FULLY FUNDED PhD - Identifying Critical Periods for Mitochondrial Function in Drosophila Development and Lifespan
Project Overview
Why do some organisms age more gracefully than others? Mitochondria—the cell’s powerhouses—lie at the centre of this mystery. These tiny organelles generate most of the cell’s energy, but they also accumulate damage with age and are implicated in age-related diseases. Paradoxically, studies in multiple species reveal that reducing mitochondrial activity can actually extend lifespan. How can less energy make an organism live longer?
Our laboratory has recently resolved part of this paradox. Using Drosophila melanogaster, we discovered that flies are highly sensitive to mitochondrial dysfunction during development but remarkably resilient in adulthood. A mild (10%) reduction in mitochondrial function during larval or pupal stages can halve adult lifespan, whereas a severe (75%) reduction in adulthood has no detrimental effects—and can even promote longevity. These results suggest that mitochondria are not equally essential throughout life; instead, their timing of activity is what matters most.
Project Aim
This PhD will determine when mitochondria are essential for ensuring a long and healthy adult life. The student will investigate which developmental stages require optimal mitochondrial function and whether these “critical windows” vary between tissues such as brain, muscle, gut, and fat body. Understanding this timing will help redefine how we view mitochondrial ageing and could ultimately inform strategies to promote healthspan across species.
Approach and Training
The student will use advanced Drosophila genetics (GAL4/GAL80/ GeneSwitch and QF2/QS systems) to control mitochondrial activity precisely in time and space. They will learn to combine genetic, molecular, and physiological techniques, including:
- Generating and characterising new fly lines using RNAi and CRISPR/Cas9.
- Measuring mitochondrial respiration through high-resolution respirometry.
- Assessing lifespan and mortality through Gompertz modelling.
- Performing tissue-specific imaging (confocal microscopy, TUNEL assays).
- Analysing large transcriptomics and proteomics datasets.
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