Our research group at UGSF has shown that, in the unicellular green alga Ostreococcus tauri, the division of the unique starch granule coincides with that of the unique plastid. We have postulated that this coordination was required to ensure the presence of priming molecules for starch synthesis and preserve the continuity of starch metabolism. The preexistence of such starch-like primers seemed mandatory in O. tauri because it was impossible to completely remove starch of this organism even after the cells were left for several days in the darkness. Although the situation is different in higher plants (because of the apparent absence of control of starch grains distribution in the daughter structures after plastid division), the question of the control of starch initiation during plastid division remains unsolved. The presence of dense, water-insoluble semi-crystalline starch granules might create an overwhelming problem during the plastid splitting by the constriction ring. Moreover, at UGSF we have also demonstrated the primary function of the SS4 protein in the initiation of starch synthesis in Arabidopsis thaliana. In addition, an EzrA-like coiled-coil motif was evidenced in the N-terminal region of SS4. EzrA is a bacterial regulator that controls the localization of the division ring formed, amongst others, by the FtsZ protein. This suggests that SS4 could be involved in the process that synchronizes plastid division and the seeding of the starch granules in higher plants. The existence of such a relationship is reinforced by our own observations showing that KO mutants or over-expressing lines of the plant FtsZ1 have only one plastid per cell containing starch granules of altered size and shape. Several publications describe that the alteration of plastid division modifies the size and shape of the starch grain in potato and rice. These results suggest that a coregulation exists between starch metabolism and specific factors of plastid division. However, the rationale and the precise underlying molecular mechanism of such cross-talk are still unknown. In this project, we first propose to analyze starch accumulation, structure, size and granule number per plastid in mutants impaired in plastid division. The link between plastid division and starch initiation will be evidenced by genetics approaches based on the combination of mutations (between ss4- or ss3- and ftsZX or arc6- mutants) and by searching for SS4 interacting partners. The identification of SS4 partners is ongoing by a wide untargeted Y2H approach (ULTimate Y2H yeast two-hybrid technology developed by Hybrigenics) using SS4 as bait. We will confirm the interactions by a classical 1-by-1 Y2H approach and other techniques such as coimmunoprecipitation. Protein complexes will be localized in leaves or roots by BiFC. The dynamics of FtsZ, ARC and SS4 protein localization will be investigated in both leaves and roots. Finally we will elucidate the function of SS4 in the priming process of starch synthesis by (i) the determination of the kinetic parameters of SS4 and the structural characterization of its products and (ii) the expression, in the ss4- null mutant, of different recombinant forms of SS4 deleted for the coiled-coil domain or specifically altered at the two highly conserved catalytic sites of the enzyme.

In recent years, tremendous efforts have been focused on the design of novel ways to target drugs to specific cells or organs. One highly promising strategy is the design of efficient delivery systems for which the drug release can be triggered by a photochemical event. The drug can be linked covalently to a carrier, or encapsulated within a porous nano-delivery system. Irradiation of the prodrug system within the organ to treat must lead to the rapid cleavage of the bond between the drug and the carrier, for carrier-based prodrugs, or to the “opening” of nano-delivery systems. The chemical bonds involved in the assembly of the delivery systems determine the complexity of the synthetic work and the fragmentation properties upon irradiation. To date, different linkers have been designed for this purpose. Usually, they require complex protection schemes for the assembly or lead to suboptimal fragmentation rates. Recently, the IBL team has designed a novel strategy named click-unclick (CC) allowing both the site-specific assembly of prodrugs and the subsequent rapid release of the active substance at the delivery site. The CC strategy involves first a novel click-type reaction which leads to the chemoselective assembly of the prodrug. Because the bond is formed chemoselectively, the assembly of the prodrug is considerably simplified compared to known strategies. Importantly, the bond formed in this process for assembling the constituents of the prodrug is used in the second step to unclick the drug at the site of delivery. For the moment, the unclick process was triggered by a biochemical (proteolytic enzyme) or a chemical (pH change). The aim of this project is to trigger the unclick process using a photochemical event, and to use the CC strategy for assembling novel peptide-based prodrugs and nano-delivery systems. The nano-delivery systems will be assembled by closing the pores of porous nanoparticles with dendrimers. Here, the CC strategy is used for closing/opening the nanoparticles filled with model anticancer drugs. The project includes also novel synthetic developments to facilitate the introduction of key functional groups for the click-unclick strategy.

“The notion of condition in Law takes place in different settings, in different times. The particularities of each one of these conditions involve different consequences. These consequences have rather real influences, even if the conditions can be fictive themselves. While conditions constitute a central theme for jurisprudence, the multiplicity of the notion of condition represents also a central theme for the History of Logic. Nevertheless, it is well known that the jurisprudential perspective and the philosophical perspective do not blend naturally, without any problem. It is due to this fact that the present project takes as a mission the study of the tensions in the relations between Law and Logic, and this study will be accomplished according to three particularly significant contexts: the ancient Roman period, G. W. Leibniz, and the contemporary Law. The main objective of the project is the coordination of the juridical and logical aspects of the notion of condition, in order to promote in a decisive manner the constitution of a universal juridical logic. The three periods already mentionned are historically relevant, each one for their own reasons, and they will represent our three main research points. They constitute a connection between logical and juridical approach of the notion of condition, and they manifest through the History the conscience of a special problematic, which raises many discussions in the contemporary research. It is evident by the description that we have rendered that the problematic of our project concerns the writings of Leibniz and, according to our approach, we also suggest that the framework of the dialogical logic, which nowadays reaches significant improvements, represents a promising background for the philosophical interpretation of it. Thus, we expect to open new perspectives in the study of the challenge of the interface between juridical representation and logical modeling in each one of the three researching points mentioned above, but also in a transversal manner across them.”