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International audience; Down syndrome is a genetic disorder caused by the presence of a third copy of chromosome 21, associated with intellectual disabilities. Down syndrome is associated with anomalies of both the nervous and endocrine systems. Over the past decades, dramatic advances in Down syndrome research and treatment have helped to extend the life expectancy of these patients. Improved life expectancy is obviously a positive outcome, but it is accompanied with the need to address previously overlooked complications and comorbidities of Down syndrome, including obesity and diabetes, in order to improve the quality of life of Down syndrome patients. In this focused review, we describe the associations between Down syndrome and comorbidities, obesity and diabetes, and we discuss the understanding of proposed mechanisms for the association of Down syndrome with metabolic disorders. Drawing molecular mechanisms through which Type 1 diabetes and Type 2 diabetes could be linked to Down syndrome could allow identification of novel drug targets and provide therapeutic solutions to limit the development of metabolic and cognitive disorders.

The type III effector DspA/E is an essential pathogenicity factor of the phytopathogenic bacterium Erwinia amylovora. We showed that DspA/E was required for transient bacterial growth in nonhost Arabidopsis thaliana leaves, as an E. amylovora dspA/E mutant was unable to grow. We expressed DspA/E in A. thaliana transgenic plants under the control of an oestradiol-inducible promoter, and found that DspA/E expressed in planta restored the growth of a dspA/E mutant. DspA/E expression in these transgenic plants led to the modulation by at least two-fold of the expression of 384 genes, mostly induced (324 genes). Both induced and repressed genes contained high proportions of defence genes. DspA/E expression ultimately resulted in plant cell death without requiring a functional salicylic acid signalling pathway. Analysis of A. thaliana transgenic seedlings expressing a green fluorescent protein (GFP):DspA/E fusion indicated that the fusion protein could only be detected in a few cells per seedling, suggesting the degradation or absence of accumulation of DspA/E in plant cells. Consistently, we found that DspA/E repressed plant protein synthesis when injected by E. amylovora or when expressed in transgenic plants. Thus, we conclude that DspA/E is toxic to A. thaliana: it promotes modifications, among which the repression of protein synthesis could be determinant in the facilitation of necrosis and bacterial growth.

TOR (Target Of Rapamycin) est une protéine kinase de la famille des PIKK (PhosphatidylInositol Kinase-related Kinases), essentielle à la survie, et très conservée entre les organismes eucaryotes. TOR fonctionne sous forme de deux complexes multiprotéiques, TORC1 et TORC2, intégrant des signaux environnementaux (les facteurs de croissance, l’état énergétique, les stress, la disponibilité en nutriments) et régulant la croissance via le contrôle de différentes fonctions cellulaires (la traduction, la biogenèse des ribosomes, la transcription, l’autophagie, le cycle cellulaire, le métabolisme, l’organisation du cytosquelette d’actine). TORC1 et TORC2 sont composés de protéines partenaires différentes et ont des rôles distincts au sein de la cellule. TORC1 comprend principalement les protéines TOR, RAPTOR et LST8, et TORC2 est composé de TOR, LST8 et RICTOR. Le génome d’Arabidopsis contient un gène Tor, deux gènes Lst8 et deux gènes Raptor mais pas d’orthologue du gène Rictor, ce qui remet en cause l’existence d’un complexe TORC2 chez les plantes. L’objectif de ma thèse est d’étudier les éléments en amont et en aval de la voie de signalisation TOR, et l’organisation du complexe TOR chez Arabidopsis. L’étude de la protéine LST8 a révélé un rôle très important de cette protéine dans la croissance, le développement, l’induction de la floraison, le métabolisme azoté et l’adaptation à des conditions de jour long. En parallèle, l’étude, via différentes approches, de lignées d’Arabidopsis permettant une inactivation inductible par l’éthanol de l’expression du gène Tor a permis de mettre en évidence des cibles et des fonctions cellulaires potentielles du complexe TOR chez Arabidopsis.

National audience; Drought is certainly one of the main abiotic stresses that our forests will have to face to in the near future, especially in the Mediterranean basin where climatic change forecasts predict a 1.5 to 4°C increase in temperatures. Compared to what is known in annuals, relatively few are known regarding the molecular responses of perennials to water deficit. Natural populations of Maritime pine, with ecotypes ranging from very dry to wet areas, constitute an excellent system to study forest tree adaptation to drought. Exploring the molecular plasticity of two ecotypes contrasting in their edapho-climatic regimes should highlight molecular mechanisms that have been shape by natural selection to provide them the highest fitness. In this study, we used a factorial design crossing two contrasted ecotypes by different watering conditions (control, 6h, 48h, 3 weeks of stress). Water deficit was applied using PEG as osmoticum in hydroponics on 8 weeks old seedlings. Physiological and metabolic characterizations of the plants (roots and leaves) were first carried out to evaluate the intensity of the imposed stress. Then, expression profiles in roots were obtained using a 7.2K maritime pine cDNA micro-array. Our primary interest was for gene showing contrasted reaction norms between the two ecotypes, among which we found genes involved in cell wall composition, osmoregulation, terpene biosynthesis, general stress response and regulation of transcription. Whether these genes really matter is validated by population geneticists who describe their landscape of nucleotide diversity and in particular molecular signatures of natural selection.

Diplôme : DES

It is predicted that Global Warming will greatly affect the development of forest tree species on a timescale of a single tree generation (from decades to centuries). Indeed, growth and wood quality strongly depend on water availability. Genetic ressources that are adapted to water deficit is a prerequisite to guarantee the sustainibility of forest ecosystems. In this context, a research program on maritime pine was launched with the main objective to understand genetic, physiological and molecular adaptation mechanisms for this species. Two-dimensional gel electrophoresis patterns of root proteins for 2 ecotypes (landes and moroccan) submitted or not submitted to drought stress were compared. This allowed to identify 696 proteins varying according to ecotype, stress, or interaction between these two factors. In order to characterize the specific strategies of each ecotype, we mainly focused on proteins showing (ecotype x treatment) interaction effect, i.e. presenting contrasting expression profiles. A total of 96 proteins were sequenced by tandem-mass spectrometry and 66 of them were unambiguously annotated based on sequence query in the SWISSPROT and TIGR database. Finally, these data made it possible to identify trends in protein expression patterns for each ecotype and propose hypothesis on specific response-strategies. Soon, the analysis of an additionnal set of 96 proteins could enable us to precise our conclusions and connect the different molecular elements and mechanisms identified in this study, Le réchauffement climatique prévu dans les années à venir va affecter le bon développement des arbres sur une échelle de temps correspondant à une seule génération (dizaines à des centaines d’années). En effet, la croissance et la qualité du bois en particulier dépendent étroitement des réserves d’eau. La disponibilité de ressources génétiques adaptées à ces nouvelles contraintes hydriques devrait permettre de garantir la pérennité des écosystèmes forestiers. Dans ce cadre, les recherches en cours sur le pin maritime visent à comprendre les mécanismes génétiques, physiologiques et moléculaire de l’adaptation de cette espèce. La comparaison des profils d’électrophorèse bidimensionnelle des protéines de racine des deux écotypes (landais et marocain) soumis ou non à un stress hydrique a permis d’identifier 696 protéines dont l’accumulation variait en fonction de l’écotype, du stress ou de l’interaction de ces deux facteurs. Afin de caractériser les stratégies spécifiques aux deux écotypes, nous nous sommes principalement focalisés sur des protéines montrant un effet d’interaction (écotype x traitement), c’est-à-dire traduisant le plus souvent des profils d’expression opposés entre les 2 écotypes. 96 protéines ont été séquencées par spectrométrie de masse et 66 d’entre elles ont pu être annotées sans ambiguïté grâce à l’interrogation des banques de données SWISSPROT et TIGR. Ces données nous ont conduits à dégager des tendances comportementales propres à chaque écotype et d’émettre des hypothèses quant à leur stratégie de réponse au stress. Bientôt, l’analyse de 96 protéines supplémentaires devrait nous permettre de préciser nos conclusions et de relier les différentes composantes moléculaires identifiées