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This thesis will examine the velocity structure of Austfonna, a large ice cap in the Svalbard archipelago. The remoteness of its location had previously hindered detailed observation by traditional methods, but indirect evidence suggested that it had the potential to be dynamically interesting. A recently developed remote sensing technique, SAR interferometry (inSAR), has allowed us to obtain the most detailed map of Austfonna's topography to date, plus unprecedented synoptic measurements of its velocity field. A four year time series of data acquired by the European Remote Sensing satellites ERS-1 and ERS-2 has been used to delineate active and inactive areas of the ice cap, which suggest that past ideas about Austfonna's thermal structure may need to be re-examined. It has also revealed large temporal velocity variations in one of its major drainage basins. These are difficult to classify because intermittent sampling has prevented us from determining their temporal wavelength, and also because globally the database of observed glacier velocity variations is so sparse that the range of possible variable flow scenarios is unknown. The work here demonstrates the huge potential for inSAR in helping to resolve such issues, and in providing an invaluable resource for scientists monitoring the stability of the world's ice fields.

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Contrasting physiological requirements for T. brucei survival between procyclic (vector) and bloodstream (mammal) forms necessitate different molecular processes and therefore changes in protein expression. Transcriptional regulation is unusual in T. brucei because the arrangement of genes is polycistronic; however, genes which are transcribed together are subsequently cleaved into separate mRNAs by trans-splicing and are individually regulated. During the process of trans-splicing, a 39-nucleotide splice-leader RNA is added to the 5´ end of mRNA. In this study, gene regulation in trypanosomes will be examined in the context of the 7-methylguanosine cap attached to the 5´ end of the splice-leader. Interestingly, in addition to the capping enzymes identified in other eukaryotes, trypanosomatids have an additional guanylyltransferase and methyltransferase in the form of a bifunctional enzyme (TbCGM1). TbCGM1 was found to be essential in bloodstream form T. brucei, although the purpose of this bifunctional capping enzyme remains unclear. Null mutants of a related enzyme, monomeric methyltransferase TbCMT1, did not show an effect on cell viability in culture, however, the enzyme proved to be important for virulence in vivo. Complementary to the study of T. brucei capping enzymes, we worked to develop a method to allow structural analysis of the 5´mRNA cap by mass spectrometry. Following pre-mRNA processing, regulation of the mature mRNAs is a tightly controlled cellular process. While multiple stage-specific transcripts have been identified, previous studies using RNA-seq found that the changes in overall transcript level do not necessarily reflect the abundance of the corresponding proteins. We hypothesized that in addition to mRNA stability, mRNA recruitment to ribosomes may play a significant role in the regulation of gene expression in T. brucei. To approach this question, we performed RNA-seq of total, subpolysomal, and polysomal mRNA. This transcriptomic data was then correlated with published proteomic studies to obtain a global picture of the relative translation efficiencies and their relationship to steady-state protein levels between bloodstream and procyclic form T. brucei.

Gene expression in eukaryotes is dependent on the N-7 methylguanosine cap, located at the 5’ end of RNA pol II transcripts, which marks pre-mRNA for processing, stabilisation and translation initiation. The enzymes that catalyse the formation of the N-7 methylguanosine cap are recruited to RNA pol II at the initial stages of transcription. The final step in this process, N-7 methylation of the guanosine cap, is catalysed by the RNA guanine-7 methyltransferase, RNMT. RNA guanine-7 methylation is an essential process for cell viability and its up-regulation has been associated with cell transformation. However, the mechanistic details of RNMT function in mammalian cells remain elusive. In order to gain better understanding of the molecular mechanisms associated with RNA guanine-7 methylation, cellular RNMT complexes were purified from human cells and constituent proteins were identified using mass spectrometry. A novel component of the RNA guanine-7 methyltransferase complex was identified and designated as RAM (RNMT activating mini-protein). The vast majority of RNMT is found in a complex with RAM and vice versa.RAM is an RNA-binding protein, promoting recruitment of RNA to RNMT. RAM increases recombinant and cellular RNMT cap methyltransferase activity and is required for cap methylation in vivo. We therefore, describe RAM as an “obligate activator” of the human cap methyltransferase. As expected of a protein essential for cap methylation, RAM is required for gene expression, and RAM depletion results in loss of cell viability. Current studies are being focused on determining RAM/RNMT crystal structure as well as determining how the RNA guanine-7 methyltransferase complex is regulated within cells.

La présente recherche tente d’identifier et de décrire les conditions d’implantation qui ont été mises en place dans deux écoles élémentaires francophones de l’Ontario pour atteindre un stade de fonctionnement avancé, soit l’intégration (Leclerc, Moreau et Lépine, 2009a) des communautés d’apprentissage professionnelles (CAP). En utilisant un échantillon de directions d’école et d’enseignants qui travaillent à l’intérieur d’écoles où les CAP sont à un tel stade de fonctionnement, notre recherche a permis de relever quelles conditions ont été mises en place pour atteindre un fonctionnement avancé des CAP. Des entrevues semi-dirigées ont été menées auprès de deux directrices et de quatre enseignantes d’écoles élémentaires franco-ontariennes. Ces entrevues abordaient de grands thèmes tels que la structure des CAP, la culture de collaboration et les processus employés en CAP dans le contexte de l’école. Un questionnaire sur le sentiment d’efficacité personnelle fut aussi rempli par les directrices d’école. Les résultats mettent en évidence le rôle complexe de la direction d’école dans la mise en œuvre des CAP tout en précisant les conditions d’implantation des CAP mises de l’avant par deux directrices d’école. En fait, nous relevons l’importance de recevoir des appuis humains et financiers et un soutien par la recherche; d’instaurer des exigences organisationnelles « préparatoires »; de respecter des exigences organisationnelles de mise en place des CAP; d’assurer que la direction et les membres du conseil scolaire aient confiance et soient compétents; d’instaurer un leadership partagé entre la direction, le conseil scolaire et les enseignants du comité d’amélioration du rendement des élèves (CARE); de rédiger des objectifs SMART à partir de ressources particulières et aménager un parcours de fonctionnement; d’établir des structures physiques et d’encourager une culture de collaboration entre les enseignants. Les résultats de notre étude rejoignent ce qu’avancent les recherches au sujet de l’implantation de la structure organisationnelle – CAP – dans une école. Or, notre recherche sur le terrain permet d’apporter des précisions quant à ces conditions d’implantation. D’ailleurs, nous avons recensé certaines sous-catégories thématiques qui ne sont pas reflétées explicitement dans la littérature.