Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet DSMT16 (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

An association between inflammation and carcinogenesis is well established, however, how they are related mechanistically in subtypes of sporadic intestinal tumours remains unclear. This study aims to decipher how oncogenes determine the inflammatory microenvironment (stroma) and how this affects tumour development and survival. Notably, intestinal epithelium-specific expression of oncogenic Kras(G12D), Braf(V637E) and Pik3ca(H1047R) in mice mimics serrated intestinal cancers in humans faithfully. Preliminary data suggest that the mutational make-up of the tumour may dictate the pro- and anti-tumourigenic immune response, which in turn determines tumour development and survival. This study therefore aims to characterise the tumour-infiltrating immune cells by systematic immunophenotyping and to decipher the involved inflammatory signalling mechanisms in a cell-type and mutation-specific manner. Moreover, we aim to reconstruct the formation of the oncogene-specific inflammatory microenvironment, which we will determine via endoscopic transplantation of intestinal organoids derived from Kras(G12D), Braf(V637E) and Pik3ca(H1047R) mice into the large intestine of wild-type mice. Importantly, detection of involved inflammatory mediators and immune cell-subtypes will allow us to genetically target them in vivo using novel in-house generated dual-recombinase systems (DRS). In order to investigate the consequences of inflammation on sporadic intestinal tumourigenesis, models with genetically or experimentally induced chronic inflammation will be applied. Conversely, immunodeficient Rag2;Il2rg–/– mice will be used to elucidate if sporadic intestinal carcinogenesis in Kras(G12D), Braf(V637E) and Pik3ca(H1047R) mice is dependent on inflammation and can be abrogated. This study will generate new mechanistic insights into the microenvironment of cancer subtypes, which could provide a basis for the development of new personalised immune therapies.

Mots clés : signal transduction, oncogene induced inflammation, tumour microenvironment  stroma, transgenic mouse models, cancer disease models

Participants :
- Technical University of Munich (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 159460.8 €
Projet DiseaseRecognition (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

An astounding example of human social complexity is the global healthcare industry, in which we perform lifesaving surgeries, eradicate childhood diseases, provide global vaccinations, and track the evolution and outbreak of novel zoonotic diseases. Surprisingly, all of this hinges on a cognitive ability whose evolutionary origins are largely unknown: the ability to recognize disease in others. Under the mentorship of Dr Joanna Setchell (Durham University), a world-leading expert in primate disease signalling, Dr Sharon Kessler (fellow) will test her novel hypothesis that disease recognition evolved in associate with social cognition the primate order before the divergence of the human lineage. This multidisciplinary project integrates anthropology, psychology, and parasitology to test 1) whether a nonhuman primate signals infection status using visual, acoustic, and olfactory cues, 2) whether primates use these cues to recognize disease in others, and 3) whether disease recognition correlates with accepted measures of primate social cognition. The objectives will be achieved by taking photos, recording vocalisations, and collecting odour samples from semi-free ranging mandrills, Mandrillus sphinx, at the Centre International de Recherches Médicales mandrill colony in Gabon before and after treatment with anti-parasite medications. The photos, vocalisations, and odour samples will be presented to captive mandrills at the Colchester Zoo in the UK to test whether they spend different amounts of time investigating stimuli from parasitised and nonparasitised individuals. Performances on these disease recognition tests will be compared with performances in social cognition on the state-of-the-art Primate Cognition Test Battery. This innovative, multidisciplinary study increases the international networks of the participants, provides Kessler with cutting edge training, and breaks new ground on the role of disease in the evolution of primate, including human, cognition.

Mots clés : primatology, social cognition, disease transmission

Participants :
- Durham University (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet GRITAP (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

An attractive approach to preparing molecules with common repeat units is iterative synthesis, an approach that is extensively used by Nature in the synthesis of large biomolecules. Nature also uses this tactic for small-molecule synthesis even though common repeat units are not always immediately apparent, the archetypical example being polyketide synthesis. In contrast, iterative strategies in chemical synthesis are often much less efficient requiring several functional-group interconversions and purifications between chain-extension steps. We recently reported an “Assembly Line Synthesis” method for the iterative, reagent-controlled homologation (chain extension) of a boronic ester. This process enabled the conversion of a simple boronic ester into a molecule bearing 10 contiguous methyl substituents in an effectively “one-pot” process. Whilst these methyl-rich carbon chains are rare in natural products, hydroxyl-rich carbon chains (1,3-polyols) are ubiquitous and often show pronounced and useful biological activity. It would therefore be very useful if this or a related strategy could be applied to the fully stereocontrolled synthesis of 1,3-polyols. Herein, we outline a general strategy for the synthesis of 1,3-polyols that hinges on the merging of two well-established methodologies: lithiation–borylation and catalytic diboration. We expect to achieve complete control over both relative and absolute stereochemistry in the iterative synthesis of 1,3-polyboronic esters, enabling stereochemistry to be essentially dialled-in. Subsequent oxidation of the boron esters reveals the desired 1,3-related polyol. The strategy will be applied to the total synthesis of one of the most complex polyols known, bahamaolide A, a macrocyclic polyol–polyene natural product with potent antifungal properties. This strategy promises to be the most efficient synthetic route to these highly biologically active and hugely important class of compounds.

Mots clés : boron, stereoselective, polyol, total synthesis, polyketide

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

An epoch of “big data” mining just started for high redshift astronomy. State-of-the-art photometric surveys observed millions of objects on sky, and next-generation telescopes will provide statistically significant samples even for the rarest galaxy types. However, standard techniques (e.g., methods to fit galaxies' spectral energy distribution) are not optimal to analyse this data, preventing a true scientific breakthrough. Indeed some of the most urgent questions in this research field, concerning the evolution of rare ultra-massive galaxies, may remain unsolved. As the Cosmic Dawn Center (University of Copenhagen) is collecting an unprecedented large sample of photometric and spectroscopic data, this is the best time to devise new tools for a full exploitation of such unique observations. The proposed project will devise an original machine learning software to efficiently extract information from the Cosmic Dawn Survey database, and an advanced statistical analysis will result in unprecedented demographics (e.g., stellar mass function) of high redshift (z>3), massive (>5e10 Msol) galaxies. By interpreting these measurements through theoretical models, the project will shed light on the physical mechanisms driving star formation in such extreme galaxies, which are thought to contain most of the stellar mass in the early universe. Besides the unparalleled data set, the expertise of S. Toft (host supervisor) and the other members of the Cosmic Dawn Center will be crucial to achieve these goals.

Mots clés : early universe, galaxy statistics, stellar mass assembly, dark matter haloes

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 207312.0 €
Projet NANOFI (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

An important challenge for quantum information networks is the development of efficient quantum memories and sources of single-photons. A promising category of such devices is based on ensembles of neutral atoms. The motivation comes from the fact that collective effects related to large number of atoms make it much easier in principle to achieve a strong and controllable coupling between the medium and the light. The present project aims at performing such experiments based on an ensemble of cold atoms trapped in the vicinity of a nanofiber, which will enable to obtain a larger optical thickness, a better coupling between collective excitations and light modes and thus a larger efficiency than previous ensemble-based implementations.

Mots clés : quantum memories, single photon sources, quantum information science, quantum cryptography, quantum communication, nanofiber, neutral atoms, entanglement

Participants :
- Sorbonne Université (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 185076.0 €
Projet Fluidblasto (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

An important morphogenetic event of mammalian embryogenesis is the formation of a blastocyst with a fluid-filled cavity, blastocoel, and the establishment of three cell types essential for implantation. Morphogenesis of the blastocyst begins with the emergence of multiple nascent cavities, which progressively coalesce to form one cavity segregating the cavity-facing primitive endoderm from the epiblast within the inner cell mass. While cell-to-cell gene expression heterogeneity is well characterised during this lineage specification, little is known about the physical principles governing self-organized blastocyst morphogenesis and patterning. In particular, changes in fluid pressure, cell shape and polarity during blastocyst formation remain uncharacterized. In this project, I will study the roles of fluid cavities in coordinating tissue mechanics, polarity and lineage specification. I will establish a novel micropressure technique to quantify the growth of luminal pressure during blastocyst development. Combining micropipette aspiration with high-resolution live-embryo imaging, I will characterize the impact of fluid pressure on trophectoderm fate specification through dynamic changes in cell shape and adhesion, and cytoskeletal remodeling. To assess the impact of fluid pressure on inner cell mass, I will study if cavity expansion induces apical polarisation and enhances primitive endoderm differentiation in cavity-facing cells. Combining laser ablation with light-sheet microscopy, we will build a spatio-temporal map of intercellular forces in vivo during blastocyst development. We will further manipulate the cavity size to study if fluid pressure is functionally required and sufficient for driving lineage segregation. This interdisciplinary and quantitative study will establish the novel role of fluid cavities and elucidate their interplay with biochemical signaling within the multi-cellular self-organization process.

Mots clés : self organization, mouse blastocyst, tissue mechanics, fluid pressure, lineage segregation, polarity

Participants :
- European Molecular Biology Laboratory (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 171460.8 €
Projet MICROS (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

An increasing number of people suffer cardiovascular diseases and experience myocardial infarction (MI). The subsequent heart remodeling is characterized by weaker contractility, hypertrophy and lethal arrhythmias. The poorly-understood underlying mechanism is related to calcium (Ca2+) mishandling in cardiomyocytes and oxidative stress. To date, most of the studies described global cellular processes and were unable to propose efficient therapies. This work will decipher the structural and functional local organization of reactive oxygen species (ROS) at Ca2+ signaling microdomains: at the vicinity of ryanodine receptors (RyR). Our knowledge is drastically hampered by the lack of local, quantitative and time-resolved ROS probes. We will thus combine the host laboratory competence in cardiac signaling and physiology, and the applicant expertise in ROS luminescent probes in order to quantify the RyR signaling domains remodeling through: (1) the measurement of local ROS production dynamics by NOX2 complexes, and (2) the imaging of the structural remodeling of the microdomains. This research will propose specific molecular targets to better diagnose and potentially reverse heart remodeling after infarction, contributing thus to solve a major public health issue in Europe. The experienced researcher (ER) will gain new technical and conceptual skills in physiology which will reinforce her multi-disciplinary profile and qualify her to lead, in a close future, her independent research activity.

Mots clés : ros signaling, ca signaling, myocardial infraction, luminescent nanoprobe

Participants :
- KU Leuven (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 160800.0 €
Projet OPTBIOMAN (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

An inter-disciplinary modelling and optimization framework will be developed to economically optimize biomanufacturing decision under high process variability, failure risks, and expensive operating costs. New stochastic models will be developed to link the underlying biological and chemical dynamics of the biomanufacturing processes (cell-level dynamics) with the financial trade-offs in terms of yield, quality, operating costs, and failure risks (manufacturing system-level dynamics). In particular, the research project will model and analyze the economics of the upstream fermentation and downstream purification operations. Novel approximations and heuristics will be developed based on the unique features of the problem setting in order to solve large size problems encountered in industry practices. Optimal (near-optimal) operating policies will be theoretically and numerically analyzed for both upstream fermentation and downstream chromatography operating decisions. The framework will provide timely and effective tools and models to economically optimize biomanufacturing decisions. A solid inter-disciplinary research foundation will be built combining the knowledge from the biological and chemical engineering, stochastic control, reliability theory, and manufacturing systems engineering. This research project will expand and strengthen the industry network of the OPAC group at Eindhoven University of Technology towards the emerging biomanufacturing industry in the Europe. The tools and models developed in this project will be relevant to the European industry practices, and will benefit the European society by making these therapeutic drugs more accessible in the future.

Mots clés : biomanufacturing, stochastic modeling, process economics, optimization

Participants :
- Eindhoven University of Technology (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 177598.8 €
Projet EVER (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Animal venom is a remarkable example of convergent evolutionary novelty - it has independently evolved across all phyla of the animal kingdom to subdue prey and predators. To produce and deliver this potent biochemical weapon, venomous animals possess specialized anatomical structures which emerge from different developmental tissues in the various lineages. How animals have repeatedly evolved this key adaptive trait is unknown. The recent omics revolution has generated an explosion of venom-gland transcriptomes mainly for biodiscovery. However, the mechanisms underlying the emergence and regulatory evolution of venom have not been investigated. In this ambitious and ground-breaking project, I will use a hierarchical approach and large-scale comparative transcriptomic analyses to shed light on the following open questions: Q1) To what extent is the independent evolution of novel adaptive traits associated with convergence in transcriptome evolution? Q2) Which molecular processes contribute to the evolution of these innovative traits? Q3) To what extent does the expression pattern of new specialized cell types overlap the original tissue from which they develop? I will answer Q1 by comparing non-homologous venom-gland transcriptomes across the major lineages of the animal kingdom. I will answer Q2 by focusing on one lineage (Neogastropoda) and comparing the venom-gland with homologous, non-venomous organs. Finally, I will answer Q3 by analysing gene expression patterns between structurally and functionally different cell types within the venom-gland. The success of this project is ensured by the integration in top hosting bioinformatics groups at the Université de Lausanne and collaboration with leading experts in cone snail evolution. This project will provide intensive training which is crucial for restarting my research career and establishing myself as a pioneer and leader in a new research area, venom evo-devo.

Mots clés : evolution, evolutionary biology, bioinformatics, regulatory network

Participants :
- University of Lausanne (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 286724.16 €
Projet OntoPerson (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Animalism and the so-called simple view, among many others, constitute competing theories of personal identity. According to the first, persons are biologically individuated animals whose persistence through time consists of some kind of biological continuity. According to the latter, there are no criteria of personal identity: no sort of continuity is both necessary and sufficient for a person to survive. Although these theories usually stand in radical opposition, there is, nevertheless, room for a possible link between them. The main objective of this project is to demonstrate that under certain assumptions both theories are reconcilable and that the combined position has measurable theoretical and practical advantages over existing approaches. In this project I intend to develop a new approach to human persons, according to which it would be possible, first, to reconcile some thus far contradictory conceptions of the human person and personal identity, second, to solve some of the interpretational difficulties concerning issues related to personal identity and constitution, third, to give a coherent and uncontroversial philosophical two-fold picture of human beings, enabling rational decision-making in the areas that are of practical importance. The consecutive research stages of the project are: (1) an analysis of various forms of the so-called simple view with regard to personal identity; an analysis of the criteria of personhood and of the ontological structure of persons; an examination whether the term "person" is a sortal term (resp. whether persons comprise a natural kind); (2) a reconstruction of differences between many versions of animalism; a reconciliation of a specific form of the simple view with a chosen version of animalism; (3) a verification whether the obtained results have any bearing on the debates in philosophical thanatology and bioethics.

Mots clés : ontology, identity, persistence, person, animal, death

Participants :
- University of Augsburg (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 85730.4 €
Projet RETICULUS (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Animals have a diverse set of behaviors that are triggered by specific sensory stimuli, such as motion or looming. In the visual system, this process begins in the retina where the visual scene is divided into 20 parallel information channels before reaching the brain. The superior colliculus is one of the main recipients of retinal output and it mediates tractable visually-guided behaviors such as eye movement, orienting or escaping behaviors. However, it remains unknown how visual signals from individual retinal ganglion cell types are processed by neurons in the superior colliculus to achieve specific computations relevant to behaviors. To answer these questions, I will use transgenic mouse lines recently identified by the host laboratory, in which specific types of retino-recipient neurons of the superior colliculus are labeled with Cre recombinase. First, I will characterize the response properties of Cre-labeled individual cell types using in vivo two-photon calcium imaging during visual stimulation. Next, I will initiate calcium sensor-functionalyzed trans-synaptic viral tracing from Cre-labeled collicular cell types, and perform two-photon calcium imaging of labeled presynaptic retinal ganglion cells and starter collicular neurons. With this approach I will relate the activity of neurons to the activity of connected neuronal networks, and evaluate the degree of convergence and divergence in retino-collicular connectivity. By linking cell types, circuits and computations, this work will provide mechanistic insight into the circuit basis for parallel processing of visual information and various visual functions in the healthy system, while possibly disclosing novel therapeutic targets for visual motor diseases.

Mots clés : superior colliculus, retinal ganglion cells, visual processing, visual circuits, trans synaptic viral circuit tracing, two photon calcium imaging

Participants :
- Aarhus University (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 200194.8 €