Organisms have internal clocks that regulate their metabolism, physiology and behaviour to occur at optimal times throughout the day. These internal clocks allow them not only to anticipate but also to respond to the challenges they face. As an experimental model, we focus on the fruit fly Drosophila melanogaster, which has sleep/wake cycles that deteriorate with age (as they do in humans). Our lab seeks to understand how brain clocks communicate with each other and with clocks in the rest of the body to stay synchronised. One such mechanism is the daily structural remodelling of their connectivity, which has revealed a degree of plasticity unexpected in the adult brain; dissecting the underlying molecular mechanisms could provide insights into the treatment of nervous system pathologies. Internal clocks also depend on complex molecular networks that integrate environmental and internal cues that are essential for maintaining homeostasis. We are investigating such integration between basal cellular metabolism and the molecular clock, and how its progressive dysfunction affects lifespan. To address this fundamental question, we are focusing on a gene essential for the regulation of lipid catabolism, whose dysfunction is associated with early developmental lethality.