No description available.

No description available.

No description available.

No description available.

No description available.

This work examines the suitability of two different ontology approaches for the annotation of Schizosaccharomyces pombe (fission yeast) phenotypes derived from a number of screens of two fission yeast strain libraries- a temperature-sensitive library and an insertional library.

The Saccharomyces yeast are group of closely related species that can form viable but sexually sterile Fl hybrids. The hybrid sterility is thought to be due to sequence divergence that renders them genetically incompatible. Saccharomyces yeast hybrids contain two set of homologous genomic information from both parents that can be translated into biologically functional proteins. A large proportion of proteins would form complexes to carry out specific biological function.

No description available.

This research develops a detailed mathematical model of the fission yeast Schizosaccharomyces pombe. The objectives were to produce a mathematical model of a periodically fed system and to fit this model to experimental data, in order to investigate the cells' response to different periodic feeding strategies. Models that can accurately reproduce the dynamics of cell populations are potentially important in the design and control of bioreactors and can possibly be used to identify the dynamics of cell cycle checkpoints. A simple mathematical model based on Monod kinetics was found to be inadequate for this research as it was unable to replicate the results seen experimentally in periodically fed cultures. Hence a detailed mathematical model is required in order to consider the behaviour of the individual cells as a part of the overall population. CelCyMUS is a structured, segregated model based on the cell cycle that has been developed in previous research, and used as a basis for this study. In this work, the original CelCyMUS framework has been modified to include periodic feeding and the specific cell line used in this research. Three different versions of CelCyMUS have been investigated in order to determine which provides the closest match to the experimental data available. Modifications made to the model include an alternative glucose uptake rate expression and alternative transition rules for cells at the M/Gla phase boundary and within the G1b phase of the cell cycle. The modifications also remove any discontinuities from the mathematical models of the cell cycle. The key conclusions that can be drawn from this research are: The new model provides a much closer fit to the experimental data than all previous models. The new model is capable of producing chaotic behaviour. Simple mathematical models, including Monod, are not able to generate a chaotic response. The chaotic behaviour shown by the new version of CelCyMUS is not solely due to discontinuities that were present within the model. When CelCyMUS produces periodic behaviour under periodic feeding conditions, it can be seen that the cell population is highly synchronised. When a chaotic response is produced, the cell population shows partial or no synchronisation. It is suggested that the failure of the cell population to synchronise is the cause of the chaotic behaviour. When attempting to fit the model to experimental data, there is no single set of parameter values that will fit the model to the experimental data over the range of feed periods investigated. This suggests that the system dynamics are changing as the feed period is changed. Two major areas for further research work have been identified. The first is to modify CelCyMUS further to account for the changing behaviour of the cells at longer feed periods, possibly by introducing a quiescent phase that runs in parallel with the cell cycle. The second is to obtain more experimental data for both cells and glucose across a range of feed periods. This will give a better understanding of the cell dynamics within the system and allow further development of the mathematical model.

Candida albicans est une levure de la flore digestive humaine, pouvant dans certaines conditions s’avérer être un pathogène opportuniste. Différents glycoconjugués de la paroi de la levure, en particulier le phosphopeptidomannane (PPM), sont impliqués dans l’interaction hôte-pathogène notamment via des beta-1,2 oligomannosides (β-Mans) terminaux intervenant dans les mécanismes de virulence de la levure. Les travaux de thèse visent à mieux comprendre les voies de biosynthèse des β-Mans par l’étude des enzymes impliquées (CaBmts). Dans ce contexte, la première enzyme étudiée a été CaBmt1, impliquée dans l’initiation de la β-mannosylation du PPM. La stratégie d’étude a consisté d’une part en la préparation d’un panel important de substrats accepteurs potentiels et leur caractérisation structurale par spectrométrie de masse et RMN, et d’autre part à l’étude de l’activité enzymatique de Bmt1p, enzyme recombinante produite chez Pichia pastoris, en présence des substrats naturels et de substrats de synthèse. Nous avons démontré que Bmt1p était capable in vitro de transférer successivement deux résidus de mannose en β-1,2 sur un tri-ou tétramannoside lié en α-1,2. Dans la seconde partie, nous nous sommes intéressés à la caractérisation de l’activité de CaBmt3, enzyme impliquée dans l’élongation des β-Mans du PPM ; la même démarche a été retenue pour l’étude. Les résultats obtenus montrent que Bmt3p transfère in vitro un seul résidu mannose en β-1,2 sur un tétramannoside constitué d’une chaine en α-1,2 avec un mannose terminal lié en β-1,2. L’ensemble de ces travaux sont un préalable à l’élaboration de nouvelles drogues anti-fongiques ciblant la synthèse de la paroi. / Candida albicans is a commensal yeast present in human digestive flora; nevertheless, this opportunistic pathogen may cause severe infections. Several cell wall components including phosphopeptidomannan (PPM) are involved in C. albicans-host cells interaction especially by terminal beta-1,2 oligomannosides (β-Mans) known as implicated in the yeast virulence mechanisms. The aim of our work is to better understand biosynthetic pathways of β-Mans by the characterization of CaBmts individual activities. In this context, the first enzyme to be studied was CaBmt1, involved in the initiation of β-mannosylation of PPM. The strategy is based firstly on the preparation of a large panel of potential acceptor substrates and their structural characterization by mass spectrometry and NMR. On the other hand, the study of enzymatic activity of Bmt1p, a recombinant soluble form produced in Pichia pastoris, was performed in the presence of the natural substrates and synthetic substrates. We established that Bmt1p can sequentially transfer in vitro two -1,2-mannosyl units onto a α1-2 linked tri-or tetramannoside. The second part of this work focused on the characterization of the activity of CaBmt3, the enzyme involved in the elongation of the β-Mans chain on the PPM; the same approach was used for the study. Our results demonstrated that Bmt3p can catalyse the in vitro transfer of one -1,2-mannosyl unit onto a tetramannoside containing a terminal β-1,2-Man linked to a α(1-2)Man chain. These data are a prerequisite for the design of new potential antifungal drugs that target the biosynthesis of cell wall.