From physics to metaphysics: philosophy and style in the critical writings of T. S. Eliot (1913-1935)

This thesis considers Eliot's critical writing from the late 1910s till the mid-1930s, in the light of his PhD thesis - Knowledge and Experience in the Philosophy of F. H. Bradley - and a range of unpublished material: T S. Eliot's Philosophical Essays and Notes (1913- 4) in the Hayward Bequest (King's College, Cambridge University); T. S. Eliot's Family Papers in the T. S. Eliot Collection at the Houghton Library (Harvard University); and items from the Harvard University Archives at the Pusey Library. 'Me thesis offers a comprehensive view of Eliot's critical development throughout this important period. It starts by considering The Sacred Wood's ambivalence towards the metaphysical philosophy of F. H. Bradley and Eliot's apparent adoption of a scientific method, under the influence of Bertrand Russell. It will be argued that Eliot uses rhetorical strategies which simultaneously subvert the method he is propounding, and which set the tone for an assessment of his criticism throughout the 1920s. His indecision, in this period, about the label 'Metaphysical' for some poets of the seventeenth century, reveals the persistence of the philosophical thought he apparently rejects in 1916, when he chooses not to pursue a career in philosophy in Harvard. This rhetorical tactic achieves its fulfilment in Dante (1929), where Eliot finds a model in the medieval allegorical method and 'philosophical' poetry. Allegory is also examined in connection with the evaluation of Eliot's critical writings themselves to determine, for instance, the figurative dimension of his early scientific vocabulary and uncover metaphysical residues he had explicitly disowned but would later embrace. Finally, it is suggested that, the hermeneutics of allegory are historical and it is used here to test the relationship between Eliot's early and later critical writings, that is the early physics and the later metaphysics.

Filling in gaps of Drosophila melanogaster urate degradation metabolic pathway using metabolomics approaches: towards the core metabolome of the fruit fly

The primary goal of systems biology is to integrate complex omics data, and data obtained from traditional experimental studies in order to provide a holistic understanding of organismal function. One way of achieving this aim is to generate genome-scale metabolic models (GEMs), which contain information on all metabolites, enzyme-coding genes, and biochemical reactions in a biological system. Drosophila melanogaster GEM has not been reconstructed to date. Constraint-free genome-wide metabolic model of the fruit fly has been reconstructed in our lab, identifying gaps, where no enzyme was identified and metabolites were either only produced or consume. The main focus of the work presented in this thesis was to develop a pipeline for efficient gap filling using metabolomics approaches combined with standard reverse genetics methods, using 5-hydroxyisourate hydrolase (5-HIUH) as an example. 5-HIUH plays a role in urate degradation pathway. Inability to degrade urate can lead to inborn errors of metabolism (IEMs) in humans, including hyperuricemia. Based on sequence analysis Drosophila CG30016 gene was hypothesised to encode 5- HIUH. CG30016 knockout flies were examined to identify Malpighian tubules phenotype, and shortened lifespan might reflect kidney disorders in hyperuricemia in humans. Moreover, LC-MS analysis of mutant tubules revealed that CG30016 is involved in purine metabolism, and specifically urate degradation pathway. However, the exact role of the gene has not been identified, and the complete method for gap filling has not been developed. Nevertheless, thanks to the work presented here, we are a step closer towards the development of a gap-filling pipeline in Drosophila melanogaster GEM. Importantly, the areas that require further optimisation were identified and are the focus of future research. Moreover, LC-MS analysis confirmed that tubules rather than the whole fly were more suitable for metabolomics analysis of purine metabolism. Previously, Dow/Davies lab has generated the most complete tissue-specific transcriptomic atlas for Drosophila – FlyAtlas.org, which provides data on gene expression across multiple tissues of adult fly and larva. FlyAtlas revealed that transcripts of many genes are enriched in specific Drosophila tissues, and that it is possible to deduce the functions of individual tissues within the fly. Based on FlyAtlas data, it has become clear that the fly (like other metazoan species) must be considered as a set of tissues, each 2 with its own distinct transcriptional and functional profile. Moreover, it revealed that for about 30% of the genome, reverse genetic methods (i.e. mutation in an unknown gene followed by observation of phenotype) are only useful if specific tissues are investigated. Based on the FlyAtlas findings, we aimed to build a primary tissue-specific metabolome of the fruit fly, in order to establish whether different Drosophila tissues have different metabolomes and if they correspond to tissue-specific transcriptome of the fruit fly (FlyAtlas.org). Different fly tissues have been dissected and their metabolome elucidated using LC-MS. The results confirmed that tissue metabolomes differ significantly from each other and from the whole fly, and that some of these differences can be correlated to the tissue function. The results illustrate the need to study individual tissues as well as the whole organism. It is clear that some metabolites that play an important role in a given tissue might not be detected in the whole fly sample because their abundance is much lower in comparison to other metabolites present in all tissues, which prevent the detection of the tissue-specific compound.