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Institute of Organic Chemistry and Biochemistry (Rép. Tchèque) — Coordinator, beneficiary, Recherche, subvention : 166278.72 €
Projet FARAON (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

Historically, one of the biggest challenges in synthetic organic chemistry has always been to synthesize fluoroarenes (Ar-F) and fluoroheteroarenes (Het-F) from cheap, readily available starting materials, as fluorination has always concerned synthetic chemists due to either undesirable safety of reagents, low selectivities or poor reactivities. Since fluoroaryl- (Ar-F) and fluoroheteroaryl- (Het-F) are the most common fluorinated motives among pharmaceuticals development of a completely novel synthetic strategy would be of great importance to the research community. De novo construction of fluorobenzene using C1F1 synthons is an unprecedented process. We foresee that little explored monofluorinated ortoformates (RO)3CF (FOFs) could be a synthetic equivalent to access C1F1 synthon for annulation reactions.

Mots clés : fluoro ortoformates ro 3cf fofs , de novo synthesis, c1f1 synthon, fluoroarenes, fluoro hetero arenes, annulation reaction

Participants :
- Latvian Academy of Sciences (Lettonie) — Coordinator, beneficiary, Recherche, subvention : 162499.2 €
Projet StickyFT (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

EU Mission for Adaptation to Climate Change perceives the improved dryland agriculture as one of the ways to adapt and survive. Humans have the technology and processes to address the major agricultural issues today, such as pest infestation, droughts, the misuse of herbicides; however, the global warming requires a new set of tools and the willingness to adapt from all of us. The key developmental switch for the flower/fruit bearing plants is the change from vegetative to reproductive growth, and the timing is crucial. The climate changes have been already impacting the flowering, as several perennial and annual crops have flowered earlier by about 2 days per decade, during the last 50 years. The flowering locus T is a plant protein highly recognized as a part of the florigen complex, a mobile protein that is produced in the leaf companion cells and transported to the plant shoot apex to induce flowering. My previous work was focused on the FT preference to bind to phosphatidylglycerol (PG), over other lipid species, in the temperature-dependent manner, and the impact on the flowering time. The MSCA Project will address the relevance of the wider array of FT-PG interactions, by utilizing the genetic modifications to produce and characterize the FT mutant proteins with enhanced lipid-binding properties. The super sticky FT would be difficult to remove from the membrane, which could have a potential industrial application. A challenge would be to create the protein that could not bind to the membrane, which will shed a new light onto flowering regulation. The multidisciplinary approach, consisting of molecular biology, biochemistry, structural chemistry, and biophysics, will produce deliverables for the subsequent in planta project. The measured impact of different ambient temperatures will provide us with the knowledge of the fine-tuning and control over the protein-lipid interactions, which could have the long-standing effects in the agricultural applications.

Mots clés : protein lipid interaction liposome system ambient temperature recombinant proteins genetic modification

Participants :
- Institut de Chimie (Slovénie) — Coordinator, beneficiary, Recherche, subvention : 171399.36 €
Projet PHAGE (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Phages have the potential to be used in therapy because they can infect and kill pathogenic bacteria, including those resistant to antibiotics. Although phages are simple, details of their life cycle remain unknown. To start the infection, phages bind to and eject their genome into bacteria. During adsorption, the phage baseplate recognises receptors in the bacterial cell wall, and therefore determines the phage specificity. Structural knowledge of baseplates will enable the rational engineering of phage host range. Before ejection, the phage genome is stored inside the capsid under high pressure. Although numerous studies of genome ejection have been performed, the understanding of this process is still incomplete because, until now, no suitable methods for studying in vivo ejection existed. The adsorption and genome ejection are closely related processes that can only be best understood together. In this project, hosted at Dr Plevka’s laboratory (CEITEC), I aim to determine the high-resolution structure of the phiKZ baseplate, one of the largest known bacteriophages, using cryogenic Transmission Electron Microscopy. The obtained structural information will be complemented by the characterisation of the genome ejection dynamics in vivo. For this purpose, I will use cryogenic Scanning Transmission Electron Microscopy to quantify the amount of DNA in phage heads at various stages of the infection. Furthermore, I will also use holotomography to visualise the ejection dynamics. There is still much to discover regarding bacterial adsorption and genome delivery. Thanks to my experience in phage and structural biology, I will integrate this project's results to shed light on the first steps of the phage life cycle, key to the infection of bacteria. My results will expand the understanding of phage infection and enable the retargeting of phages to specific bacterial strains, helping to develop phage therapy since antibiotic resistance is a rising health problem worldwide.

Mots clés : bacteriophage, genome ejection, myoviridae, cryogenic electron transmission microscopy, cryogenic scanning transmission electron microscopy

Participants :
- Université Masaryk (Rép. Tchèque) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 150438.72 €
Projet RENAISSANCE (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of nearly 25% i.e., affects one quarter of the adult population. Early phase NAFLD is reversible and can be treated, but it may progress towards life-threatening stages such as non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). The conventional diagnosis of NAFLD stages requires liver biopsy and is time-consuming and costly and there is an urgent need to identify biomarkers that can be applied in routine clinical settings, such as through blood-based testing. The identification of blood biomarkers would support earlier diagnosis and improved assessment of prognosis, ultimately supporting preventive/intervention measures to avoid progression to late stage liver disease and thus saving lives. In RENAISSANCE, a state-of-the-art liquid chromatography-high resolution mass spectrometry (LC-HRMS) metabolomics screening will be conducted upon the blood and blood-derived exosomes of a unique deeply phenotyped cohort of NAFLD patients for molecular biomarker discovery. Notably, exosome analysis shows promise for the identification of novel disease signatures but has yet to be applied to characterize NAFLD, providing high potential for the identification of new diagnostic/prognostic biomarkers for NAFLD. Furthermore, the LC-HRMS screen will be supported via targeted assays of redox metabolites and protein markers of acute inflammation. The integration of non-target and target data will provide insight into the underlying mechanisms of disease progression and further knowledge about potential causative factors of NAFLD.

Mots clés : nafld, metabolomics, biomarker discovery, liver diseases, nash

Participants :
- Université Masaryk (Rép. Tchèque) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 150438.72 €
Projet POL2PHASE (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

RNA Polymerase II (Pol II) plays a pivotal role in human cellular function, carrying out the complex transcription process. A unique domain sits at the end of Pol II, the C-Terminal Domain (CTD), the phosphorylation of which offers a mechanism of interaction for transcription factors (TFs) that regulate the transcription process. The spatial organization of TFs around Pol II is moderated by the intrinsically disordered regions (IDRs) of the TFs and CTD, and high specificity is required to avoid disease causing defects. However, the exact mechanisms that maintain this environment, and their importance are still unknown. Here we suggest a method for determining crucial Pol II – TF interactions by relating electromagnetic imaging to computer simulations. Results will be able to delineate individual amino acids responsible for maintaining the spatial organization of the proteins in vitro. The simulation-based study will be leveraged to explore the tolerance of maintaining these interactions when encountered with different phosphorylation states of CTD. A proof-of-concept study is then described which will demonstrate an ability to actively target IDRs to stabilize the protein interactions. While the results here will be comprehensive for four TFs of interest (RECQL5, SCAF4, SCAF8, and the SOSS1 complex), the methodology can then be expanded to characterize a library of over 400 TFs. Such a project has the potential to not only further our understanding of CTDs function, but also pave a way for designing synthetic treatments that can regulate the transcription process.

Mots clés : condensates, rna, polymerase, transcription, factors, nucleus, low complexity domain, intrinsically disordered region, intrinsically disordered protein

Participants :
- Université Masaryk (Rép. Tchèque) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 150438.72 €
Projet CD-ResOMics (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Crohn´s Disease (CD) is a chronic inflammatory disease that affects the gastrointestinal tract, affecting millions of people worldwide and presenting a considerable economic burden to health systems. CD has a serious impact in quality of life, not just physically, but also emotionally and socially. Pathogenesis results from a complex interaction between environmental factors, microbiome, genome, and inflammatory system, leading to disruption of the intestinal mucosa. The imbalance between inflammatory and regulatory cells in maintaining an active disease is well known, and most therapies aim to stop the cascade of inflammatory and pro-inflammatory cytokines (i.e. TNF-blockade). One of the major challenges for treatment is the fact that not all patients respond to therapy. Moreover, the mechanisms behind resistance are still not completely understood, making it hard to correctly stratify patients as responders and non-responders at time of diagnosis. We aim to elucidate changes in immune regulation that explain primary response failure to TNF-blockade in CD. We hypothesise that dysfunction of regulatory cells may prevent reinstatement of homeostasis following inflammation targeting. We will establish single-cell transcriptomics of immune cells from biopsies at the time of diagnosis, as well as in patients responding to treatment and non-responders. Then, we will use computational methods to investigate how immune cells change with time, acquiring a state supporting therapeutic resistance. Moreover, we will illuminate the relationship between immune dysregulation and anatomic niches using spatial transcriptomics. Finally, we will analyse paired peripheral blood samples, for the identification of putative biomarkers for stratification of patients according to TNF-blockade response. This proposal will provide unprecedented insights on the mechanisms involved in therapeutic resistance in CD, which could potentially lead to the development of new treatment approaches.

Mots clés : crohn s disease single cell transcriptomics spatial transcriptomics therapeutic resistance immune regulation

Participants :
- Gulbenkian Institute for Molecular Medicine (Portugal) — Coordinator, beneficiary, Recherche, subvention : 172618.56 €
Projet MicroDialogue (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The overuse of antibiotics has led to a disruption in gut microbiota, particularly in the Bacillota phylum, increasing susceptibility to pathogens, obesity, diabetes, and other metabolic disorders. MicroDialogue aims to evaluate the capacity of Quorum Sensing (QS) interspecies communication, a bacterial communication mechanism mediated by Autoinducer-2 (AI-2), to restore gut microbiota balance after antibiotic-induced perturbations and improve health outcomes. MicroDialogue will focus on the novel murine commensal non-pneumoniae Klebsiella sp. ARO112, which can provide colonization resistance against pathobionts, promote butyrate-producing bacteria, and produce AI-2, making it a promising candidate for promoting microbiota recovery. We hypothesize that manipulating AI-2 signaling with ARO112 can facilitate the recovery of the microbiota from antibiotic-induced dysbiosis. MicroDialuge’s main goal is to capitalize on the ability of ARO112, isolated by the host’s lab, to favor re-establishment of the Bacillota phylum while improving host immunity, via QS manipulation. To achieve this, we will manipulate the levels of AI-2 directly in the mouse gut using ARO112 WT and mutants already validated to assess the mechanistic effect of AI-2/ARO112 on axenic mice colonized with a defined microbiota. We will use metabolomics, and transcriptomics as part of a secondment at Jena University to reveal the molecular mechanisms involved in microbiota recovery. Additionally, we will test AI-2/ARO112-based therapies in mice colonized with a complex microbiota under antibiotic-induced dysbiosis. We will use CRISPR/Cas9 to modify ARO112 to track its colonization and flow cytometry to measure recovery of immune responses and inflammation. This research will expand our understanding of microbial QS and its potential to combat microbiota imbalances, with significant social and economic potential for human health by offering new strategies to mitigate the adverse effects of antibiotic use.

Mots clés : quorum sensing, gut microbiota, bacterial signaling, gnotobiotic mice, bacterial transcriptomics, host physiology, molecular microbial ecology, innate immunity and inflammation, dysbiosis

Participants :
- Université Friedrich-Schiller d'Iéna (Allemagne) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Gulbenkian Institute for Molecular Medicine (Portugal) — Coordinator, beneficiary, Recherche, subvention : 191343.12 €