Saccharomyces Cerevisiae as a biotechnological tool for ageing research:studies on translation and metabolism

The yeast Saccharomyces cerevisiae is an important model organism for the study of cell biology. The similarity between yeast and human genes and the conservation of fundamental pathways means it can be used to investigate characteristics of healthy and diseased cells throughout the lifespan. Yeast is an equally important biotechnological tool that has long been the organism of choice for the production of alcoholic beverages, bread and a large variety of industrial products. For example, yeast is used to manufacture biofuels, lubricants, detergents, industrial enzymes, food additives and pharmaceuticals such as anti-parasitics, anti-cancer compounds, hormones (including insulin), vaccines and nutraceuticals. Its function as a cell factory is possible because of the speed with which it can be grown to high cell yields, the knowledge that it is generally recognized as safe (GRAS) and the ease with which metabolism and cellular pathways, such as translation can be manipulated. In this thesis, these two pathways are explored in the context of their biotechnological application to ageing research: (i) understanding translational processes during the high-yielding production of membrane protein drug targets and (ii) the manipulation of yeast metabolism to study the molecule, L-carnosine, which has been proposed to have anti-ageing properties. In the first of these themes, the yeast strains, spt3?, srb5?, gcn5? and yTHCBMS1, were examined since they have been previously demonstrated to dramatically increase the yields of a target membrane protein (the aquaporin, Fps1) compared to wild-type cells. The mechanisms underlying this discovery were therefore investigated. All high yielding strains were shown to have an altered translational state (mostly characterised by an initiation block) and constitutive phosphorylation of the translational initiation factor, eIF2a. The relevance of the initiation block was further supported by the finding that other strains, with known initiation blocks, are also high yielding for Fps1. A correlation in all strains between increased Fps1 yields and increased production of the transcriptional activator protein, Gcn4, suggested that yields are subject to translational control. Analysis of the 5´ untranslated region (UTR) of FPS1 revealed two upstream open reading frames (uORFs). Mutagenesis data suggest that high yielding strains may circumvent these control elements through either a leaky scanning or a re-initiation mechanism. In the second theme, the dipeptide L-carnosine (ß-alanyl-L-histidine) was investigated: it has previously been shown to inhibit the growth of cancer cells but delay senescence in cultured human fibroblasts and extend the lifespan of male fruit flies. To understand these apparently contradictory properties, the effects of L-carnosine on yeast were studied. S. cerevisiae can respire aerobically when grown on a non-fermentable carbon source as a substrate but has a respiro-fermentative metabolism when grown on a fermentable carbon source; these metabolisms mimic normal cell and cancerous cell metabolisms, respectively. When yeast were grown on fermentable carbon sources, in the presence of L-carnosine, a reduction in cell growth and viability was observed, which was not apparent for cells grown on a non-fermentable carbon source. The metabolism-dependent mechanism was confirmed in the respiratory yeast species Pichia pastoris. Further analysis of S. cerevisiae yeast strains with deletions in their nutrient-sensing pathway, which result in an increase in respiratory metabolism, confirmed the metabolism-dependent effects of L-carnosine.

Translation as an ideological interface : English translations of Hitler's Mein Kampf

The present thesis is located within the framework of descriptive translation studies and critical discourse analysis. Modern translation studies have increasingly taken into account the complexities of power relations and ideological management involved in the production of translations. Paradoxically, persuasive political discourse has not been much touched upon, except for studies following functional (e.g. Schäffner 2002) or systemic-linguistic approaches (e.g. Calzada Pérez 2001). By taking 11 English translations of Hitler’s Mein Kampf as prime examples, the thesis aims to contribute to a better understanding of the translation of politically sensitive texts. Actors involved in political discourse are usually more concerned with the emotional appeal of their message than they are with its factual content. When such political discourse becomes the locus of translation, it may equally be crafted rhetorically, being used as a tool to persuade. It is thus the purpose of the thesis to describe subtle ‘persuasion strategies’ in institutionally translated political discourse. The subject of the analysis is an illustrative corpus of four full-text translations, two abridgements, and five extract translations of Mein Kampf. Methodologically, the thesis pursues a top-down approach. It begins by delineating sociocultural and situative-agentive conditions as causal factors impinging on the individual translations. Such interactive and interpersonal factors determined textual choices. The overall textual analysis consists of an interrelated corpus-driven and corpus-based approach. It demonstrates how corpus software can be fruitfully harnessed to discern ‘ideological significations’ in the translated texts. Altogether, the thesis investigates how translational decision-makers attempted to position the source text author and his narrative in line with overall rhetorical purposes.

Evaluating choices:the role of corpora in translation choices and target text assessment

Translation training in the university context needs to train students in the processes, in order to enhance and optimise the product as outcome of these processes. Evaluation of a target text as product has often been accused of being a subjective process, which does not easily lend itself to the type of feedback that could enable students to apply criteria more widely. For students, it often seems as though they make different inappropriate or incorrect choices every time they translate a new text, and the learning process appears unpredictable and haphazard. Within functionalist approaches to translation, with their focus on the target text in terms of functional adequacy to the intended purpose, as stipulated in the translation brief, there are guidelines for text production that can help to develop a more systematic approach not only to text production, but also to translation evaluation. In the context of a focus on user knowledge needs, target language conventions and acceptability, the use of corpora is an indispensable tool for the trainee translator. Evaluation can take place against the student's own reasoned selection process, based on hard evidence, against criteria which currently obtain in the TL and the TL culture. When trainee and evaluator work within the same guidelines, there is more scope for constructive learning and feedback.