Redox metabolism research group

OUR SCIENCE: THE BASICS
OUR SCIENCE: THE DETAIL

OUR SCIENCE: THE BASICS

“Can we influence cell signalling to help combat diseases?”

Redox signalling is a critical process within the cell essential for key signalling pathways. It plays a part in gene expression, modulates a number of metabolic pathways and keeps the cell biochemically balanced.

When redox signalling is disrupted, it can cause issues for the cell and the organism as a whole. Dysregulation of redox signalling is linked to many age-related diseases, as well as the aging process itself.

We are working to better understand how redox signalling is controlled, as well as how it can be influenced by drugs and diet. We recently demonstrated that sugar-induced obesity and insulin resistance may not necessarily lead to a shortened lifespan, and could be balanced by an increased intake of water.

We use the fruit fly Drosophila as in vivo systems through which we conduct our research. We use a combination of biochemical and genetic approaches to find out more about the physiological importance of redox signalling.

For studies focussing the links between redox signalling and diet for example, we place Drosophila on different feeding regimes to study the changes in their metabolism.

Ultimately, our goal is to uncover novel pathways and potential therapeutic targets for health and longevity benefits, including combating obesity, insulin resistance, and even aging.

OUR SCIENCE: THE DETAIL

“Our research focuses on investigating the role of redox signalling in metabolism, disease and ageing.”

Redox signalling is an important modulator of diverse biomedically relevant metabolic pathways (Figure 1). Consequently, dysregulation of redox homeostasis is implicated in the pathophysiology of many age-related diseases, as well as in the ageing process itself. However, the underlying mechanisms remain largely unclear, which hampers the development of effective therapeutic strategies. To address this challenge, our group leverages the fruit fly Drosophila as a powerful and tractable in vivo system, with its combination of short lifespan and strong evolutionary conservation of central signalling pathways and druggable targets regulating energy metabolism and lifespan.

Figure 1: Redox signalling operates through the specific post-translational modification of key redox-sensitive cysteine residues on target proteins. This reversible ‘redox switch’ integrates signals from oxidative, nutritional and environmental cues to selectively regulate cellular function (Lennicke & Cochemé 2020, Biochem Soc Trans).

Our research is focused on the following complementary questions:

(1) How does redox signalling regulate metabolic homeostasis and ageing? We aim to identify, characterise and manipulate redox-sensitive targets using a combination of biochemical, proteomic and genetic knock-in approaches, in order to unravel the physiological importance of redox signalling in vivo in the context of metabolic diseases and ageing (e.g. van Leeuwen et al. 2017, Free Rad Biol Med; Cochemé* et al. 2019, BioRxiv).

(2) How do diets and drugs impact on survival? We perform dietary and drug interventions shedding light on the complex interplay between redox balance, metabolic dysfunction and ageing. For instance, we recently showed that sugar-induced obesity and insulin resistance can be uncoupled from shortened lifespan, and identified dysregulation of purine catabolism as underlying the pathophysiology of high sugar diets in Drosophila (Figure 2). Furthermore, we extended our study to humans, and found that the association between dietary sugar intake and circulating purines was conserved in a population cohort (van Dam et al. 2020, Cell Metab). We are also interested in exploring evolutionary conserved pharmacological interventions that extend lifespan (e.g. Pryor et al. 2019, Cell).

Ultimately, our goal is to uncover novel pathways and potential therapeutic targets for health and longevity benefits.