The NADPH oxidase present in phagocytes functions to produce superoxide anions in a controlled manner, leading to the generation of reactive oxygen species (ROS). Its activity is essential for the innate immune system to fight infections and destroy pathogens sequestered within phagosomes. The enzyme’s membrane-bound subunits (Nox2, p22phox) and cytosolic subunits (p47phox, p67phox, p40phox, and Rac) are separated in resting cells and only assemble after activation of cellular signaling pathways, forming an active complex at the phagosome membrane. In this conformation, the enzyme can bind its substrate (NADPH) and facilitate transmembrane electron transfers. This spatial and temporal regulation prevents the uncontrolled generation of ROS, which could otherwise lead to harmful oxidative stress, damaging both the cells and surrounding tissues. This enzyme also plays a critical role in severe inflammatory pathologies and is currently a focus of therapeutic developments aimed at controlling its activity.

Three teams within the CPSysBio group focus on this theme:

• • • • • • • • Fluorescent Proteins and Biosensors for Imaging
              • Dynamics and Function of Redox Proteins and Oxidative Stress
              • Signaling in Phagocytes

To study these processes at different biological scales, from the molecular level to whole cells, we have developed a wide array of methods incorporating biochemistry, cellular biology, and biophysics. The NADPH oxidase theme is organized into five closely interconnected research areas:

• • • • • • • • Phagocytosis and Signaling
              • Phagocytes and Oxidative Stress
              • ROS Detection
              • Structure-Function Relationship, Membranes, and Complex Assembly
              • Reaction Mechanisms within NADPH Oxidase and Other Flavoenzymes