Les microorganismes, comme un grand nombre de cellules d'eucaryotes supérieurs sont généralement dans un état non prolifératif, dans l'attente de signaux spécifiques pour entamer un cycle de division. Chez la levure Saccharomyces cerevisiae, ce sont les nutriments présents dans le milieu de culture qui conditionnent l'état de prolifération. Les transitions entre état prolifératif et état quiescent impliquent non seulement l'adaptation du métabolisme mais aussi le remodelage de nombreuses structures cellulaires et notamment celles composées de filaments d'actines (F-actine). Le but de notre projet est l'étude du remodelage du cytosquelette d'actine lors des transitions entre prolifération et quiescence chez S. cerevisiae. Nous avons étudié les structures contenant de la F-actine au cours du passage d'un état prolifératif à un état quiescent suite à l'épuisement des nutriments dans le milieu de croissance. Cette étude préliminaire montre que les structures contenant des filaments d'actine caractéristiques des cellules en croissance disparaissent au profit d'un nouveau type de structures, plus dense, dont la forme et le nombre sont variables selon les cellules et que nous avons appelées blobs . En phase stationnaire, la majorité des cellules quiescentes présentent un à deux gros blobs de F-actine. Notre projet s'articule autour de deux grands axes. Dans un premier temps, nous étudierons la formation, la dynamique, la composition et la fonction des blobs d'actine. Pour cela nous utiliserons des approches de vidéo microscopie en trois dimensions et des techniques d'ablation de fluorescence (FRAP et FLIP) couplées à des approches de biochimie des complexes protéiques. Dans un deuxième temps, nous mettrons en évidence et étudierons les signaux qui régulent le remodelage du cytosquelette d'actine au cours des transitions entre quiescence et prolifération. Nous avons déjà identifié un des signaux les plus en amont de cette cascade de signalisation : le glucose. Nous utiliserons les puissants outils génétiques disponibles chez la levure pour identifier les différents acteurs qui conditionnent la formation et le maintien des blobs d'actine. A terme, ce projet devrait fournir un cadre expérimental unique pour étudier la mise en place de la polarisation cellulaire chez S. cerevisiae.

L’objectif est de comprendre les processus de construction des connaissances, celles de professionnels de santé, et celles de malades et leur famille, autour du diabète de type 2 - et d’un facteur de risque, la surcharge pondérale - du surpoids à l’obésité -, dans différents contextes professionnels et familiaux, en milieu urbain, à Bamako (Mali).

The objective of this project is the realisation of a new generation of Terahertz (THz) waveguide and the fabrication of an elementary component, the resonator, in the prospect of improving the conception of more complex and integrated THz systems. THz refers to electromagnetic wave spectrum form 100 GHz to 10 THz lying between microwave and optical spectra. In this domain, research interest has been substantially increasing due to the wide prospects of applications in astrophysics, biology, medicine, communication and security fields. However, the expansion of the THz domain requires the extension of microwave and optical technologies to develop building block functions for more complex and integrated components working at THz frequencies. In particular, the lack of competitive THz waveguide is a strong limiting factor. In this context, the interest of this project is the conception of THz-fibres based on the Photonic Band-Gap (PBG) guidance mechanism. These guides are composed by an hollow core surrounded by a photonic crystal cladding. Since the core is filled with air, the material absorption issue is avoided. Moreover, even if the photonic crystal is made with absorbent materials, if the induced PBG effect is sufficiently strong, the resulting waveguide attenuation is several orders lower than the material attenuation. This phenomenon allows the use of materials that are too absorbent for wave guidance by total internal reflection mechanism. In a first time, we will use silica glass (that has an attenuation around 50 dB/m at 0.5 THz) to design and fabricate a prototype with an attenuation around or lower than 1 dB/m. The performances of the prototype will be analysed with the help of dedicated characterisation tools that will be set up. A time domain based bench will be used to characterised transmission properties of the fibre and to optimise its opto-geometrical parameters. Based on this study, further improvements might be investigated. In order to extend the transmission window of the fibre to higher THz frequencies, the insertion of metal inclusions in the photonic crystal will be studied. These inclusions might increase the PBG effect, and thus, compensate the dramatic increase of silica absorption at frequencies above 1 THz. Finally, the use of less rigid materials like polyethylene will open the possibility to fabricate flexible THz-fibre. In a second time, the fabricated THz-fibre will be used as a building block for the conception of advanced components. The transposition of elementary functions (filtering, routing, switching) from microwave or optical to THz domains will be studied. Moreover, the size of THz wavelength allows the use of fabrication processes issued from both domains. In this prospect, we will realise a resonator. The association of a resonator configuration from microwave studies with the Thz-fibre properties (low attenuation and strong field confinement in the core) may yield a significative increase of the Q factor. The realisation of this resonator would be a significant illustration of the rich potential of this project for the conception of more complex and integrated functions and it opens the door to the development of a new generation of components dedicated to THz frequencies.

The UREKAT proposal focuses on Foldamers and on the challenging issue in the field of connecting structure and function. By taking its original inspiration both from biological and artificial chemical systems, the project proposes to develop, evaluate and optimize synthetic helical molecules bearing intrinsic anion-binding and/or catalytic properties (evaluated in asymmetric reactions and Ring-Opening Polymerization (ROP)). The project will concentrate on enantiopure, aliphatic, helically folded urea-oligomers, a non-oligoamide class of foldamers whose structures have recently been characterized at atomic resolution (Fischer et al. Angew. Chem. Int. Ed. 2010). The motivation to set-up this project stems from (1) the importance of protein anion recognition processes in biology (anion channels / transporters, enzymatic reactions) and the role of H-bond mediated interactions in conferring selectivity, (2) the finding that approaches based on ureas and thioureas have become prevalent in the design of synthetic anion receptors and hydrogen-bonding organocatalysts, (3) the robustness of the intramolecular three-centred H-bonding scheme in oligoureas that stabilize the helical fold, and (4) the versatility of this class of foldamers which bear an isostructural relationship with helix forming gamma-peptides. Oligoureas have been shown to be very effective in terms of interaction with biomolecules and for possible biomedical applications. In particular, helices designed to mimic host-defense peptides disrupt bacterial cell membranes and display potent antimicrobial activities. In UREKAT, we propose to go beyond the current state of the art in the field of foldamer applications, by taking advantage of two unique features of the helical urea backbone, i.e. the presence of: (1) a preformed binding site consisting of two urea head groups presented in an intrinsically chiral environment at one end of the helix (2) a macrodipole moment along the helix axis with a positive pole close to the binding site which could contribute to cooperative ligand binding. Properties such as anion selectivity and affinity, ligand binding, catalytic efficiency will be modulated and tuned by variation in capping groups, nature of side chains, and helix length and by discrete substitution of thiourea for urea. Short-chain helices such as those delivered by the end of the project, suitable for binding anions and H-bond mediated catalysis may be seen as a first step towards the design of more complex folded architectures mimicking more closely the structure and function of proteins, and enzymes in particular. This fundamental research program will be performed at the Institut Européen de Chimie et Biologie (IECB) in Bordeaux (France) which offers a very suitable environment in terms of facilities and complementary scientific expertises for the applicant.