Molecular basis of the oxidative stress response and its regulation

Reactive oxygen species (ROS) are obligatory by-products of aerobic living conditions and important signalling molecules. Excessive amounts of ROS can be deleterious for cells: they can damage proteins, membranes and the DNA. They are the cause and consequence of multiple human diseases. Complex pathways have evolved to maintain the redox balance and, if necessary, trigger apoptosis to protect cells from damage accumulation. Despite their importance in human health and disease, the molecular mechanisms of ROS-regulated gene expression and cell survival decisions under oxidative conditions are poorly understood, with several key questions remaining. What are the molecular mechanisms underlying redox stress response in higher eukaryotes? What are the safety mechanisms that protect cells from thriving under oxidative stress and how are these mechanisms hijacked in pathological conditions? To answer these questions, I will elucidate the key steps in the redox stress response using a combination of biophysical and structural techniques. This work will focus on: i) the regulation of the major transcription factor implicated in the redox stress response; ii) the activation of the detoxification machinery; iii) the safety mechanisms that govern cell fate under oxidative stress.