Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet 4D Development (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

How the genome regulates the differentiation trajectories that instruct a single fertilised egg to develop into an adult organism is a longstanding question in biology. Here, high-throughput spatial transcriptomics will be leveraged to virtually measure all cellular states of the Drosophila melanogaster. The entire ten-day development of the fruit fly will be sampled with a four-hour interval, where the spatial gene expression of 1,600 genes will be measured in a serially sectioned fly at single cell resolution. The sections will subsequently be reconstructed into 3D models. This approach enables whole-body-biology where a complex measurement is taken of all cells of an entire individual and is here used to densely sample development.  In order to reconstruct differentiation trajectories, the 3D fly models will be anatomically aligned between timepoints so that cellular states can be linked and transitions in transcriptional profiles can be studied. The spatial information will substantially simplify this challenge because progenitors and putative progeny will be in the same anatomical compartment. This will generate a 4D developmental model of the fruit fly that links cells, cell types, anatomy and differentiation in space and time.  The 4D developmental fly and the cell type trajectories will serve as the manifold onto which single cell transcriptomics (RNA-seq) and chromatin accessibility (ATAC-seq) data will be integrated. Then, Gene Regulatory Network inference tools can be used to identify transcription factors and enhancer sequences that drive lineage decisions. Investigating the enhancer sequences will reveal how cell type specificity is encoded and how the arising complexity is regulated during development. This project will give a unique insight into development, patterning and the emergence of cellular diversity from the genome, and will form an important proof of concept to approach development in other larger organisms such as mice and humans.

Mots clés : spatial transcriptomics, gene regulatory networks, drosophila melanogaster, smfish, merfish

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 191760.0 €
Projet HeartRepairKIT (Horizon Europe, appel à projets 2023)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

KIT, a receptor tyrosine kinase, is dimerized at the cell surface by the cytokine stem cell factor (SCF) to initiate signalling pathways securing fundamental cellular processes, including hematopoiesis, gametogenesis, and melanogenesis. Impaired signalling due to KIT mutations or deficiency leads to various malignancies such as leukemia and melanoma. However, recent data have shown that KIT can also initiate signalling by binding meteorin-like protein (METRNL), triggering unrelated stimulation of heart tissue regeneration. Ischemic heart diseases are the leading cause of mortality and morbidity worldwide, with approximately 9 million annual deaths and over 180 million disability-adjusted life years lost. Therefore, revealing the molecular principles and mechanism of this completely new function of KIT gives hope for new opportunities towards novel therapies that might maximize the efficiency of heart recovery after heart disease incidence. However, the field is currently plagued by a paucity of mechanistic details and the structure-function relationship of the KIT.METRNL complex assembly. The goal of this project is to derive the structure-function landscape of the novel interaction between KIT and METRNL and to provide a blueprint for how KIT can be activated by two structurally distinct protein ligands. The gained knowledge will govern the rational engineering of METRNL towards improving its interaction with KIT to elicit intensified signalling that can lead to amplified heart tissue regeneration. This aim will be achieved by synergistically combining methods of molecular and structural biology (supervisor’s expertise), biomolecular kinetics and rational protein engineering (researcher’s experience), and single molecule biophysics (secondment). Collectively, this research endeavour will impact basic and applied cardiovascular disease research and promises to provide new possibilities for alleviating the enormous socioeconomic burden associated with these diseases.

Mots clés : kit, receptor tyrosine kinase, meteorin like, stem cell factor, myocardial infarction, biomolecular kinetics, single molecule biophysics, protein engineering, drug design, protein protein interactions

Participants :
- Université d'Osnabrück (Allemagne) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 191760.0 €
Projet EnviBrain (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : TERMINATED

Although chemicals enable a constant improvement of health, life quality and facilitate food production, industrial applications and advanced agricultural practices, their release into the environment may be followed by increased risks for human health. Humans (directly or indirectly) are exposed to a diverse mixture of chemicals through multiple pathways, which has been acknowledged to play an important role in common chronic diseases, including multiple types of cancer, but the specific exposure-disease associations have not been explored sufficiently in many cases. This is particularly relevant for brain tumors, whose causes are still unknown, and it is suspected that the environmental components may play an important role since less than 5% of patients have a family history. Diffuse gliomas are the most common primary malignant brain tumors in adults with poor prognosis and survival, therefore, identifying environmental contributions to diffuse gliomas development and investigating links with chemical exposures is crucial for improving prognosis and treatment options. The objectives of this fellowship are (i) to explore the chemical exposome (exogenous chemicals and associated metabolites) of brain tumor tissues by making use of a unique historical cohort of diffuse gliomas patients (Bellvitge Glioma Cohort; Hospital de Bellvitge; 2005-present) and (ii) assess the exposure of Barcelona citizens to a mixture of contaminants through the analysis of air particulate matter, wastewater and sewage sludge. State-of-the-art analytical chemistry techniques and data science methods will be integrated to identify potential toxic organic chemicals and their metabolites/transformation products in the environment, that may influence the development of diffuse glioma in Barcelona. The generated results can be used by competent authorities to establish more surgical measures to reduce the emission of very hazardous chemicals and improve both air quality and population health.

Mots clés : high resolution mass spectrometry non target screening emerging contaminants wastewater based epidemiology human health brain cancer

Participants :
- Conseil supérieur de la recherche scientifique (Espagne) — Coordinator, beneficiary, Recherche, subvention : 181152.96 €
Projet RedoxBoost (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Various environmental stress conditions in plants lead to oxidative stress and trigger damage to macromolecules causing losses in the crop yield. To better cope with oxidative stress via boosting the redox potential, and antioxidant activity, the RedoxBoost project aims to ectopically express the selenoprotein glutathione peroxidase from Chlamydomonas reinhardtii (Sec-CrGPX) in Arabidopsis thaliana. Selenoproteins entail a selenocysteine (Sec) amino acid, encoded by the UGA, which encodes stop codon in higher plants. Thereby, selenoproteins are not present in higher plants but present in eubacteria, archaea, and eukaryotes including green algae. Most of the known selenoproteins were involved in antioxidant activity, redox regulation and are more resistant to irreversible oxidation under severe oxidative stress than their cysteine homologs. I hypothesize that heterologous expression of selenoproteins in higher plants might offer an excellent opportunity for harnessing plants against oxidative stress and hence develop more stress resilient plants. Glutathione peroxidase is one of the most abundant selenoproteins and known to protect cells from oxidative damage. To achieve heterologous expression of Sec-CrGPX in Arabidopsis, initially a DNA assembly of whole Sec biosynthetic pathway and Sec-CrGPX will be transiently expressed in Nicotiana benthamiana to get a swift assessment on the feasibility of ectopic Sec-CrGPX expression in land plants. Then, these Sec-CrGPX DNA assemblies will be stably transformed in Arabidopsis. RedoxBoost for the first-time will integrate the coding mechanism for Sec in higher plants. Biochemical and physiological studies will be performed in transgenic Arabidopsis plants under different stress conditions to determine altered stress resilience. In a changing environment where flooding, waterlogging conditions, and saline soils are becoming more frequent RedoxBoost presents a novel approach for development of stress resilient plants.

Mots clés : selenoprotein, selenocysteine, antioxidant, redox regulation, arabidopsis, 

Participants :
- Université de Technologie de Kaiserslautern (Allemagne) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 191760.0 €
Projet NeuroTalk2Mi (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Microglia are the resident immune cells of the brain, display extensive heterogeneity, and contribute to a wide range of cellular processes in both homeostasis and disease. They play a major role in the pathogenesis of Alzheimer’s disease (AD), the leading cause of dementia and a major cause of mortality worldwide. Microglia closely interact with neurons and modulate their function with high regional specificity, making them potential culprits behind the neuronal damage in AD. However, exactly how microglia and neurons interact and communicate, and how these interactions change in disease is not known. I hypothesize that an early hallmark of AD is the changing interactions between microglia and neighboring cells such as neurons, which contributes to progress of the disease and ultimately results in synaptic and neuronal loss. I will test this in human microglia by using a unique human xenotransplantation model, whereby I transplant human pluripotent stem cell-derived microglial progenitors into the cortex of healthy and AD mice. Using RABID-seq combined with 10X Genomics to barcode microglia and subsequently trace their interactions with single-cell resolution, I will precisely map the interactions of distinct subsets of microglia and neurons, to determine homeostatic molecular networks and how cell-to-cell communication is altered in the early stages of AD. Ultimately, this will allow me to identify specific molecules and molecular pathways which can be manipulated to support a beneficial function in microglia, while blocking detrimental effects, to protect neurons and prevent, slow, or ameliorate the disease. Given that microglia are involved in normal brain development and multiple neurodegenerative diseases, finally dissecting how they interact with other cells of the CNS will be a valuable resource to the greater neuroscience community with implications for development, ageing, and disease.

Mots clés : microglia, neurons, communication, single cell interaction tracing, rabid seq, neurodegeneration, alzheimer s

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 191760.0 €
Projet DIASPOREP-EU (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : SIGNED

In a time of democracies’ crisis of legitimacy, new faces of political representation are renewing our understanding of democratic representation. Among them, Diaspora organisations (DOs) have emerged as key transnational actors engaging with public and private institutions, governments, and civil societies at all levels. This research examines the contemporary building of diaspora claims for representation at the European level. It aims at shedding light on the framing process of the demand for non-elective political representation expressed by umbrella organisations, networks and platforms of European citizens and residents with migrant ancestries and diasporic ties, within the EU institutional bodies and multi-level and multi-actors arenas led by the EU. To address it, my research explores three closely connected research objectives: (1) The diverse faces of diaspora civil society representative organisations in Europe today (2) The framing process of the diaspora organisations representative claims (3) The legitimizing of non-elective representation of diasporas in Europe. Anchored in political sociology, my research framework is cross-disciplinary and brings together diaspora studies and democratic representation studies. It builds on a mixed-methods design with a strong qualitative leaning, and is partly co-designed and disseminated in collaboration with the European instrument EUDiF. My research addresses a topical issue and aims at offering both empirical and theoretical contributions to academia (7 communications, 3 articles, 1 special issue), and to practitioners, activists and policy-makers (Web publications, conference, non-academic communications, fact sheet, policy brief, outreach meeting). This 2 year project will be supervised by Pr Jean-Michel Lafleur, hosted at the CEDEM research unit, ULiège, and builds on two strong research collaborations with the IMISCOE research network and the EU Diaspora Facility (EUDiF).

Mots clés : diaspora organizations, non elective political representation

Participants :
- Université de Liège (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 216240.0 €
Projet Photo2Olef (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Light olefins have been considered fundamental feedstocks in the chemical industry for decades. Current industrial processes for the synthesis of light olefins include naphtha cracking and light alkane dehydrogenation in thermochemical processes are under harsh conditions, and therefore energy-intensive. In the last decade, the solar-to-chemicals conversion process has attracted great attention, as it is deemed that the utilization of solar energy for the replacement of traditional fossil fuels is an ideal solution to the energy crisis and global warming. However, even though several reaction processes have been extensively studied and progress has been achieved, such as photocatalytic water splitting and photothermal/photocatalytic CO2 reduction, light-assisted alkane dehydrogenation reactions for the sustainable production of alkenes has not been explored yet. The objective of this research proposal is twofold: 1) developing new catalyst based on trimetallic clusters confined in Zr-based MOFs (TMC-MOF) for the photo-assisted light alkane dehydrogenation under mild conditions (<150oC), and 2) understanding the mechanism of the photo-assisted process, providing principles for design more efficient catalysts. The present project represents a significant step forward by showing the applicability of the solar-assisted alkane dehydrogenation process, presenting a significant advantage in terms of CO2-footprint.

Mots clés : photo assisted catalysis, alkane, dehydrogenation, olefine, trimetallic cluster, mof, mild temperature

Participants :
- Leibniz-Gemeinschaft (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 189687.36 €
Projet 4GETasthma (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Asthma is the most common chronic lung disease. In most asthmatics, allergen-specific type-2 CD4 T cells orchestrate allergic airway inflammation by producing type-2 cytokines that ultimately drive asthma pathology. Studies suggest that a subset of long-lived memory Th2 cells that reside in the lung, known as tissue-resident memory Th2 cells (T2RM), play a significant role in driving asthma chronicity and persistence. Therapies aimed at depleting T2RM from the lung represent a novel approach to treating asthma, however factors that regulate the generation and persistence of lung-T2RMs remain poorly understood. I hypothesize that distinct and druggable molecular pathways control lung-T2RM survival and re-activation. This work aims to decipher molecular and cellular mechanisms that regulate the maintenance and re-activation of T2RM within the asthmatic lung niche. The host lab has recently developed a novel TCR transgenic (Tg) mouse line (1DER-CD5), containing a monoclonal population of house dust mite (HDM) specific CD4 T cells with high T2RM differentiation potential, which has been confirmed in preliminary experiments performed since joining the host lab. In WP1, I will perform single cell transcriptomic and proteomic analysis on 1DER-CD5 T cells in the lungs of mice in the memory phases of HDM-induced asthma to predict molecular and cellular networks that regulate lung-T2RM. In WP2, I will utilize targeted spatial transcriptomics, paired with confocal microscopy, to define the lung-T2RM niche and validate molecular and cellular interactions predicted in WP1. In WP3, I will use an in vivo CRISPR-screening approach with Cas9+ 1DER-CD5 T cells to pinpoint key druggable pathways that regulate lung-T2RM survival and re-activation. This work is expected to identify molecular pathways critical in regulating the persistence and re-activation of lung-T2RM, potentially leading to the development of novel therapies to deplete pathogenic T2RM from the airways of asthmatics.

Mots clés : tissue resident memory t cells, asthma, allergy, immunological niches

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 200400.0 €
Projet MAVS in plants (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Rhizomania is one of the most economically devastating disease of sugar beet and is caused by Beet necrotic yellow vein virus (BNYVV). Emerging evidence indicates that mitochondria plays essential role in plant immunity and thus represents a promising target for the development of sustainable broad-spectrum disease resistance in crops. This project builds on the previous findings that BNYVV localize to mitochondria, and this occurrence is related to the assembly of the virus. Moreover, several nuclear genes encoding mitochondrial proteins appear to be repressed by a nuclear-localized BNYVV P25 virulence factor (Savenkov, unpublished). In animals, mitochondrial signaling in response to virus infection has been well studied, but it has been overlooked in plants and still is an open field to find the potential targets for improved plant fitness against plant viruses. Mitochondria activate antiviral signaling in response to virus infection in animals, but so far no such mechanism is known in plants. The mitochondria exert its response via nucleus by a process called mitochondrial retrograde regulation (MRR). Mitochondrial homeostasis translates pathogen infection into molecular mechanisms associated with chromatin remodeling thereby conferring resistance to pathogens. Mitochondria remodel chromatin structure via MRR and activate defense related genes to fight off the pathogen. The rationale behind this proposal is discoveries from the host’s group showing that promoter elements of mitochondrial genes (Tim13, Cyt c) are the targets of p25 protein of BNYVV (as was identified by ChIP-seq; unpublished data). This project has the overarching aim to deepen our understanding of the mitochondrial events underlying antiviral response, with the long-term goal to provide knowledge-based tools for improved plant performance under pathogen attack.

Mots clés : mitochondrial, virus, mitochondrial retrograde regulation, p25

Participants :
- Université suédoise des sciences agricoles (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 206887.68 €
Projet PREENER (Horizon Europe, appel à projets 2021)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Plant-parasitic nematodes are microscopic organisms with exceptionally broad host range that pose major challenge to global agriculture, generate a predicted loss of 12.3 percent, equivalent to $157 billion each year. The losses caused by nematodes are further enhanced when they form disease-complexes with other microbes. Endoparasitic cyst nematodes are one of two most devastating groups, infecting the roots of economically important plants. The nematodes are a persistent problem because they have evolved an ability to secrete specific proteins to exploit the host plant’s development and suppress defense responses triggered by the plant. They begin feeding only after developing a specialized feeding structure (syncytium) inside the host root, by selecting a single cell near the innermost nutrient-rich vascular tissues, causing cellular injury by passing through multiple layers of different cell files. The majority of previous research has been on syncytium formation as infection proceeds. However, it is unknown how plants respond at the cellular level to the mechanical damage caused by nematodes, which prevents the creation of resistant plants to minimize crop losses. In the proposed study, cells from two internal consecutive cell layers surrounding the vascular tissues will be studied for their molecular responses to mechanical injury. The control of lignin and suberin production, which function as physical barriers against invading pathogens, will be studied in particular. Advanced microscopic technology will be utilized to accurately produce mechanical damage in selected internal root cells using a cutting-edge method called laser ablation. It will offer a strong platform for the creation of resistance agricultural plants against plant parasitic nematodes in the long run. The project will use a variety of high-tech multidisciplinary approaches to provide a framework for researching plant physical barrier measures against invasive plant diseases.

Mots clés : plant nematode interaction, mechanical injury, lignin, suberin, cellular responses, laser ablation

Participants :
- Université rhénane Frédéric-Guillaume de Bonn (Allemagne) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Université suédoise des sciences agricoles (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 222727.68 €