One of the key aims of the BCRB is to better understand the mechanisms that tightly control the redox homeostasis of the cell under stress conditions. We are studying the mechanisms behind reactive oxygen species (ROS) 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 structural changes during electron transfer, and the discovery of new cellular pathways involved in redox homeostasis.
• A long-term objective of the Collet lab is to better understand the redox mechanisms that govern the assembly of the cell envelope and maintain its integrity during the cell cycle.
• 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 mission of the Van Breusegem lab is to study the impact and the molecular response of plants against increased Reactive Oxygen Species levels by employing multi-disciplinary omics-driven approaches.
The coming years we want to exploit our expertise in thiol/redox-biochemistry through the following projects:
• ‘Oxidative stress signaling, redox regulation and cysteine protection’
One of the warning messages used by living cells under stress is the production of 'Reactive Oxygen Species (ROS). Within proteins, cysteine and methionine residues are sensitive to oxidation by reactive oxygen species (ROS). The first oxidation product of cysteines to ROS is the sulfenic acid derivative, and a methionine is oxidized to a sulfoxide.
Sulfenylation and sulfoxydation modulates signal transduction pathways by altering the activity and function of cellular proteins. We want to identify new proteins and pathways regulated by these post translational modifications, and to understand how they are controlled at the cellular level.
• ‘ROS signaling gene networks in plants'
ROS have emerged as important regulators of plant stress responses. Perturbation in ROS production and/or scavenging are sensed by plant cells as a 'warning' message, and genetic programs leading to stress acclimation or cell death are switched on. Knowledge on regulatory events during ROS signal transduction is now only scratching the surface. Through combined top-down and bottom-up genomics and proteomics approaches the Van Breusegem and Messens labs are dissecting the gene network governing ROS signal transduction in plants and pinpoint genes that are potential candidates for innovative molecular breeding strategies to develop stress-tolerant crops.
• ‘Understanding the redox pathways involved in protein folding’
How proteins fold in the cell envelope is a long-standing mystery. Several protein folding catalysts and chaperones have been identified in the envelope, but how they assist protein folding is only partially understood. We and others have significantly contributed to the characterisation of the pathways that oxidatively fold envelope proteins in E. coli. We now want to address the intriguing problems that are still unsolved regarding the oxidative protein folding.
• ‘New redox pathways to fight tuberculosis’
Tuberculosis (TB), once referred to as the ‘‘white death’’, is a debilitating human disease caused by Mycobacterium tuberculosis (Mtb). One of the main aims of the Messens lab is to reveal new redox pathways involved in the oxidative stress defence of the bacterial pathogen Mycobacterium tuberculosis during persistence in human macrophages.
• ‘Discovering the molecular mechanisms activating the Rcs cascade’
In the Collet lab, we want to understand how the Rcs phosphorelay is activated. The Rcs pathway, which is one of the major envelope stress response systems in E. coli, controls the expression of genes involved in the protection of envelope integrity, in biofilm formation and in virulence-associated structures.