Ce projet a pour objectif la mise au point de catalyseurs de polymérisation originaux fonctionnant à l'intérieur d'une cavité moléculaire. Le déroulement d'une réaction catalytique dans un espace confiné de type cavitand pourrait non seulement aboutir à des sélectivités de forme, mais encore conduire à la mise au point de nouveaux catalyseurs de polymérisation solubles dans l'eau. L'objectif visé constitue tout d'abord un défi sur le plan fondamental (il n'existe en effet, à l'heure actuelle, qu'un seul système catalytique opérant dans un tube moléculaire hydrosoluble, à savoir un catalyseur au nickel mis au point par nos équipes en 2003); par ailleurs, ce projet prend en compte la nécessité de remplacer, à moyen terme, des catalyseurs industriels existants, fonctionnant dans des solvants halogénés, par des systèmes plus efficaces et environementalement plus propres. Ce projet est interdisciplinaire et transfrontalier. Les chercheurs impliqués dans ce projet auront à intervenir dans trois équipes dont les expertises sont complémentaires, la première consacrant l'essentiel de ses activités à la synthèse moléculaire (UMR 7513, ULP Strasbourg, équipe de Dominique MATT), la seconde à la catalyse de polymérisation (UPR 22, Strasbourg, Institut Charles Sadron, équipe de Pierre LUTZ), et la troisième, allemande, étant spécialisée dans la séparation/caractérisation de polyoléfines (Dr Harald PASCH, université de Darmstadt). Ce projet s'inscrit dans une thématique plus générale initiée en 1992 par Dominique MATT, consacrée à la chimie des métallo-cavitands. L'octroi d'un financement par l'ANR renforcerait de manière décisive notre attractivité vis-à-vis des étudiants étrangers que nous souhaitons accueillir dans le cadre de nos implications internationales (notamment au sein du réseau containers moléculaires et du Laboratoire Européen associé Macromolécules en milieux divisés ) Méthodologies: réactions en autoclave, sous moyennes pressions; réactions en conditions supercritiques; synthèse organique et organométallique; analyses hplc, GC, SEC à haute température

The gas ethylene is one of the earliest characterised plant hormones. In particular the response of germinating seedlings towards ethylene, has facilitated the isolation and characterisation of many of its components using forward mutagenesis. Based on the identified mutants a detailed model of the ethylene response pathway in the model plant Arabidopsis thaliana has been built: Ethylene signal transduction begins with ethylene binding to and inactivating a family of ethylene receptors. In the absence of ethylene, these receptors activate CTR1, a mitogen activating protein kinase kinase kinase. After CTR1 inactivation, EIN2 promotes ethylene responses via the downstream transcription factor EIN3. EIN3 then activates primary targets of the ethylene response cascade. The transcription factor EIN3 has recently been shown by us and others to be regulated at the posttranslational level by the F-box proteins EBF1 and EBF2 and this regulation is of crucial importance for the vast majority of the great many developmental and growth responses to the hormone ethylene (Potuschak et al.,2003; Guo & Ecker; 2003; Gagne et al, 2004). F-box proteins are substrate binding components of ubiquitin ligating SCF complexes that target substrate proteins for proteasomal degradation (Lechner et al., 2006). In the absence of ethylene, EIN3 protein is constitutively degraded in an EBF1/2 dependent manner. However in the presence of ethylene, EIN3 is stabilised and accumulates. Likewise ebf1ebf2 mutants accumulate high levels of EIN3 protein already in the absence of ethylene and display a strong constitutive ethylene response phenotype. We previously showed that the accumulation of EIN3 positively regulates EBF1 and EBF2 mRNA levels, which presumably provides a feedback mechanism to limit the accumulation of EIN3. At the protein level ethylene dependent protein accumulation of EIN3 is completely abolished in ein2 mutant plants, reduced in ein5 and ein6 mutants, and increased in the constitutive ethylene response mutant ctr1 (Guo&Ecker, 2003). The reduced accumulation of EIN3 protein is in general matched with a reduced accumulation of EBF2 and , to a lesser extent, EBF1 transcripts in ein2, ein3 and ein6 plants whereas ctr1 plants have elevated EBF1/2 RNA levels (Potuschak et al., 2003). These sole exception to this pattern is the ein5 mutant in which reduced EIN3 accumulation is matched with moderately increased EBF1 and EBF2 levels. EIN5 was recently identified by us and others as being allelic to the cytoplasmic exoribonuclease XRN4 (Olmedo et al., 2006; Potuschak et al., 2006). While EBF1/2 mRNA levels are elevated in an ein5/xrn4 mutant background, it is unlikely that EBF1/2 mRNAs are themselves direct targets of XRN4: EBF1/2 mRNA levels remain short lived in ein5/xrn4 mutants; we and others were not able to show stabilisation of EBF1/2 mRNAs in xrn4 mutant plants (Potuschak et al., 2006, Souret et al., 2004). We therefore deem it more likely that XRN4 acts on an upstream transcriptional regulator of EBF1/2. Taken together the interdependence of EBF1/2 dependent turnover and EIN3 dependent transcription of EBF1/2 and the modulation of EBF1/2 mRNA levels by XRN4 indicates that transcriptional regulation of EBF1/2 appears to be an important and recurring theme in the regulation of EIN3 protein accumulation and in plant ethylene signalling indeed. We therefore will investigate how EBF1and 2 are transcriptionally regulated in greater detail. In particular we would like to know if EIN3 directly targets EBF1/2 promoters or if it acts through downstream components of the ethylene response cascade such as ERF1. Our interest in the transcriptional regulation of EBF1/2 has been further increased by several recent microarrray studies that show misexpression of either EBF1, EBF2 or both and in one case EIN3 itself in response to other hormones or in response to pathogens derived signals. It is widely known that different plant hormone signalling pathways int.

Metalloenzymes with transition metal-sulfide complexes located at their active sites play a key role in several metabolic pathways comprising carbon fixation processes as well as redox processes. Because of the simplicity of these metal-sulfide complexes and the diversity of their functions, their prebiotic origin was postulated and it has been envisaged that transition metal sulfides might have played a role as primitive catalysts in the first steps of chemical evolution. In this respect, hydrothermal vents might be considered as ideal sites where these first steps might have occurred. Indeed, the fluids which are emitted in the seawater at these sites contains various transition metal sulfides (e.g. Fe, Ni, Co sulfides) and gases (H2S, CO2, CO, H2, COS, notably) to which a role in prebiotic chemistry has been postulated. This is a very active field, at the moment, as shown by the recent publication of a series of important articles devoted, in this context, to the investigation of the potential of transition metal sulfide chemistry in prebiotic chemistry. Our project is devoted, to the investigation of a central question of prebiotic chemistry, which was underestimated so far, namely the origin of lipids. This is a key issue since compartimentalization is a perequisite for the emergence of cellular life. Therefore, a viable prebiotic pathway to their synthesis would fill an important gap in the first steps of chemical evolution. Indeed, amphiphilic molecules would enable the spontaneous formation of micelles/vesicles able to encapsulate organic molecules and to catalyze various reactions of prebiotic interest based on hydrophobic interactions. The main objective of our project is to evaluate the potential of the conditions prevailing in the vicinity of hydrothermal vents and of the catalysis by transition metal sulfides for the formation of high molecular weight functionalised lipids (ideally >C10), potential precursors of membrane constituents by means of laboratory simulation experiments. These experiments will involve the constituents of the fluids emitted in the seawater at hydrothermal vents such as H2S, various transition metal sulfides, as well as C1 carbon sources comprising CO2, CO and COS. This project is based on preliminary studies which have been performed very recently at the Laboratoire de Géochimie Bioorganique, and which led to the discovery of a geochemically plausible iterative pathway leading from CO2/CO and H2S to thiols, carboxylic acids, thioacids and thioesters (limited to C4 so far), under aqueous conditions and in the presence of iron and nickel sulfides as catalysts. Several approaches might be envisaged to favour the formation of functionalized amphiphilic lipids. These approaches, which of course must be geochemically relevant, will take into account the main factors influencing the yields of the successive elongation steps in the overall pathway studied so far. One might envisage, in a first stage, improving and optimizing the transition metal catalysts used. It is clear, in this respect, that the nature of the transition metal sulfides, their mineralogical phases as well as the specific surface available will influence their efficiency. This might be achieved, notably, by dispersing the transition metal sulfides on the surface of other minerals (such as clays for instance) and by extending the set of catalysts used limited, so far, to Fe and Ni sulfides to Co, Cu, Zn, Mn, Co, Pb sulfides, which also occur at the hydrothermal vents. In a second stage, we envisage to improve the various steps involved in the iterative chain elongation pathway by limiting the reactions leading to dead ends (like carboxylic acids) by various geochemically relevant approaches involving notably, the use of, polyphosphates as additional reagents. This would allow the carboxylic acids to be transformed into related thioacids/thioesters (via acylphosphates) able to enter again the chain elongation process. Experi...

To understand the progressive emergence of complex functions at the molecular level, it is essential to bridge the gap between global brain function and molecular neuroscience. Fortunately, the brain is modular: neuronal networks of the cerebral cortex are organized in local circuits or modules that serve different functions in specific brain regions, from the forebrain to the spinal cord. A given cortical area is composed of many functional modules that allow a parallel processing of incoming information. Ocular dominance columns in the visual cortex, glomeruli in the olfactory bulb and the barrel of the somato-sensoricortex are considered as paradigms of the modular organization of information processing in the brain. One major challenge of current neuroscience is to unravel the operational modes of these modules or ‘microcircuits’ . The cerebellum plays a major role in the control and learning of skilled movements. Recent evidence has demonstrated that the cerebellar cortex plays a role in the precise timing of individual components of the motor program and is involved in the synchronization of cerebello-thalamo-cortical oscillations observed during motor tasks. To understand, and ultimately manipulate, the integrative role of the cerebellum in the motor circuit its input/output transformation needs to be elucidated. Although the cellular organization of the cerebellar cortex looks homogeneous across lobules and folia, anatomical and molecular data have shown that the cerebellum is also organized in modules. Functional studies have demonstrated that task-related modules can be identified and selectively modified. The organization of the basic microcircuit of the cerebellar cortex is now well described; however rules governing how incoming information is channelled through the microcircuitry and how the specific processing of one given input is carried out by the microcircuit are still poorly understood. Furthermore, the functional connectivity within and across individual modules has not yet been characterized. The major goal of this project is to identify operational modes of the unitary functional module in the cerebellar cortex. We will study intrinsic synaptic connections within a given module, intermodular synaptic connections between neighboring modules and Purkinje cell output to deep cerebellar nuclei, the actual output stage of the cerebellum. Since this requires isolating both individual modules and its specific inputs, we will then combine two recent optical tools. (1) The use of transgenic mice in which modules can be identified by GFP expression. (2) An optical genetically-targeted stimulation technique that permits the selective activation of identified input pathways targeting specific modules of the cerebellar cortex and pathways projecting to the output stage of the cerebellum. We postulate that targeting and identifying individual cerebellar modules will clarify the fundamental rules determining functional synaptic organization of the cerebellar modular system.