The mission of the Messens lab is to decipher redox-regulated protein-protein interactions in macromolecular complexes, with the ultimate goal to improve oxidative stress resistance in plants and to identify novel therapeutic targets in redox diseases.
The Achilles’ heel of oxidative stress survival of pathogenic Actinomycetes
||How proteins sense oxidation and transduce reactive oxygen stimuli into downstream biological effects is one of the major challenges in redox biology. Knowledge of the mechanisms by which these redox sensors and transducers function are invaluable in understanding how these pathways can be manipulated, thus opening up new possibilities for the discovery of new targets or treatments. We aim to pinpoint crucial protein switches and to understand the mechanistic on-and-off-processes in communication.|
Persistent human Actinomycete pathogens, like Mycobacterium tuberculosis, are dynamically being reprogrammed to survive H2O2 and HOCl (bleach) stress of our immune system. They engage various enzymatic strategies to fight off ROS and keep their intracellular redox state in homeostasis to prevent damage. A specific redox defense system in these bacteria is mycothiol (MSH), a low molecular weight (LMW) thiol molecule which serves as a glutathione (GSH) surrogate. MSH is critical for the oxidative stress defense of Actinomycetes, and we are unraveling the detailed mode of action of mycothiol electron transfer pathways of oxidative stress defense enzymes.Oxidative stress tolerance in plants
Biotic and abiotic stresses cause significant agricultural yield losses worldwide, and accumulation of reactive oxygen species (ROS) can both cause damage on cellular components, inducing cell death, and act as signal molecules. Knowledge of the redox checkpoints in its signaling network will be invaluable in understanding how these pathways can be manipulated. The objective is to analyze the dynamics in the thiol-proteome under oxidative stress and in function of time by identifying the proteins that are modified by ROS on their cysteines, and to understand the structure/function of sensor proteins in complex with their target proteins.Cancer: a redox disease
In cancer cells, high peroxide levels are dynamically outbalanced by up-regulated anti-oxidant systems, among which peroxiredoxins (Prx) play an important role. Prx are abundant and maintain the peroxide levels low, and Prx can act in redox relay complexes with other proteins. The transcription factor STAT3 is such an interacting protein, and it is aberrantly activated in numerous cancer cells, and promotes tumorigenesis. To bring the cancer cell out of balance, we will target specific regions involved in catalytic conformational change that trap Prx transducers in complex with their partner.