Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet MOVES (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

The human voice is a powerful tool for social communication. In recent years, Artificial Intelligence (AI) fostered the development of advanced voice systems, able to infer considerable information from the speaker’s voice, such as emotional and mental states, mood information and personality traits. Individuals with schizophrenia (SZ) tend to present voice atypicalities, which are related to core clinical symptoms and social impairment. Recent advances in voice technology may lead the way to a revolution in the study of voice disorders. They may allow to disentangle the affective, cognitive and social mechanisms responsible for voice atypicalities, assist clinicians in diagnosis and monitoring of the disorders, and enhance their capability to capture the complex relationship between vocal behaviour, emotion regulation and clinical features. However, our present understanding of voice abnormalities in SZ is very poor, limited by the lack of comprehensive models and systematic approaches to study voice production. MOVES aims at providing a solid understanding of the implications of atypical voice patterns in SZ: through the application of machine learning and signal processing technologies (AI), I will provide a first comprehensive account of the mechanisms underlying voice atypicalities, assess their impact on clinical evaluations, and create the foundations for more reliable and evidence-based screening tools. The project aims to foster multi-centric and international collaborations to overcome important limits of this research field, such as the need for cross-linguistic studies, larger datasets, and open and collaborative research. MOVES pioneers a new area of research at the intersection between cognitive neuroscience, psychiatry, computational science and AI. An innovative aspect of the project is the intention to translate recent AI technological advances into clinical settings, to improve the way we conceptualise, assess and monitor voice disorders in SZ.


Participants :
- Aarhus University (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 207312.0 €
Projet xICE (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

The ice giant planets Uranus and Neptune are believed to play a crucial role in the formation process of our Solar System and are prototypical for hundreds of exoplanets, so-called mini-Neptunes, which are discovered at ever increasing speed thanks to planet-hunting missions like Kepler, TESS, and PLATO. Modeling the interior structure, magnetic dynamo, and thermal evolution of Uranus and Neptune has proven very challenging relying only on the Voyager 2 flyby data from the 1980s and ground-based observations. The key to improve these models is to investigate interfaces and thermal boundaries resulting from the properties of the material in their deep interiors. Hence, we perform molecular dynamics simulations on multiple scales to derive additional modeling constraints, which are experimentally challenging to obtain or even inaccessible. We use accurate ab initio simulations to calculate a new equation of state to constrain the rock/ice ratio in planetary interior models. Subsequently, we fit potentials to the ab initio data to investigate up to 1 million atoms using classical molecular dynamics. For the first time, we are able to explore interfaces between the inner mantle and the core of an ice giant planet on a atomic level. The resulting thermal and transport properties will be used as essential inputs for novel interior structure and magnetic dynamo models for ice giant planets; particularly those in our Solar System. The project results will enhance the fellow's career prospects, make a significant contribution to the science excellence in Europe, and especially strengthen the science case for future Uranus and Neptune missions by ESA and NASA.

Mots clés : warm dense matter, ab initio simulations, first principles, density functional theory, molecular dynamics, high temperature, equation of state, transport properties, phase diagram, superionic phase

Participants :
- École normale supérieure de Lyon (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 184707.84 €
Projet STARPAC (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The immune response to cytosolic DNA is crucial for preventing tumour formation and virus infection. This response critically depends on the cGAS-STING pathway, which detects cytosolic self-DNA present in tumour cells and viral DNA. STING can also detect cytosolic self-DNA induced by upon RNA virus infections, and numerous RNA viruses have evolved strategies to disable STING. STING activation is a complex process that requires various post-translational modifications, leading to STING trafficking and activation at the Golgi apparatus. STING activation induces the transcription of genes that promote immune cell recruitment. Aberrant STING regulation may lead to virus infections, inflammatory disorders, and tumour formation. Many of the regulators involved in STING activation are unknown. To identify host factors regulating STING activity, I recently performed a genome-wide CRISPRi screen (Luteijn et al, 2019, Nature). I found many novel genes involved in STING activation, including the Golgi protein ACBD3. This protein localizes the phospholipid phosphatidylinositol 4-phosohate (PI4P) to the Golgi membrane by recruiting the PI4P kinase PI4KB. My preliminary work revealed that STING activation in the Golgi critically depends on ACBD3 and PI4P. Remarkably, ACBD3 and other PI4P-associated factors are also targeted during infection by certain RNA viruses. It is completely unknown how ACBD3 and PI4P distribution affect STING activity, and if PI4P hijacking by RNA viruses modifies the STING-induced immune response. This project has 3 main objectives: 1. Define the role of ACBD3 and PI4KB expression and function on STING activation 2. Identify and target regulators of PI4P biology to increase STING activity 3. Define the role of PI4P hijacking by RNA viruses on STING immune evasion Understanding how ACBD3 and other PI4P-associated factors regulate STING will lead to the identification of novel therapeutic targets to combat tumours, virus infections, and inflammation.

Mots clés : sting, phosphatidylinositol 4 phosohate, membrane trafficking

Participants :
- Utrecht University (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187572.48 €
Projet ZF-ILC (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The immune system can be subdivided into two main arms: the innate and the adaptive. Recently, it was identified a new family of cells belonging to the innate system but that phenotypically and functionally resemble the specific subtypes of adaptive T lymphocytes. In mice and in humans, these innate lymphoid cells (ILCs) play critical roles in host defense, in shaping the microbiota and in tissue repair at mucosal tissues via secreting cytokines such as IL-22. The innate system is more ancient than the adaptive, however, the existence and diversity of ILCs in organisms other than mammals remains unknown. Also unknown is how ILCs interact with other cells within tissues. This project will address the existence and role of the different subsets of ILCs and the conservation of IL-22 function in a distant relative, the zebrafish, a genetically tractable vertebrate with remarkable optical accessibility. To identify ILCs, cell populations likely enriched in these cells will be purified from mucosal sites such as the intestine and the gills by flow cytometry, guided by morphology and expression of reporter transgenes for immune cell types. Their transcriptome profile will be assessed in bulk and at the single-cell level adapting the microfluidic-based Biomark system to the zebrafish. Also, to know if cytokines produced by T cells can also be produced by non-adaptive lymphocytes – i.e., ILCs, as described in mouse, immune responses of zebrafish mutants lacking adaptive lymphocytes or all types of lymphocytes will be compared to that of wild-type fish. To study IL-22 function, mutants for this cytokine and its receptor will be generated. Together with a transgenic il22 reporter line allowing the identification of IL-22-producing cells, they will be challenged with pathogens or inflammatory stimuli, and studied by various approaches including in vivo imaging. This work will allow a detailed in vivo study of the ontogeny, role and behavior of ILCs and IL-22- producing cells.

Mots clés : innate lymphoid cells, il 22, zebrafish, mucosal immunology, immune system development, comparative immunology

Participants :
- Institut Pasteur (France) — Coordinator, beneficiary, Recherche, subvention : 173076.0 €
Projet RhomBioID (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The immune system coordinates vital responses against a plethora of threats. It relies on well-described signalling networks via soluble proteins and cell-to-cell contacts. The secretory pathway traffics all secreted and surface proteins, but the mechanism of how immune cells control this process is unclear. Rhomboid-like proteins are a family of polytopic intramembrane proteins serine proteases and pseudoenzymes found in all organisms. Most eukaryotic rhomboid-like proteins regulate the fate of proteins in the secretory pathway. The rhomboid protease RHBDL4 is reported to regulate ER associated degradation (ERAD). The rhomboid pseudoenzyme, iRhom2, is essential for the trafficking and maturation of TACE, and subsequent TNF release in response to inflammatory stimuli in myeloid cells. Little is understood about the mechanism of how these rhomboid-like proteins regulate trafficking. I hypothesise that RHBDL4 regulates signalling networks in myeloid cells, similarly to iRhom2. Indeed, according to my preliminary data, RHBDL4 and iRhom2 are both expressed in human myeloid cells, and are induced by interferon gamma, a modulator of signalling networks in immunity. In this project, I aim to provide cell biological and mechanistic insight into RHBDL4 and iRhom2 regulation of signalling networks in human immunity. I will identify new interactors of RHBDL4 and iRhom2 via a novel biochemical screen called BioID. Candidates will be validated using conventional cell biological methodologies and a new interaction assay called M-Track. I will confirm these interactions in a quasi-physiological context, using a human ex vivo macrophage system. The biological significance of the interactions will be studied using detergent-permeabilised cellular systems of human macrophages. My focus on human rhomboids and immunity integrates a very timely area of fundamental cell biology with a topic of direct relevance to human health.

Mots clés : rhomboid like proteins, proteases, rhbdl4, irhom2, traffic in immune cells, macrophage activation, bioid, biochemical screen, human immunity

Participants :
- University of Oxford (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet SONAR-CO2 (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

The impact of anthropogenic ocean acidification on calcifying organisms is expected to be imminent, particularly in high latitude ecosystems. Coccolithophores are the most abundant calcareous phytoplankton in the ocean and play a key role in the global climate by contributing to the oceanic pumps of organic matter and carbonate. Many laboratory experiments suggest that the increasing CO2 levels in the ocean will produce a transition in dominance from more to less heavily calcified coccolithophores. However, this point remains controversial. The Southern Ocean, contains about 40% of the global inventory of anthropogenic atmospheric CO2 with much of the drawdown occurring in the Sub-Antarctic Zone or SAZ. This large inventory of anthropogenic CO2 together with the relatively small changes in other chemical and physical variables in the surface layer of the SAZ makes this region an ideal setting to examine the response of marine calcifying plankton to increasing anthropogenic CO2 levels in their natural habitat. Indeed, there is evidence that the ongoing ocean acidification in the SAZ is already affecting the calcification of key calcifying plankton such as planktonic foraminifera. Coccolithophores are thought to be the main contributors of the elevated Particulate Inorganic Carbon (PIC) concentrations in the waters of the Subtropical, Subantarctic and Polar Fronts. However, despite the importance of coccolithophores in the subantarctic ecosystems, their composition, abundance, seasonality and calcification response to increasing CO2 levels are poorly characterized. In the proposed Marie Curie project, we will combine the analysis of the coccolithophore assemblages collected by an automatic surface layer sampler, sediment traps and sediment samples from two sectors of the Subantarctic Zone. The water and sediment trap samples represent the late industrial era, while surface sediment and sediment core samples are used as a pre-industrial baseline.

Mots clés : ocean acidification, coccolithophores, southern ocean, subantarctic zone, biomarkers

Participants :
- Universidad de Salamanca (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 158121.6 €
Projet AMORPHORM (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : TERMINATED

The importance of amorphous water-soluble substances has been increasingly recognized over last two decades in the pharmaceutical and food industries. Amorphous solids of small molecules offer a solubility advantage over their crystalline counterparts. Parallel to that, large molecular systems, such as proteins and enzymes, are difficult to crystallize but are often stabilized in amorphous formulations. Amorphous systems are inherently unstable and hence more prone to physico-chemical changes. In order to increase the safety and reduce the risk of their usage for both human patients/customers and industry it is necessary to determine their long-term physico-chemical stability. There is currently no existing reliable and widely applicable method for stability testing of amorphous formulations. During my research I have demonstrated such a method can be based on a terahertz spectroscopy, which probes the mobility of molecules when they are solids. I found that this approach is universal and should be able to be applied for all hydrogen bonding solids, which spans almost all organic compounds. The objectives of the proposal can be split into 3 blocks. The technology block will focus on developing terahertz spectroscopy into a reliable stability testing method to industrial standards and to explore whether more affordable instrumentation can be deployed alternatively to reduce the capital cost of the method. In the pharmaceutical block we will aim to determine how pharmaceutical formulation and processing steps can be optimised for amorphous stability. We will examine also critical storage conditions for the amorphous products and how to prevent any recrystallization during their dissolution. In the food and biotechnology block we will aim to transfer the methods developed for small drug molecules to protein and enzyme preservation in glassy matrices.

Mots clés : amorphous, glass, supercooled, stability, crystallisation, molecular mobility, solubility, formulation, pharmaceutical, spectroscopy, thermal analysis

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212194.8 €
Projet ProMeta (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The importance of an insight into how cell fate is established and maintained, extends far beyond the interests of developmental biology. It is pivotal to our understanding of how these processes can be hijacked and deranged in diseases such as cancer, or of the factors involved in reprogramming cell identity and function. Acute Myeloid Leukaemia (AML) has a dismal prognosis with less than 30% 5-year survival. Mainstay therapy has remained essentially unchanged for the past three decades, with all small advances in disease-free survival attributable to transplantation and improved supportive care. Only recently PKC412 has received Food and Drug Administration (FDA)’s break through therapy designation for the FLT3-ITD+ AML. This paves the way for investigation considering that FLT3-ITD as a driving oncogenic mutation has been found in ~30% of the AML patients. The pathogenesis of AML is heterogeneous, but there are common themes of epigenetic, transcriptional and signalling dysregulation that contribute to the resulting clonal expansion of blasts at different stages of maturation, and accompanying bone marrow failure. A significant number of the most commonly mutated targets in AML are histone modifiers, i.e. proteins or complexes that catalyse post-translational modifications in specific residues of the histone side chains. A less studied acetyltransferase, but crucially implicated in AML is KAT2A, the first histone acetyl-transferase (HAT) identified in yeast.GCN5 also acetylates the AML1/MDS1/EVI1 fusion protein in rare cases of AML.KAT2A regulates the activity of Peroxisome Proliferator- Activated Receptor Gamma-Coactivator-1α and B through protein acetylation. The goal of this proposal is to explore the role of KAT2A in Acute Myeloid Leukaemia (AML) through investigation of its non-histone protein acetylation activity.

Mots clés : cancer, kat2a, metabolomics, mass spectrometry, non histone proteins, nuclear magnetic resonance

Participants :
- University of Cambridge (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet AsymFeCH (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

The importance of chirality in bioactive molecules is well established with only one enantiomer exhibiting the desired biological activity. To date, more than 90% of chiral drugs on the market are supplied as racemates potentially causing side-effects or of uncertain bioactivity. The enantioselective synthesis of chemicals has risen to address such issues with enantioselective catalytic C–H activation standing out due to its atom economy, step efficiency, and avoidance of substrate pre-functionalization. So far, metal-catalysed enantioselective inner sphere C–H activation relies mainly on precious and/or toxic metals, such as Pd and Ru, limiting the reaction’s applicability. Therefore, efforts are currently being made to replace such metals with more benign 3rd row transition metals. Nevertheless, only one report of such transformation has been reported with Fe despite Fe being extremely desirable due to its low cost, toxicity and high natural abundance. The AsymFeCH project will address this issue through the development of non-toxic, sustainable and inexpensive Fe-catalysed enantioselective C–H activation reactions. For this purpose, low valent Fe complexes with chiral phosphines will be used as precatalysts in the catalytic hydroarylation of allenes or alkenes with aromatic ketones. The mechanism and origin of enantioselectivity of the developed reactions will then be delineated through a unique combination of spectroscopies and kinetic studies. Subsequently, the acquired mechanistic understanding will be used for further reaction development with more challenging substrates (imines and 1,1-diphenylketone derivatives) setting the foundations for the scientific and industrial communities to advance the field of asymmetric Fe-catalysed C-H activation. This will not only lead to the sustainable and greener synthesis of pure chiral products affecting the pharmaceutical and materials sectors but will also make Europe less dependent on Pd, an imported precious metal.

Mots clés : catalysis, iron, c h activation, asymmetric, mechanism

Participants :
- University of Göttingen (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 162806.4 €
Projet SYNOX (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

The importance of natural products and derivatives as sources of new drugs is undeniable. Newman has stated: "It is probably true that if one had to name the natural product that has saved the most lives.....penicillin G would be the molecule of choice" (D. J. Newman, G. M. Cragg, in Natural Product Chemistry for Drug Discovery, Chapter 1, RSC Biolmolecular Sciences No. 18, 2009). In this proposal we will develop methodology for the synthesis of two types of closely related natural products which have wide-ranging biological activities including: anti-bacterial, anti-viral, anti-tumour and herbicidal activity; but whose biological activities have not been fully evaluated. We will use our recently developed oxidative radical cyclisation methodology to synthesise the cores of these biologically relevant natural products and develop new methodology for the direct functionalisation of certain aromatic heterocycles as part of the synthesis of the unsaturated portions of the natural products. The biological activities, particularly with respect to anti-bacterial and anti-tumour properties of all of the key synthetic intermediates (simplified analogues) and synthetic natural products themselves will be assessed. The project is divided into four work packages involving: i) development of direct functionalisation certain aromatic heterocycles; ii) synthesis of the the one type of natural product; iii) oxidative radical synthesis of natural product cores; iv) total synthesis of the second type of natural product.


Participants :
- University of Oxford (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €