Background

All living organisms have a metabolism - a set of countless chemical reactions (or metabolic processes) that allows them to survive. The small-molecule intermediates and products of an organism’s metabolism are known as the metabolites and subsequently all the metabolites found in a system are denoted, the metabolome. Current technologies allow us to take a snapshot of the 'metabolome', providing a sensitive indicator of what is going on inside the organism, including its health and nutritional status.

In our bodies, as in all multicellular organisms, the metabolomes of different tissues are likely to differ significantly, reflecting the different specialized jobs they perform. Studying the composition of tissues in humans is obviously hard to perform, however the tiny fruit fly Drosophila has proved itself to be an excellent ‘model’ for many human processes. Indeed, much of our understanding of how humans develop, or of how our body clocks work, is based on research first performed in Drosophila.

The primary aim of this project is to generate metabolomes for the major tissues of Drosophila and to place them online in the public domain. This dataset should prove invaluable for the rapidly growing population of scientists studying metabolism in Drosophila - for example to model the natural ageing process or obesity and diabetes. It is hoped that by providing modelling techniques and tools for the data will allow for a greater understanding of human biology. Additionally, 70% of human genetic diseases are mutations in metabolic enzymes. These mutations can either be directly harmful or damage organs, like the kidney, by uncontrolled accumulation of metabolites. Notably, 80% of human genes have a Drosophila homologue, making it possible to model many inborn errors of human metabolism in the fruit fly; assess the impact of these mutations by metabolomics approaches; and use the mutants in drug-screens to work towards alleviating these life-limiting conditions.

The benefits of this project are not likely to be specific to biomedicine: Over one million lives are still lost annually to insect-borne diseases such as malaria and dengue; and insects are also key vectors of animal disease, such as bluetongue virus. Drosophila, with its potent genetic tools, is an ideal model for such insect pests. Unravelling insect metabolism may help to clarify the mechanisms by which insects render insecticides harmless, and/or identify new targets for novel, greener, insecticides.

This three-year project is funded by the UK’s BBSRC.