Regulating the redox conditions withn the mammalian endoplasmic reticulum (360G-Wellcome-088053_Z_08_A)

The proposed research will address three specific areas. Firstly we will determine how oxidative stress within the endoplasmic reticulum (ER) is regulated. Here we will focus on how the activity of the ER oxidases that are potentially responsible for the production of reactive oxygen species in the ER are regulated. Our goal will be to fully understand their mechanism of action so that we can predict how they contribute to oxidative stress. Secondly we will characterise the role of ER enzyme s in protecting the cell from alterations in redox status and ER-generated ROS. Our goal will be to identify and characterise key components that prevent excessive oxidative stress. Finally we aim to identify novel components that are involved in regulating the levels of the redox buffer within the ER and in sensing ER generated oxidative stress. Here our goal will be to develop methodologies to monitor cellular redox status and to use these tools to identify cellular proteins whose function is to maintain redox homeostasis.