One of the key aims of the Joris Messens lab is to better understand the mechanisms that control redox and metabolite signaling of the cell. We are studying the mechanisms behind reactive oxygen species scavenging, signaling, and regulation. Several oxidoreductase proteins, which successively pass on electrons via complex intra- and intermolecular cascades using thiol-disulfide chemistry, are involved. We specialize in the in vitro reconstitution of these thiol/disulfide electron transfer pathways, the study of the kinetics and protein structural changes during electron transfer, and the design of new tools to study the crosstalk between redox and metabolite signaling.
The mission of the Messens lab is to decipher how cells communicate via H2O2 and metabolite signals and how cells transduce these messages into downstream biological effects.
In the coming years we want to fully employ our team’s dynamic expertise in redox biochemistry and biosensor development through the following projects:
The architecture of redox-relay signaling complexes: Determining the structural aspects that dictate selectivity of H2O2-signal driven protein-protein interactions
The molecular details of how H2O2 serves as a signaling molecule are still one big mystery. Human peroxiredoxins, initially described as H2O2 scavengers, have a high cellular abundance, and have been shown to play an important role in redox-relay signaling. Peroxiredoxins (Prdxs) can transfer H2O2-derived oxidative equivalents via a redox-relay to target proteins. While the chemistry is clear, it remains unclear how Prdxs recognize their target proteins as well as how Prdxs structurally position themselves for an effective oxidative transfer. The Joris Messens lab studies the overall composition and the organization of these complexes.
Molecular imaging tools based on protein conformational changes: Making the subcellular metabolite flux visible
To investigate intracellular signaling by metabolites, it is important to have proper tools to visualize their trafficking in real time in living cells at subcellular resolution, which current mass spectrometry “omics” methods cannot offer. In response to this need, we design protein-based biosensors. They consist of a transcription factor that, by nature, has evolved to be specific for a metabolite and into which we genetically introduce a fluorescent protein as read-out. The Joris Messens lab uses these biosensors in combination with the latest tools for H2O2 detection and manipulation to probe the crosstalk between H2O2 and metabolic pathways.