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Obesity has become a global epidemic and is one the most significant public health challenges of the 21st century. In obesity, chronic low-grade inflammation is thought to alter adipose tissue functions, linking obesity to its numerous co-morbidities, as insulin resistance, type-2 diabetes and cardiovascular diseases. The obese adipose tissue is a site of multiple and overlapping mechanisms that operate at different levels to promote inflammation, including immune cells infiltration and up-regulation of pro-inflammatory signalling pathways and gene expression. These processes are the focus of intense research interest, but remain to be fully deciphered in the adipose tissue. In this context, the overall aim of my project is to investigate the mechanistic control of inflammation at the transcriptional level, specifically in human adipose tissue. I and others recently proposed a new concept related to the control of inflammatory gene transcription, through the NCOR/SMRT co-repressor complexes. I have discovered that the GPS2 subunit of NCOR/SMRT complexes is required for repression of inflammatory genes in hepatocytes and macrophages. This led us to hypothesize that NCOR/SMRT complexes contribute to the regulation of obesity-induced inflammation in adipose tissue. To test this hypothesis, my project aims at deciphering the molecular actions and physiological functions of the NCOR/SMRT co-repressor complexes in adipose tissue. To my knowledge, this novel molecular pathway has never been investigated so far in human or mouse adipose tissue. My major focus will be to i) identify the subset of genes controlled by NCOR, SMRT and GPS2 and their associated epigenetic code in human adipose cells, ii) characterize the metabolic and inflammatory consequences of GPS2 adipose-specific depletion in genetically modified mice and iii) evaluate the relevance of enhancing NCOR/SMRT co-repressor complexes activity to control inflammation in adipose tissue. Overall this project will benefit the Research Community, by improving our basic understanding of the transcriptional control governing obesity-induced inflammation. Since adipose tissue inflammation is recognized as a major pathogenic process in obesity linked metabolic complications, including type 2 diabetes, my research project could lead to define new therapeutic strategies targeting the NCOR/SMRT complexes to ameliorate inflammatory and metabolic status in obese subjects.

Wastewater represents a massive amount of water (13 to 15 million m3 / day in France) that could be used as a potentially worthwhile resource, regardless of seasonal droughts. However, wastewater treatment plants are currently not able to achieve in a cost-effective way a sufficient water quality for its reuse as a resource. Therefore, the development of efficient strategies for further eliminating micropollutants and improving the microbiological quality of water is required in order to meet the European Framework Directive on Water and to overcome future water shortages. In this context, REMemBer is an applied research project that aims to develop a sustainable wastewater treatment technology allowing: (i) the implementation of an innovative compact solution combining both secondary and tertiary treatments within the same process (ii) the improvement of the chemical and microbiological quality of treated water, (iii) the possibility to recycle the treated water, and (iv) a lower footprint and consumption of energy/chemicals . The project is based on the combination of the advantages of membrane bioreactors (MBR) and electrochemical processes in a single innovative unit while overcoming the main disadvantages of both technologies (membrane fouling, mass transfer limitations, etc.). The novelty of the REMemBer project lies in the use of reactive electrochemical membranes (REM) as flow-through electrodes. REM have already been synthesized and showed a strong potential to reduce limitations related to diffusion of pollutants from the bulk to the electrode surface. Based on these promising results, the scientific challenges that will be addressed in this project aim at reaching a new milestone through the implementation of REM in a one-pot process where both the biomass separation and the tertiary treatment would be achieved in a single reactor: a Reactive Electrochemical Membrane Bioreactor (RE-MBR). The objectives are: (i) to favor the electro-oxidation of micropollutants owing to the convection-enhanced mass transport of pollutants, (ii) to improve the disinfection by both electro-oxidation and local pH conditions and (iii) to control membrane fouling. The main scientific and technological challenges for the implementation of a RE-MBR at industrial scale lie in: (i) the development of reactive electrochemical ultrafiltration membranes from microfiltration membranes currently commercially available, (ii) the understanding of (electro)chemical, physical and biological mechanisms at the electrode-liquid interface, which are only slightly described in the literature for this application and (iii) the design and validation of an electrochemical cell allowing optimal control of RE-MBR effectiveness and scale-up for an industrial application. The REMemBer project aims to address these challenges by developing a multi-scale approach combining multidisciplinary experimental analyzes and modeling. The scientific program of the project is divided into five main scientific and technological tasks: REM elaboration, characterization and optimization (WP1); understanding of the mechanisms at the REM-liquid interface (WP2); assessment of global performances and effectiveness of the process at lab-scale (WP3); multi-scale modelling (WP4); development of a demonstrator for technical, economic and environmental analyses (WP5). The project brings together two university laboratories LGE (Université Gustave Eiffel) and IEM (Université Montpellier), an applied research institute (INRAE-PROSE), SIAAP (the Greater Paris Sanitation Authority (public industrial company)) and a small company specialized in development of innovative processes and technology transfer (FIRMUS).

L'objectif du présent projet est de développer une méthodologie de création, d'analyse et de modélisation de nouvelles microstructures, pour des métaux et alliages variés, permettant d'un point de vue fondamental d'explorer plus à fond les liens entre transformation des matériaux et état microstructural. Une telle méthodologie sera à terme un outil puissant pour associer certaines familles de matériaux à des procédés qui ne sont pas utilisés pour celles-ci, permettant d'obtenir des microstructures innovantes aux propriétés inédites. Ce projet comprend trois grandes étapes :(i) le développement d'un laminoir pilote, outil de création de microstructures, suffisamment souple pour être utilisable sur un grand nombre d'alliages et permettre l'exploration de schémas thermomécaniques complexes (incluant notamment le laminage asymétrique, le laminage croisé, le co-laminage et l'exploration d'une vaste gamme de températures de déformation) ; il sera ainsi possible d'activer, de façon simultanée ou non, les principaux mécanismes de structuration qui sont la fragmentation de grains au cours de déformations sévères, la restauration, la recristallisation continue ou discontinue et la transformation de phases ;(ii) la modélisation de ces mécanismes élémentaires et le développement et la validation des modèles d'évolution microstructurale existant déjà dans nos laboratoires,(iii) à plus long terme, le calcul d'un ensemble de propriétés mécaniques, électriques et magnétiques permettant d'évaluer ainsi quantitativement l'effet de la microstructure créée.Grâce au regroupement de 4 laboratoires possédant des compétences complémentaires et pluridisciplinaires dans les domaines technologique, mécanique et métallurgique ainsi qu'une forte pratique des outils numériques et expérimentaux nécessaires à la caractérisation et la modélisation des microstructures observées, les principaux résultats attendus sont, outre le développement du laminoir pilote :- Une exploration de microstructures inaccessibles jusqu'à présent ;- Une caractérisation systématique des plus intéressantes et/ou inédites d'entre elles, en fonction des conditions de laminage. - A terme, une meilleure compréhension de la formation de ces microstructures. L'objectif à long terme est de créer ainsi un pôle de compétences sur le développement de microstructures dites « innovantes », c'est-à-dire capables de permettre une amélioration significative des propriétés des matériaux ; le laminoir pilote, créé à cette occasion, pourra par la suite être mis à disposition des deux fédérations CNRS représentées par les 4 laboratoires (F2MSP et FédéRAMS), d'entreprises partenaires (grands groupes et PME), de la PFT « Mécanique, Matériaux et Productique » récemment crée dans le Nord Francilien ainsi que de filières de formation technologiques, afin d'étendre encore le domaine d'investigation de nouveaux matériaux.

Speech rate and pauses provide us with a window into the cognitive-neural and physiological-articulatory bases of the human language production system, but cross-linguistic variation in this domain remain understudied. This project fills this gap by comparative studies of spontaneously spoken language in a diverse sample of 50 languages. For this purpose, we create a multilingual reference corpus of language documentation data (DoReCo) consisting of annotations and associated audio recordings that are archived at repositories such as The Language Archive (TLA), especially from the DOBES collection. DoReCo will be built from data that are already transcribed, translated into a major language, and time-aligned at the level of discourse units with audio files. Within the current project, these data will be time-aligned at the phoneme level. We have identified at least 50 languages, from which corpora of at least 10,000 words can be included in DoReCo, and a subset of at least 30 of these, which are additionally already annotated for morpheme breaks and morpheme glosses. In DoReCo, subcorpora and annotations are treated as citable publications, provided with a permanent identifier and associated with a CC BY 4.0 license. DoReCo will have a lasting effect beyond the specific research goals of the DoReCo project, as a platform for easy access to over one million words of annotated corpus data from over 50 languages for cross-linguistic research on spoken language. This represents an unprecedented contribution to open, reproducible science regarding global linguistic diversity and cultural heritage. Both of DoReCo’s two specific research goals address the universality of constraints on human language arising from species-wide articulatory and cognitive properties: Firstly, we investigate patterns of phonetic lengthening with the aim towards establishing universal vs. language-specific patterns in (i) the degree to which different types of phonological segments undergo variation in duration (e.g. vowels vs. different types of consonants)–reflecting articulatory and perceptual constraints–and (ii) word-final lengthening as indicative of major vs. minor prosodic boundaries–reflecting cognitive constraints on planning and potentially signalling discourse units. Secondly, we investigate universal vs. language-specific patterns in the temporal distribution of morphemes regarding (i) information rate in terms of morphemes per second and (ii) the number of morphemes in inter-pausal units–both reflecting cognitive constraints on language use. The project will be carried out by an interdisciplinary team bringing together expertise on documentary linguistics, phonetics, typology, and quantitative linguistics, with strong institutional support from two leading research centres in Germany and France.

This study will evaluate the needs and provision of care for patients in the late stages of Parkinsonism and their carers in several European countries. This will done through an in-depth assessment of patients and carers, interrogation of national and regional databases, and assessment and outcome of management strategies in six European countries. We will compare the effectiveness and cost of different health and social care systems, and carry out a trial comparing assessment by a specialist with management suggestions, guidance and access to telephone advice to that of usual care. A systematic literature review of the evidence for effective management strategies, analysis of the study data, and evaluation of change in outcomes following specialist review will provide the basis for recommendations in the management of late stage Parkinsonism. In addition, the project will produce a platform for the assessment of patients with late stage Parkinsonism, their current treatment and care provision, as well as guidelines on the management of this late disease phase. The results may also provide a model for the research on better management of other chronic neurological disorders and age-related disorders in various health-care systems.

En ce début de 21ème siècle les concepts de développement durable et de Green Chemistry sont au centre de l’activité chimique et la recherche d’une haute sélectivité est la force motrice de la conception de tout nouveau procédé catalytique. Ce projet a pour objectif le développement de catalyseurs hautement sélectifs en utilisant des outils issus des nanotechnologies. Il est axé sur la synthèse contrôlée de nanoparticules métalliques (NP) par des procédés de chimie douce suivie de leur confinement dans les mésopores de nanotubes de carbone (CN) de type multi-parois produits par des méthodes de dépôt chimique en phase vapeur catalytique. Deux approches seront considérées, soit l’introduction des NP fonctionnalisées préformées, soit la synthèse des NP fonctionnalisées directement à l’intérieur des CN. Pour cette dernière approche, un effet de confinement est espéré, avec des répercussions possibles sur la morphologie des NP obtenues. La conception de ligands multifonctionnels est un aspect important du projet car ils devront 1) assurer la stabilisation des NP afin qu’elles soient monodisperses en taille et qu'elles puissent entrer dans la cavité centrale des CN, 2) posséder une terminaison en adéquation avec la surface des CN de façon à permettre le bon accrochage des NP et 3) posséder un centre ou un environnement asymétrique pour provoquer l’induction de sélectivité. Les matériaux préparés seront caractérisés finement par des méthodes de microscopie électronique et le degré de l’amplification de la sélectivité catalytique par l’effet de confinement sera évaluée par l’étude de réactions stéréo- et régiosélectives. Un système de boucles itératives sera mis en place de façon à bien cerner les relations structures activité/sélectivité.

Understanding the molecular mechanisms underlying the construction of multicellular organisms is a central question in biology that can yield key knowledge with a wide range of potential applications ranging from medicine to agriculture. In both plants and animals, the construction of the body plan commonly occurs through rhythmic addition of new segments at the tip of growing structures. However, little is known on whether and how growth contributes to the establishment of rhythmic morphogenesis and thus to the construction of complex eukaryotic organisms. In this fundamental project, we will address this question in plants using the shoot apical meristem (SAM) whose stem cell niche activity controls post-embryonic primary shoot architecture, also known as phyllotaxis, by producing rhythmically new aerial lateral organs and corresponding stem segments. We will focus our analysis on a class of key plant growth regulators, the plant hormone gibberellins (GA), and will elucidate their function in establishing the spatio-temporal dynamics of morphogenesis at the SAM trough growth regulation and in the determination of shoot architecture. While GA are known to act in the SAM and to impact the dynamics of patterning, the molecular mechanisms underlying growth regulation by GA at the SAM are entirely unknown. To dissect these mechanisms, we will develop a novel GA biosensor and reporters to characterize in details the 4D (3D + time) distribution of GA and GA signaling in the SAM using live-imaging, as well as their regulation. We will map growth patterns in the SAM and will use both pharmacological and genetic approaches to interfere inducibly with GA activity, in order to analyze the causality between GA activity and growth. Interfering with GA activity will also allow us deciphering how GA activity impacts morphogenesis dynamics and thus phyllotaxis and shoot architecture. Finally, a combination of targeted and non-targeted approaches based on protein imunoprecipitation as well as genomics approaches will allow identifying transcription factors targeted directly by GA signaling in the SAM and the downstream gene network mediating growth regulation in this tissue. The knowledge generated in this project will provide a unique multiscale vision of how growth is coordinated by GA in a plant complex tissue to ensure both stem cell niche maintenance and reiterative organogenesis and of how it contributes to building complex architectures. As GA are required throughout the life of the plant, this knowledge will have a broad impact for the understanding of plant growth. This multidisciplinary project associates two complementary partners, both from the thematic and from the methodological point of views. The team headed by Teva Vernoux (RDP, Lyon; Coordinator) is expert in hormone signaling and meristem biology and the one headed by Patrick Achard (IBMP, Strasbourg) is focused on gibberellin biology. Moreover, the laboratory in Lyon has an internationally recognized expertise in systems biology and live imaging that complements the biochemistry, cell biology and genomics expertise of the Strasbourg team. These complementarities will yield a high synergy key to the success of the project.

In the context of climate change, it appears essential to unravel the mechanisms governing abiotic stress tolerance in higher plants, in order to build predictive models and use this knowledge to assist selection and design of stress tolerant crops. We have previously uncovered remarkable adaptations in seed mitochondria, which because of the ability of seeds to survive desiccation, display impressive tolerance to abiotic stress. In particular, seed mitochondria accumulate high levels of small heat shock proteins (sHSP) and late embryogenesis abundant proteins (LEA). The sHSP are the most widespread but less conserved HSP. They contribute to the molecular chaperone network that assists protein biogenesis and homeostasis under stress conditions (sHSPs are stress inducible). In eukaryotes, mitochondrial sHSP (M-sHSP) have only been identified in plants and insects. LEA proteins are highly hydrophilic proteins, generally intrinsically disordered, which accumulate in desiccation tolerant organisms, and whose functions still remain largely enigmatic. The MITOZEN project aims at deciphering the molecular function and physiological role of the mitochondrial sHSP and LEA proteins (M-sHSP and M-LEA) in the model plant Arabidopsis thaliana. The genome of Arabidopsis harbors 17 sHSP genes (including 3 M-sHSP) and more that 50 LEA genes, among which we have recently identified 5 M-LEA genes. The molecular functions of the M-sHSP and M-LEA will be explored using biochemical and biophysical approaches to study recombinant proteins produced in Escherichia coli. Their structural features and protective activities (oligomerisation, secondary structure, chaperone activities, membrane protection) will be examined in the context of temperature stress and dehydration using a large panel of techniques and in vitro assays. The goal is to determine the potential molecular functions of the different M-sHSP and M-LEA in the context of stress tolerance (desiccation in seeds, high temperature in seeds and plants). A reverse genetics approach will be developed in Arabidopsis to explore the role of M-M-sHSPs and M-LEAs in the physiology and development of plants. Single and multiple knock-out mutant lines will be constructed, as well as overexpressors using an inducible system. Their phenotypic characterization will focus on seed development and abiotic stress tolerance of plants, including mitochondrial function. The integration of data provided by these multidisciplinary approaches (bioinformatics, biochemistry and biophysics, genetics, physiology) will shed light on the function and importance of the different M-sHSP and M-LEA in the development and stress tolerance of plants. It will also increase knowledge about molecular chaperones and in particular with respect to their yet unexplored role in the context of dehydration, and will shed novel light on the function of LEA proteins.

People tend to remember only relevant aspects of life events. Notably, fear experiences, are preserved over time but their spatial details are lost. Where does this contextual information go? Memory consolidation is a gradual process that creates a strongly wired network of brain regions that allows for the later retrieval of memories. Here, we hypothesize that this consolidated network interferes and inhibits other circuits, including the spatial representation system to allow a faster and more accurate recall of consolidated fear memories. We will (1) identify key regions of the memory network and test whether they regulate spatial representation circuits and (2) test whether the neurons encoding the spatial information during the traumatic event become silent during remote memory recall. Altogether, this project will significantly further our understanding of how networks are reconfigured during the consolidation of fear memories.

The rise of a vast family of two-dimensional (2D) crystals, with unique electronic and optical properties, has opened exciting perspectives for “van der Waals heterostructures”. The latter are only a few atoms thick and exhibit new properties and functionalities that cannot be achieved using bulk crystals. Indeed, 2D crystals feature exposed electron gases, which properties are dramatically influenced by non-covalent coupling to low-dimensional adsorbates. So far, most endeavors have focused on heterostructures based on graphene, boron nitride, and transition metal dichalcogenides (MX2, with M=Mo, W and X= S, Se, Te). In particular, graphene, as a 2D semimetal with extremely high carrier mobility but no bandgap and “monolayer” MX2, as direct bandgap semiconductors with good carrier mobility, are highly promising building blocks for optoelectronic devices (OEDs). Besides, 2D crystals are naturally suited for lateral geometries and can be more easily integrated in OEDs than 0D and 1D nanostructures. Yet, the fabrication of high-quality heterostructures based on graphene and MX2 relies on sophisticated processes, which offer limited scalability and device engineering possibilities. At the same time, a breakthrough has been achieved in the controlled colloidal synthesis of layered semiconductors, such as core only, core-shell and core-crown 2D nanoplatelets (NPL, or quantum wells) based on metal chalcogenides (CdSe, CdS, CdTe,…). NPL are excellent light-absorbers and emitters. Their thickness, which directly defines their electronic structure and peak emission energy, is controlled at the monolayer level, while their lateral dimensions can attain the µm range. In addition, NPL surface chemistry can be efficiently tailored. Importantly, highly homogeneous ensembles of NPL, with high structural quality can be synthesized, processed and integrated into OEDs. Nevertheless, electron transport in NPL films remains driven by hopping processes, leading to limited carrier mobility. It therefore seems natural to combine i) graphene and MX2, as semimetallic or semiconducting channels with good transport properties and ii) NPL, as a tunable active materials, into novel hybrid 2-dimensionnal heterostructures (H2DH) and OEDs. The performance of such devices is governed and often limited by band alignment, interactions with the underlying substrate, and crucially, short range phenomena such as charge separation, charge transfer and Förster resonant energy transfer (FRET). FRET is a “dipole-dipole”, non-radiative coupling phenomenon, involving a photoexcited donor and an acceptor, which absorption spectrum overlaps with the emission spectrum of the donor. FRET between a photoexcited NP and a graphene or MX2 layer may bypass direct charge transfer processes, which could lead to an electrical current, useful for optoelectronic applications. FRET may be seen as an efficient way to harvest and funnel energy from photoexcited donors, which is of major interest for photodetection. However, in the absence of a charge separation mechanism, the energy transferred as electronic excitations will be rapidly dissipated into heat. H2DH offer a natural and elegant platform to address these issues and to uncover new regimes of electron transport, charge separation, photoconductivity, photodetection and electrically-controlled luminescence. For our project, we will grow high quality 2D materials (graphene, MX2, and NPL) that will be assembled intro electrically contacted H2DH, using original fabrication methods based on resist-free processing and electrochemical gating. We will investigate the fundamentals of charge and energy transfer in NPL-graphene and NPL-MX2 H2DH using a complementary set of optical and electron spectroscopy studies, as well as optoelectronic measurements. This fundamental work will guide a more applied, yet equally important effort towards the development and extensive study of a new class of phototransistors based on H2DH.