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 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 signaling.
• 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 how cells sense redox metabolites and transduce stimuli into downstream biological effects.
• The mission of the Van Breusegem lab is to study the impact and the molecular response of plants against increased Reactive Oxygen Species levels.
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.
• ‘Redox signaling networks in plants'
ROS has emerged as important regulator 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 hydrogen peroxide 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 network governing H2O2 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.
• ‘Cancer a redox disease’
Redox metabolism is central to cancer progression. Cancer cells are known to produce more reactive oxygen species, but at the same time are more sensitive to oxidative stress compared to normal cells. During metastasis, cancer cells dramatically change their cellular redox environment. To survive these changes, cancer cells develop effective protection mechanisms that aid adaptation to various types of environmental conditions. As such, many cancers express high amounts of antioxidant enzymes, such as the peroxiredoxins (Prxs). Prxs are highly efficient peroxide scavenging enzymes, and recently it has been shown that Prxs are also able to transfer the peroxide signal to the less reactive regulatory proteins. One of the long-term objectives of the Messens lab is to explore and eventually manipulate the protein scaffolding system which supports Prx-mediated peroxide signalling, and to develop sensitive protein-based redox and metabolite indicator tools.
• ‘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.