Ageing is one of the most important biomedical challenges humanity will confront during the 21st century. Our laboratory studies how and why we age and which role the cell's powerhouses (named mitochondria) play in ageing. Our final goal is to develop therapies to prevent, delay or reverse human ageing.
The accumulation of dysfunctional mitochondria that produce high levels of Reactive Oxygen Species (mtROS) is one of the few hallmarks of ageing conserved across evolution. We have learned the consequences of the pile-up of defective mitochondria, i.e., oxidative damage and disruption of redox signalling. However, we ignore how or why the former happens.
In the past, our laboratory has demonstrated that Drosophila melanogaster flies require mtROS signalling to adapt to stress correctly [1]. In response to stress, fly mitochondria produce high levels of mtROS for a short period [2]. Recently, we have shown that aged mitochondria lose the capacity to respond to stress with ROS signals, and instead, they produce continuously high levels of ROS [3]. This project aims to dissect how and why old mitochondria produce more ROS than young mitochondria in detail.
The student will work with the model organism Drosophila melanogaster in a project with two clear aims. Firstly, the student will investigate "how do old mitochondria produce more ROS"? The aim is to dissect how old mitochondria produce mtROS using a combination of hypothesis and non-hypothesis methods. Secondly, the student will interrogate, "why do old mitochondria produce more ROS"? Here the student will use state-of-the-art technology to modify the fly epigenome testing if this affects the way mitochondria produce ROS.
Techniques:
To complete the PhD, the student will learn different techniques and methods from various disciplines such as cell and molecular biology, bioinformatics, genetics and physiology. More importantly, the student will learn to generate relevant hypotheses in the field of ageing and test them using lifespan experiments taking advantage of the short lifespan of fruit flies.
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