Supporting healthy ageing through the microbiota: A Drosophila model

Changes in the intestinal microbiota (dysbiosis) have been implicated in age-related decline, being correlated with measures of frailty in the elderly. However, the accessibility of this microbial population to simple interventions, such as diet or probiotics, has also highlighted its potential as a partner in the maintenance of life-long health. The rational design of interventions targeting the microbiota will require a greater understanding of the mechanistic basis of microbial influence on host health throughout the life course.
The fruit fly, Drosophila melanogaster, is one of the premier model organisms for ageing research and carries a simple intestinal microbiota containing a number of taxa found in the human intestine. We have shown that shifts in the aging Drosophila microbiota broadly echo those seen in ageing people, and are also strongly implicated in age-related decline (Clark et al 2015). This project will capitalize on these similarities, and the strengths of the Drosophila model, in order to characterise the molecular mechanisms that drive the impact of dysbiosis on host health
The first stage of this project will utilise detailed time-course studies of multiple markers of age-related decline. Our focus will be the characterisation of microbial influence on decline and will encompass the intestine and multiple distal tissues. In addition to the assays of age-related decline that we use in the Clark lab, the student will take a rotation in the Sanz lab (Newcastle) in order to measure the impact of microbial exposure and ageing on mitochondrial function in a number of tissues.
Following this, we will use metabolomic and transcriptomic approaches to measure change in metabolism and gene expression of the intestinal microbiota during host aging. These data will provide us with a number of candidate metabolic pathways or single genes that are modified with age and may drive the influence of the microbiota on host health. These data will therefore form the basis of the final stage of this project in which we will use the powerful genetic tools available in Drosophila in combination with bacterial genetics to test the impact of our candidates on age-related decline in the host. The techniques and tools used will be determined by the nature of the gene/pathway of interest, but will focus on identifying potential targets for interventions to prevent or delay decline across multiple tissues.