Thesis Title: Metabolic profiling of Drosophila melanogaster: a new insight into the central metabolic pathways

Drosophila melanogaster is one of the most popular model organisms. After the full genome successfully sequenced, 75% of known human disease genes were found to match in the genome of Drosophila. With an attempt to fulfill the knowledge on this model organism, many metabolomics studies have been established. Since metabolomics is the latest “omics” field concerned with the high throughput identification and quantification of the small molecule metabolites, the obtained data can be the good reflection of an organism’s phenotype or physiology under a certain condition. However, most of the current reports on the metabolome of Drosophila just performed at a limited developmental stage such as larvae or adult. Each study was also focused on different biological issues so that the target metabolic pathways were also not consistent among those researches. Hence, the objective of this study is to elucidate global changes in the central metabolic pathways in Drosophila by using a metabolomics approach.

In Chapter 1, general introductions regarding Drosophila melanogaster model and the potential of using metabolomics on Drosophila studies are presented. In chapter 2, non-targeted GC/MS-based and targeted LC/MS-based metabolic profiling methods were conducted to obtain the general view on the changes of central metabolic pathways throughout Drosophila lifecycle. The obtained data showed that each metabolite had a distinct expression pattern throughout development. Utilizing multivariate analyses, the metabolic pathways that strongly correlated with the development in each stage including embryo, larvae, pupae and adult flies were also elucidated. In chapter 3, the effects of temperature and origin on metabolic profiles were also examined. The results in this study supported the experimental design for further metabolomics studies, where the temperature and genetic background of transgenic strains might directly affect the experimental results. In chapter 4, these approaches were successfully applied to study the role of Drosophila histone methyltransferase G9a. At last, general conclusion and future perspective are elaborated.