Working Groups

  • WG1
  • WG2
  • WG3
  • WG4
  • WG5
  • WG6
SOURCES OF REACTIVE OXYGEN SPECIES (Leader: Ulla Knaus, Ireland) aims to identify physiological and disease-relevant molecular sources of ROS. This is done by using highly specific tools generated by WG3 (e.g. genetic animal models, siRNA, miRNA, antibodies, ROS detection methods) for assessing the contribution to ROS production and ROS degradation in different systems (e.g. isolated cells, single cell organisms, organs, animal models and plants). WG1 therefore assesses regulation of expression, sub-cellular localisation, activity and interactions of ROS and their sources. This reseach is essential to establish strategies that inhibit disease-relevant sources of ROS without eliminating physiological ROS formation.
MOLECULAR MECHANISMS AND TARGETS OF REACTIVE OXYGEN SPECIES (Leader: Agnes Görlach, Germany) aims to identify molecular mechanisms of ROS actions (redox signalling, direct chemical interactions) and their molecular targets. This will give insight into the role of altered ROS production and ROS signalling in initiation and progression of disease in single-cell organisms up to complex organisms. The results will also allow precise identification of molecular defects. EU-ROS will define ROS’ physiological roles and post-translational modifications as well as other changes such as molecular damage caused by oxidative and reductive stress.
DRUGS AND TOOLS (Leader: Tamara Seredenin, Switzerland) aims to design, synthesize and pharmacologically test novel inhibitors that selectively block ROS sources (see WG1) as well as serve as enhancers of beneficial ROS signalling pathways. At the same time, WG3 develops tools to enable comprehensive analysis for ROS sources and targets (e.g. genetic animal models, siRNA, miRNA, antibodies, ROS detection methods). These will be first applied for target validation in pre-clinical models. Later they will be used for drug development. Proof of concept of the modulators will be provided in models followed by pre-clinical development. EU-ROS will also develop principles for crop science. One major advantage of this COST Action is that its multifaceted approach allows pinpointing the best indications/applications for a given therapeutic target, as a drug candidate will be tested in various species and disease models available within EU-ROS. It will also give insight into side effects and indications to be avoided. Together, this enables a comprehensive evaluation of drug candidates. This is essential to develop a drug for the application(s) most likely to succeed in the clinics, or being applied for non-medical purposes e.g. agriculture.
DIAGNOSTICS AND BIOMARKERS FOR REACTIVE OXYGEN SPECIES (Leader: Pietro Ghezzi, United Kingdom) aims to identify patients at risk for diseases caused by a redox imbalance, i.e. patients who would benefit from ROS modulating treatments. WG4 also aims to tailor the therapy to an individual patient by drug monitoring enabled by developing e.g. gene expression profiling and proteomics as well as oxidative stress biomarkers. Currently used biomarkers and risk factors, in particular for cardiovascular disorders, are hardly causal, but rather surrogate parameters and not suitable for drug monitoring. Therefore, novel biomarkers and their patterns are urgently needed to reliably assess the individual redox status and disease risk. Such novel diagnostics are of major clinical importance to identify patients at risk before symptoms become apparent and to monitor the success of therapies. EU-ROS’ bottom-up-approach also enables identifying novel candidate therapeutic redox targets that will feed into the other WGs. Finally, this work package will aid the validation of animal models to their suitability of studying human pathologies, i.e. weather they share identical pathomechanisms, a so far neglected area.
IMAGING (Leader: Yves Frappart, France) aims to localize ROS-triggered physiology and disease processes by developing and applying highly innovative imaging techniques using new modalities (electron paramagnetic resonance, Overhauser-enhanced MRI, near infrared imaging) and new contrast agents. Indeed, research on the redox biology is hampered by the difficulty to quantify and localise ROS. EU-ROS participants have recently provided e.g. progress by developing the first genetically encoded sensor for H2O2. Other members have been the first to couple electron paramagnetic resonance (EPR) to micro-computed tomography, which allows 3-D visualisation and overlay of the EPR image to anatomy, e.g. CT. The work of WG5 will help to define relevant sources of ROS (WG1) and novel biomarkers (WG4).
TECHNOLOGY TRANSFER AND FUNDING (Leader: Vincent Jaquet, Switzerland) aims to facilitate collaboration and success of R&D within EU-ROS by exchange of and assisting with protocols/SOPs, technologies, methods, samples, tools and models. In addition, WG6 coordinates and facilitates joint grant applications with participation from EU-ROS members.

EU-ROS’ WGs are strongly linked and integrated. Indeed, the objectives of each WG can only be achieved through continuous exchange of information and materials. Therefore, WG6 enables optimal transfer (e.g. by staff exchange and Training Schools) and joint use by participating groups to the benefit of all EU-ROS members. EU-ROS will for example organise multi-centre, pre-clinical studies to test drug candidates and validate animal models at different member labs. This will increase the likelihood of successful translation into the clinics and reduce the costs of drop out. Indeed, nowadays too many drug candidates fail in clinical developments, and this is – amongst obvious reasons e.g. inherited differences between human and animals – caused by insufficient quality of preclinical research. WG6 therefore implements and control quality issues for its scientific activities, such as SOPs.