Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet AudiLearn (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Interpretation of external stimuli is essential for us to interact properly with our environment. In this context, sound is a major sensory information that takes part in social interaction but also alerts of dangers. Auditory stimuli are integrated by stereotyped neuronal circuits where inhibitory neurons play a key regulatory role. These circuits can be modulated for example by learning which allow a better reaction in sensory-guided behaviors. It has been recently suggested that higher-order brain areas feedbacks onto primary sensory cortices are essential in these learning processes as they modulate primary sensory circuits. Yet, less is known about long-range circuits involved in learning processes which allows the animal to respond more precisely to auditory stimuli. The objectif of AudiLearn is to disentangle how higher-order brain areas influence auditory learning. My working hypothesis is that long-range modulation of auditory cortex neurons is reinforced during learning in order to increase their response accuracy. Therefore, AudiLearn aims at (i) identifying neuronal subpopulations of the primary auditory cortex that present changes of activity with learning using in-vivo electrophysiological recordings of neuronal activity in the auditory cortex and optogenetics during an auditory discrimination task in mice, (ii) detect long-range projections onto these neurons using rabies-virus based monosynaptic retrograde tracing and finally (iii) modulate these long-range presynaptic neurons with optogenetics to decipher their role in modulating sensory coding during the auditory learning process. This project will bring a novel insight in auditory coding by identifying long-range modulators of the primary auditory cortex. More generally, it will increase our understanding of the learning-processes that occur in sensory cortices which can be impaired in pathological conditions such as in tinnitus, autism or schizophrenia.

Mots clés : auditory cortex, sensory learning, interneurons, optogenetics, rabies virus tracing, neuronal circuits, network modulation, gaba, sensory coding

Participants :
- University of Basel (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 191149.44 €
Projet SURFInG (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Interspecific hybridization and genome doubling (allopolyploidy) are key factors in plant adaptation and speciation. These intriguing genomic processes cause extensive structural rearrangements and reprogramming of functional regulatory pathways inherited from parental species. Furthermore, hybrid species have shown broad phenotypic diversity. However, mechanisms responsible for genome stabilization after allopolyploidy remain poorly understood. The aim of my project is to provide an interdisciplinary overview of the effects of polyploidy on structural and functional dynamics in a major crop, oilseed rape (Brassica napus). This polyploid species is an excellent system to unravel the long-term and immediate evolutionary effects of ancient and recent polyploid events. In my project, I will use a novel approach that combines (epi)genomics and transcriptomics in phenotypically contrasting polyploids to investigate the role of structural and (epi)genetic regulation in genome stabilization. This work includes, amongst others, the transfer of knowledge to the host lab of cutting-edge molecular and in silico DNA methylation analysis methods. More specifically, I will determine the effects of structural and functional dynamics on B. napus (1) meiotic behavior and fertility, (2) gene expression and (3) glucosinolate content. My findings will open new avenues for using standing variation to modify and ultimately enhance agronomic traits. I have become a recognized evolutionary biologist working at the interface of ecology, genomics and molecular biology. From the expertise of the host lab and availability of technical platforms in situ, I will not only get acquainted with cytogenetics and metabolomics, but will increase my expertise in comparative genomics and in high throughput genotyping analyses. I will also extend my network towards the private sector and be integrated into a well-established European community, positioning me on track to succeed academically in France.

Mots clés : oilseed rape, polyploidy, genome dynamics, duplicated genes, fertility, glucosinolates

Participants :
- Institut national de recherche pour l'agriculture, l'alimentation et l'environnement (France) — Coordinator, beneficiary, Recherche, subvention : 185076.0 €
Projet NanoBioCar (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Intertidal and shallow subtidal zones are key areas for biochemical transformations, and particularly they play a crucial zone in the carbon cycle. In soft-bottom areas, most primary production is performed by photosynthetic microorganisms organised in biofilms, and called microphytobenthos. The organic matter they produce is rapidly respired by bacteria or consumed by higher trophic levels. Together, microphytobenthos and bacteria realise most carbon transformation in these areas, and are therefore important groups to study in a view to understand carbon cycling in coastal zones. Coastal areas are currently under influence of numerous stressors linked to anthropogenic effects. The impacts of ‘well established’ pollutants, e.g. metals, oils, nitrogen, are fairly well understood; however there is now evidence that new compounds, products of advanced technology, have the potential to disrupt the environment. The aim of this project is to understand how a recently developed family of compounds, namely nanoparticles (NPs), influences the development of biofilms and their impact on the carbon cycle. NP concentrations are increasing dramatically in the environment, but their effect on organisms and ecosystems is currently poorly described. Yet, genotoxic and cytotoxic effects of NPs have been demonstrated, including on microorganisms. In this project, laboratory and field experiments will be performed to characterise the effects of NPs on microphytobenthos and bacteria, on their trophic interactions and on their roles in carbon and nutrient cycles. Two common types of NPs will be tested in a wide range of environmental conditions, to decipher in which conditions NPs are more or less harmful to organisms and processes. Such understanding will allow developing strategies to reduce the impacts of NPs and will be beneficial to environment and human well-being in EU and elsewhere.

Mots clés : nanoparticles, biofilms, carbon cycle, coastal area, microphytobenthos, photosynthesis

Participants :
- University of Essex (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet EPiCC (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Intrahepatic cholangiocarcinoma (iCC) is an aggressive malignancy of the biliary tract with escalating rates among both sexes in EU. Patients survive less than one year from diagnosis due to limited treatments and innate chemoresistance. Genomic analyses have identified recurrent mutations in epigenetic regulators in iCC. Malfunction of such genes has genome-wide consequences for epigenome-remodeling and transcriptome homeostasis, though this remains largely uncharacterized in iCC. Further, the extent to which iCC survival depends on these epigenetic alterations has not been determined. Clarification of these dependencies on epigenetic alterations, which unlike mutations are reversible, is crucial for the development of precision epigenome-targeted therapies for this aggressive disease. Using patient-derived cell lines (PDCLs), I propose to characterize iCC epigenetic survival dependencies to define the functional role(s) of key epigenetic regulators and ensuant epigenome remodeling, in turn identifying putative novel therapeutic targets. To achieve this, I have divided my EPiCC proposal in 2 specific aims: 1.Identify iCC-selective functional survival dependencies by state-of-the-art CRISPR/Cas9 screening. 2.Characterize the anti-neoplastic cellular and (epi)genomic consequences induced by the top epigenome regulator loss. Through integrating novel comprehensive approaches in iCC (CRISPR/Cas9 screening, R-loop mapping) with robust patient models (primary cells, omics from patient samples), I will provide novel insight into the epigenetic landscape of iCC and identify potential targets for future development of epigenetic-based precision medicine. This study will be supervised by Dr. Andersen, leading expert in the field of hepatobiliary cancers and translational genomics research. Therefore, EPiCC will provide me with new scientific expertise (both technical and transferable skills), a broader network and open new research avenues to follow up in my career.

Mots clés : cholangiocarcinoma, translational epigenomics, epigenetic therapy, r loops

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

Intrahepatic cholangiocarcinoma (iCCA) is the second primary malignancy of the liver with few therapeutic options, late diagnosis, chemotherapy resistance and dismal prognosis. iCCA incidence and mortality increased worldwide in the last decades, linked to the rise of risk factors including non-alcoholic steatohepatitis. iCCA is a highly heterogeneous tumor characterized by a complex and dynamic tumor microenvironment (TME) where stromal cells coexist with cancer and cancer stem cells (CSC). CSCs are a heterogeneous subpopulation of cancer cells capable of tumor initiation, malignant growth and responsible for chemoresistance. The main objective of the “SteMiCCA” project is to identify and target the unexplored CSC-TME interactions in iCCA, aimed to better understand the complex biology and to identify new therapeutic targets for this deadly disease. To achieve this objective, an interdisciplinary approach including in vitro (spheroids and organoids from human and mouse) and in vivo (ICC-models, subcutaneous and xenograft tumor induction) systems; high throughput transcriptomics (scRNA-Seq and RNA-Seq) and bioinformatics will be employed. Considering my strong background and experience in iCCA and TME, and the host institution’s well-recognized expertise in stem cell biology and liver cell plasticity, this proposal envisions a successful reciprocal transfer of knowledge. Moreover, this fellowship will allow me to gain expertise in supervision, intellectual property management, research funding and proposal writing, with the main goal to acquire more competences and reach professional maturity to start my own research line in iCCA. This will also be a first step to strengthen my network and start contributing to European actions such as ESCALON PROJECT 825510 and EURO-CHOLANGIO-NET, created to boost multidisciplinary studies with interest in basic, translational and clinical research in the field of CCA.

Mots clés : intrahepatic cholangiocarcinoma, cancer stem cell, tumor microenvironment, cell heterogeneity, ligand receptor interaction, chemoresistance, target therapy

Participants :
- Fundació Clínic per a la Recerca Biomèdica (Espagne) — Coordinator, beneficiary, Recherche, subvention : 172932.48 €
Projet StressRhomboid (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Intramembrane proteolysis is increasingly understood to control many cellular processes but we still know little about the role of most intramembrane proteases. The major roadblock is the lack of a robust method of protease substrate discovery. In this action, I focus on RHBDL4, a poorly understood but highly conserved member of the rhomboid intramembrane serine protease family, which participates in ER associated degradation (ERAD), apoptosis and exocytosis, and which has been frequently implicated in cancer growth and metastasis. My three objectives are to establish a systematic approach to trapping and identifying rhomboid substrates; to use this to discover the substrates of human RHBDL4; and to explore the mechanism of how RHBDL4 participates in ER quality control. Matthew Freeman's group discovered rhomboids and is a leader in the field. I will also collaborate with Jason Chin in Cambridge, who has pioneered the use of genetically encoded unnatural amino acids (UAAs) to engineer proteins. I will adapt a technique recently published by the Chin lab for use in living cells. Using a cross-linking UAA analogue of the catalytic serine in RHBDL4, I will achieve unprecedented specificity and efficiency of substrate capture. I will thus covalently capture RHBDL4 substrates, which will then be identified by mass spectrometry. Hits will be functionally validated and, using a range of experimental conditions, I will distinguish substrates involved in ERAD from substrates cleaved in other RHBDL4-dependent processes. By establishing the first systematic assay for rhomboid substrates and investigating the role of RHBDL4 in ER quality control, I will pioneer a general approach to intramembrane protease substrate discovery; gain broader understanding of how RHBDL4 contributes to cellular quality control; and finally reveal pathophysiological roles of this human protein, thereby guiding possible future therapeutic targeting.

Mots clés : serine protease rhomboid  intramembrane protease  er associated degradation substrate capture rhbdl4

Participants :
- University of Oxford (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €
Projet EpiNKT (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Invariant Natural Killer T (iNKT) cells are a heterogeneous T lymphocyte population that possess innate-like characteristics and contribute to host defense against pathogens. Due to their powerful effector properties, iNKT cells are targeted for immunotherapeutic and vaccination strategies. Their effector programs are acquired during thymic development, prior to microbial exposure, and are polarized into three distinct populations, similar to CD4 Th1, Th2 and Th17 lineages. Specification and subsequent polarization of the NKT lineage is regulated by the balance between the E protein family of transcription factors (TF) and their inhibitors, the ID proteins, which is pivotal in the bifurcation of adaptive and innate lymphoid lineages and is associated with human lymphomas. This application aims at defining the mechanisms by which the E/ID ratio enables the effector properties of innate-like T cells. We hypothesize that the E/ID pathway directly or indirectly regulates critical TFs and chromatin regulators that separately or in combination activate different arms of this effector program. This hypothesis will be tested through the following specific aims: 1) Determine target genes bound by E proteins, 2) Determine the epigenetic chromatin states and 3) Determine the role of chromatin modifiers in developing iNKT cells. While each aim can be accomplished independently, the data will be integrated to form gene regulatory networks that control the innate-like effector programs. The proposal is innovative because it explores the novel idea that the activity thresholds of a single TF dictate distinct cellular fates, while enhancing our understanding on lymphocyte effector programs and link specific chromatin regulators to these programs. The fellowship is rewarding, because the Applicant will gain knowledge in the implementation of high-throughput technologies to study the interplay between TFs-chromatin regulators-chromatin architecture in lymphocyte differentiation.

Mots clés : innate lymphocytes, id proteins, development, transcription factors, epigenetics

Participants :
- Alexander Fleming Biomedical Sciences Research Center (Grèce) — Coordinator, beneficiary, Recherche, subvention : 164653.2 €
Projet INVASOMICS (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Environment and Geosciences
Statut du projet : SIGNED

Invasive species are a major constituent of global change, threaten local biodiversity, ecosystem services, and cause serious economic damage. Invasion science has tried to discern the factors that determine whether a non-native population will become invasive or not. Invasive populations are usually depleted in genetic diversity, creating the so-called 'invasion paradox' because traditional perspectives consider high genetic variation to be crucial for rapid adaptation to novel environments. Recent theoretical advances trying to solve this paradox propose that contemporary pre-adaptation to human-altered habitats within the native range or during the transport stage in the introduction can promote invasions. If this is true, introduced populations will exhibit increased adaptive tolerance to a stressor associated with transport, e.g. eutrophication, contributing to their success in the recipient environment. The aim of this project is to understand adaptive mechanisms that promote invasion success in widespread invasive freshwater vertebrate and invertebrate species. I will study the phenotypic differentiation of wild populations of the eastern mosquitofish in an eutrophication gradient, complemented with laboratory ecotoxicology experiments, both in the native (Florida) and invasive (Spain) ranges of the model species. This intraspecific comparison will be supported by the interspecific study of 3 sympatric freshwater amphipod species in Germany to assess potential competitive shifts in the invasive ones stemming from higher tolerances to eutrophication. Including natural populations with such particularly well described invasion histories will show why some populations become invaders and others do not. Current developments in molecular genetics , e.g. ‘-omics’, give an excellent precise tool to investigate the links between the disciplines of evolutionary biology, ecotoxicology, and invasions science and help elucidate the paradox.

Mots clés : invasive species

Participants :
- State University System of Florida (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Goethe University Frankfurt (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 246669.12 €
Projet SexSelec_Invasion (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Invasive species can have dramatic consequences on the receiving ecosystem and on human activities. At the same time, invasion episodes offer a rare opportunity to observe evolution in action and study adaptation. Understanding the cornerstone role of sexual selection during adaptation can open an avenue of strategies to fight against pest species. During invasion, novel environmental conditions and rapid changes in the genetic composition of populations are expected to influence the dynamics of sexual selection. However, neither theory nor data clearly predict whether sexual selection would be reinforced or hampered during an invasive episode. Understanding the subtle consequences of invasion on sexual selection is crucial, as mating strategies provide tools to fight against pest species. The Sterile Insect Technique (SIT) successfully eliminated several pest species, limiting side-effects on the ecosystem compared to traditional techniques such as pesticides. In this project, I develop a series of experiments combining artificial selection experiments with large scale phenotyping to investigate the dynamics of sexual selection during invasion and test the potential to exploit mating strategies to control pest populations in an evolutionary sustainable way. As a model species, I will use Drosophila suzukii, a champion of invasion that colonised several continents and islands in the last decades. Because D. suzukii feeds and oviposits on close-to-be-marketed fruits, it causes considerable economic losses and the situation requires rapid action. The results of the project will provide both a fundamental understanding of the dynamics of sexual selection during invasion, and essential information for the development of sustainable, environment friendly methods to fight pest species, in particular D. suzukii.

Mots clés : sexual selection, invasion, invasive species, pest, artificial selection

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 173076.0 €
Projet OPTICS (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Ionic conducting materials form the basis of solid oxide fuel cells, solid oxide electrolyser cells, and batteries, which form a key component of the EU Energy 2050 long-term strategy. There is a need to develop faster ionic conductors, however progress has been slow. Recently, several studies have demonstrated photo-enhanced iodine-ion diffusion as well as suggested interactions between photons and oxygen-ion defects in oxide materials may be possible. The proposed research plan, OPTICS, aims to address the question: Can changes in ion transport be enhanced in technologically relevant ionically conducting oxides (O-ion, H-ion, and Li-ion) by light illumination? There are challenges in studying these effects using conventional methods. Namely, absorption only occurring at the surface in thick samples, artefacts in conductivity measurements stemming from photocurrents and electrode effects, and difficulties understanding the mechanisms due to the indirect nature of photon-ion interactions. In OPTICS, these challenges will be overcome employing isotopic tracer diffusion measurements on epitaxial thin films carried out in tandem with atomistic and continuum simulations to identify the underlying mechanisms. Combining the Host’s (Prof. Roger De Souza) expertise in tracer diffusion and atomistic modelling with the Applicants experience with optical measurements on epitaxial films, photo-enhanced ionic diffusion will be studied experimentally and computationally in the bulk, at surfaces, and at interfaces of nanostructured materials. Light-enhanced ionic transport has the potential, though OPTICS, to lead to substantial improvements in technologically relevant ionic conductors leading to a new class of photo-ionic fuel cells, electrolysers, and batteries.

Mots clés : ionic conductors, tracer diffusion, epitaxial films, nanostructured films, continuum modelling, atomistic, modelling, above band gap radiation, surfaces, interfaces, energy conversion and storage

Participants :
- RWTH Aachen University (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 162806.4 €